WO2024182715A1 - Heterocyclics as egfr inhibitors - Google Patents

Abstract

The present application relates to EGFR inhibitor compounds of Formula (I), as defined herein, and pharmaceutically acceptable salts thereof. The present application also describes pharmaceutical composition comprising a compound of Formula (I), and pharmaceutically acceptable salts thereof, and methods of using the compounds and compositions for inhibiting certain protein-protein interactions, and for treating cancer.

Description

HETEROCYCLICS AS EGFR INHIBITORS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application No.63/488,147, filed March 2, 2023, which is incorporated by reference herein in its entirety. TECHNICAL FIELD [0002] The present application relates to heterocyclic compounds that are useful for treating proliferative disorders such as cancer. BACKGROUND OF THE INVENTION [0003] The epidermal growth factor receptor (EGFR) is a transmembrane receptor that can transduce mitogenic signaling. Upon binding of extracellular protein ligands, such as EGF and EGF family members, EGFR undergoes a conformational change, leading to homo or heterodimerization, stimulation of its intrinsic tyrosine kinase activity, autophosphorylation of several tyrosine residues in its intracellular domain, and signal transduction of MAPK/ERK, AKT, and JNK pathways. Ultimately, induction of these pathways can lead to DNA synthesis, cell proliferation, and cell migration (Normano et al., Gene 366(1):2-16 (2006)). [0004] Mutations in the EGFR gene are found in approximately 15-40% of non-small cell lung cancer (NSCLC) and of those, 80% lead to either a short in-frame deletion of exon 19 (Del19) or a single missense mutation in exon 21, L858R (Midha et al., Am J Cancer Res 15;5(9):2892-911 (2015)). Both of these mutations lead to ligand-independent EGFR activation, driving tumor survival and proliferation. While treatment of patients with first and second-generation EGFR inhibitors, such as erlotinib, gefitinib, and afatinib, can lead to a marked tumor regression, this response is short-lived. Most treated patients (50-70%) experience disease progression with the acquisition of T790M, a gatekeeper mutation with increased affinity for ATP (Blakely et al., Cancer Discov 2(10):872-5 (2012)). [0005] Osimertinib, a third-generation EGFR inhibitor, overcomes T790M-driven resistance while maintaining efficacy against Del19 or L858R driver mutations (Mok et al., N Engl J Med 376:629-640 (2017)). Relative to earlier EGFR inhibitors, osimertinib has several notable characteristics: 1) greater selectivity for mutants over WT EGFR; 2) lower rates and severity of gastrointestinal and dermatological toxicities; and 3) efficacy against brain metastases owing to CNS exposure. These features led to FDA approval for T790M mutation-positive NSCLC in 2015 and approval as a first line treatment of EGFR- mutant NSCLC in 2018 (Ramalingam et al., N Engl J Med 382(1):41-50 (2020)). [0006] While osimertinib demonstrates clear clinical efficacy, new on-target resistance mechanisms have emerged in response to treatment with the third generation inhibitor. In particular, the C797S mutation - which prevents osimertinib from forming a covalent bond with a cysteine residue in the binding site - has been observed in patients treated with osimertinib. In relapsed patients that developed the T790M mutation before treatment with osimertinib, 22-40% of patients developed this resistance mutation (Madic et al., Oncotarget 9(100):37393-37406 (2018)). In patients treated with osimertinib in the first line, 7% of patients have been reported to develop the C797S mutation (Leonetti et al., Br J Cancer 21(9):725-737 (2019)). [0007] Thus, on-target resistance to osimertinib through the EGFR C797S mutation has been observed on its own in patients treated with osimertinib in the first line and in combination with T790M in patients who have progressed after sequential treatment with first generation inhibitors and osimertinib. First generation EGFR compounds retain activity against the C797S mutation in the absence of T790M and have been combined with osimertinib to treat patients who develop T790M and C797S mutations in trans after sequential treatment with first generation and third generation inhibitors (Arunalananda et al., J Thorac Oncol 12(11):1728-1732 (2017)). However, first generation EGFR compounds exhibit poor CNS penetrance, enabling the development of CNS metastases, and only achieve modest selectivity over WT EGFR, which limits their tolerability and utility in combination with other agents. Zorifertinib, which has activity against mutant EGFR and can penetrate the blood brain barrier, is under evaluation in patients with advanced EGFR mutation positive NSCLC with CNS metastasis. However, this compound achieves only modest (<10-fold) mutant EGFR selectivity and has demonstrated high rates of gastrointestinal and skin toxicities associated with inhibition of WT EGFR (Yang et al., Oncotarget.7:78985-78993 (2016); Ahn et al., Lancet Respir Med 5(11):891-902 (2017)). Thus, there is a need to develop brain penetrant compounds that are active against EGFR activating mutations (Del-19 or L858R), spare EGFR WT, and retain activity in the presence of the C797S mutation. BRIEF SUMMARY OF THE INVENTION [0008] It has now been found that certain polycyclic heteroaromatic compounds can function as small-molecule tyrosine kinase inhibitors (e.g., inhibitors of EGFR activity), and are useful for treating various diseases and disorders, such as cancers. [0009] Accordingly, provided herein is a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein Ring A, R¹, R², R³, R⁴, R⁵ R⁶, R⁷, R⁸, R⁹, n and X are as defined herein. [0010] Also provided herein is a pharmaceutical composition including a compound of the invention, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. [0011] Also provided herein is a method of inhibiting mammalian cell proliferation, in vitro or in vivo, including contacting a cell with an effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as defined herein. [0012] Also provided herein is a method of treating cancer in a subject in need of such treatment, including administering to the subject an effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as defined herein. [0013] Other features and advantages of the invention will be apparent from the following detailed description and figures, and from the claims. DETAILED DESCRIPTION OF THE INVENTION I. GENERAL [0014] The present application provides chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit epidermal growth factor receptor (EGFR, ERBB1). These chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) EGFR activation contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). The present application also provides compositions containing the same, as well as methods of using and making the same. II. DEFINITIONS A. General Definitions [0015] Before the present invention is further described, it is to be understood that this invention is not strictly limited to particular embodiments described, as such may of course vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the claims. [0016] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, the preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates, which may need to be independently confirmed. [0017] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination. All combinations of the embodiments are specifically embraced by the present invention and are disclosed herein just as if each and every combination was individually and explicitly disclosed. In addition, all sub-combinations are also specifically embraced by the present invention and are disclosed herein just as if each and every such sub-combination was individually and explicitly disclosed herein. [0018] When ranges of number values are disclosed, and the notation “from n₁... to n₂” is used, where n₁ and n₂ are the numbers, then unless otherwise specified, this notation is intended to include the numbers themselves and the range between them. This range may be integral or continuous between and including the end values. By way of example, the range “from 2 to 6 carbons” is intended to include two, three, four, five, and six carbons, since carbons come in integer units. Compare, by way of example, the range “from 1 to 3 ^M (micromolar),” which is intended to include 1 ^M, 3 ^M, and everything in between to any number of significant figures (e.g., 1.255 ^M, 2.1 ^M, 2.9999 ^M, etc.). [0019] The term “about,” as used herein, is intended to qualify the numerical values that it modifies, denoting such a value as variable within a margin of error. When no particular margin of error, such as a standard deviation to a mean value given in a chart or table of data, is recited, the term “about” should be understood to mean that range which would encompass the recited value and the range which would be included by rounding up or down to that figure, taking into account significant figures. [0020] “A,” “an,” or “the” as used herein not only include aspects with one member, but also include aspects with more than one member. For instance, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a cell” includes a plurality of such cells and reference to “the agent” includes reference to one or more agents known to those skilled in the art, and so forth. B. Chemical Definitions [0021] The following chemical functional group definitions are provided to give guidance in understanding their meaning and scope. Those skilled in the art will recognize that these functional groups are being used in a manner consistent with practice of the chemical arts. Any of the following chemical functional groups may be optionally substituted as defined below and each chemical functional group below may itself be an optional substitution. [0022] As used herein, the term “compounds of the invention” refers to the compounds of formula (I), and all of the embodiments thereof as described herein (e.g. compounds of formulae (I-A), (I-B), and (I-C)), and to the compounds identified in Table A, Table B, and the Examples. [0023] The term “alkyl” as used herein, alone or in combination, (sometimes abbreviated Alk) refers to a straight-chain or branched-chain alkyl radical containing from 1 to 20 carbon atoms. In certain embodiments, the alkyl may comprise from 1 to 10 carbon atoms. In further embodiments, the alkyl may comprise from 1 to 6 carbon atoms, or from 1 to 4 carbon atoms. Unless otherwise specified, alkyl can include any number of carbons, such as C₁, C₁-C₂, C₁-C₃, C₁-C₄, C₁-C₅, C₁-C₆, C₁-C₇, C₁-C₈, C₁-C₉, C₁-C₁₀, C₂, C₂-C₃, C₂-C₄, C₂-C₅, C₂-C₆, C₃, C₃-C₄, C₃-C₅, C₃-C₆, C₄, C₄-C₅, C₄-C_6,, C₅, and C₅-C₆. For example, C₁-C₆ alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secbutyl, tertbutyl, pentyl, isopentyl, hexyl, etc. Alkyl can also refer to alkyl groups having up to 20 carbons atoms, such as, but not limited to heptyl, octyl, nonyl, decyl, etc. Alkyl groups can be substituted or unsubstituted. The term “alkylene,” as used herein, alone or in combination, refers to a saturated aliphatic group derived from a straight or branched chain saturated hydrocarbon attached at two or more positions, such as methylene (–CH₂–). Unless otherwise specified, the term “alkyl” may include “alkylene” groups. When the alkyl is methyl, it may be represented structurally as CH₃, Me, or just a single bond terminating with no end group substitution. [0024] The term “alkenyl” as used herein, alone or in combination, refers to a straight-chain or branched-chain hydrocarbon radical having one or more double bonds and containing from 2 to 20 carbon atoms. In certain embodiments, the alkenyl may comprise from 2 to 6 carbon atoms, or from 2 to 4 carbons, either of which may be referred to as “lower alkenyl.” The term “alkenylene” refers to a carbon-carbon double bond system attached at two or more positions such as ethenylene (–CH=CH–). Alkenyl can include any number of carbons, such as C₂, C₂-C₃, C₂-C₄, C₂-C₅, C₂-C₆, C₂-C₇, C₂-C₈, C₂-C₉, C₂-C₁₀, C₃, C₃-C₄, C₃-C₅, C₃-C₆, C₄, C₄-C₅, C₄-C₆, C₅, C₅-C₆, C₆, and so on up to 20 carbon atoms. Alkenyl groups can have any suitable number of double bonds, including, but not limited to, 1, 2, 3, 4, 5 or more. Examples of alkenyl groups include, but are not limited to, vinyl (ethenyl), propenyl, isopropenyl, 1-butenyl, 2-butenyl, isobutenyl, butadienyl, 1pentenyl, 2-pentenyl, isopentenyl, 1,3-pentadienyl, 1,4-pentadienyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 1,3-hexadienyl, 1,4-hexadienyl, 1,5-hexadienyl, 2,4-hexadienyl, or 1,3,5-hexatrienyl. Alkenyl groups can be substituted or unsubstituted. Unless otherwise specified, the term “alkenyl” may include “alkenylene” groups. [0025] The term “alkynyl” as used herein, alone or in combination, refers to a straight-chain or branched-chain hydrocarbon radical having one or more triple bonds and containing from 2 to 20 carbon atoms. In certain embodiments, the alkenyl may comprise from 2 to 6 carbon atoms, or from 2 to 4 carbons, either of which may be referred to as “lower alkynyl.” Alkynyl can include any number of carbons, such as C₂, C₃, C₄, C₅, C₆, C₇, C₈, C₉, C₁₀, C₁₁, C₁₂, C₁₃, C₁₄, C₁₅, C₁₆, C₁₇, C₁₈, C₁₉, and C₂₀. Alkenyl groups can have any suitable number of triple bonds, including, but not limited to, 1, 2, 3, 4, 5 or more. Examples of alkynyl groups include, but are not limited to, ethynyl. Alkynyl groups can be substituted or unsubstituted. Unless otherwise specified, the term “alkynyl” may include “alkynylene” groups. [0026] The term “alkoxy” as used herein, alone or in combination, refers to an alkyl ether radical, wherein the term alkyl is as defined below. Alkoxy groups may have the general formula: –O-alkyl. As for alkyl group, alkoxy groups can have any suitable number of carbon atoms, such as C_1-6. Alkoxy groups include, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, 2-butoxy, isobutoxy, secbutoxy, tertbutoxy, pentoxy, hexoxy, and the like. The alkoxy groups can be further optionally substituted as defined herein. [0027] The term “halo” or “halogen” as used herein, alone, or in combination, refers to fluorine, chlorine, bromine, or iodine. [0028] The term “haloalkyl” as used herein, alone or in combination, refers to an alkyl radical having the meaning as defined above wherein one or more hydrogens are replaced with a halogen. Specifically embraced are monohaloalkyl, dihaloalkyl, trihaloalkyl, and polyhaloalkyl radicals. A monohaloalkyl radical, for one example, may have an iodo, bromo, chloro, or fluoro atom within the radical. Dihalo and polyhaloalkyl radicals may have two or more of the same halo atoms or a combination of different halo radicals. Examples of haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, and dichloropropyl. “Haloalkylene” refers to a haloalkyl group attached at two or more positions. Examples include fluoromethylene (–CFH–), difluoromethylene (–CF₂–), chloromethylene (–CHCl–), and the like. [0029] The term “heteroalkyl” as used herein, alone or in combination, refers to a stable straight or branched chain, or cyclic hydrocarbon radical, or combinations thereof, fully saturated or containing from 1 to 3 degrees of unsaturation, consisting of the stated number of carbon atoms and from one to three heteroatoms selected from the group consisting of O, N, and S, and wherein the nitrogen and sulfur atoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized (i.e. bond to 4 groups). The heteroatom(s) O, N, and S may be placed at any interior position of the heteroalkyl group. Up to two heteroatoms may be consecutive, such as, for example, –CH₂NHOCH₃. The term heteroalkyl may include ethers. [0030] The term “hydroxy” as used herein, alone or in combination, refers to OH. [0031] The term “hydroxyalkyl” as used herein, alone or in combination, refers to a hydroxy group attached to the parent molecular moiety through an alkyl group. “Hydroxyalkyl” or “alkylhydroxy” refers to an alkyl group, as defined above, where at least one of the hydrogen atoms is replaced with a hydroxy group. As for the alkyl group, hydroxyalkyl or alkylhydroxy groups can have any suitable number of carbon atoms, such as C₁-₆. Exemplary C_1-4 hydroxyalkyl groups include, but are not limited to, hydroxymethyl, hydroxyethyl (where the hydroxy is in the 1 or 2 position), hydroxypropyl (where the hydroxy is in the 1, 2 or 3 position), hydroxybutyl (where the hydroxy is in the 1, 2, 3 or 4 position), 1,2-dihydroxyethyl, and the like. [0032] The term “cyanoalkyl” as used herein, alone or in combination, refers to a cyano group (–CN) attached to the parent molecular moiety through an alkyl group. “Cyanoalkyl” or “alkylcyano” refers to an alkyl group, as defined above, where at least one of the hydrogen atoms is replaced with a cyano group. As for the alkyl group, cyanoalkyl or alkylcyano groups can have any suitable number of carbon atoms, such as C₁-₆ or C₁-C₃. Exemplary C_1-4 cyanoalkyl groups include, but are not limited to, cyanomethyl, cyanoethyl (where the cyano group is in the 1 or 2 position), cyanopropyl (where the cyano group is in the 1, 2 or 3 position), cyanobutyl (where the cyano group is in the 1, 2, 3 or 4 position), and the like. [0033] As used herein, the term “cycloalkyl” refers to a saturated or partially unsaturated mono- or bicyclic carbon group having 3 to 10 carbon atoms, such as C₃-C₁₀ cycloalkyl groups and C₃-C₆ cycloalkyl groups. Bicyclic cycloalkyl groups include fused, spiro, and bridged ring systems. Non-limiting examples of cycloalkyl groups include phenyl, 2,3-dihydro-1H-indene, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[2.3]hexyl, spiro[3.3]heptanyl, and bicyclo[1.1.1]pentyl, bicyclo[2.2.1]heptyl, and spiro[2.5]octyl. [0034] The term “heterocyclyl” refers to a saturated or partially unsaturated hydrocarbon monocyclic or bicyclic ring system, having 3 to 10 ring atoms, that is not aromatic, having at least one heteroatom within the ring selected from N, O, and S. Bicyclic heterocyclyl groups include fused, spiro, and bridged ring systems. The heterocyclyl group may be denoted as, for example, a “5 to 10-membered heterocyclyl group,” which is a ring system containing 5, 6, 7, 8, 9 or 10 atoms at least one being a heteroatom. Heterocyclyl groups can, for example, have 1, 2, 3, or more, heteroatoms. In some embodiments, a heterocyclyl group has one or two independently selected heteroatoms. A heterocycle may further contain one or more carbonyl or thiocarbonyl functionalities, so as to make the definition include oxo- systems and thio- systems such as lactams, lactones, cyclic imides, cyclic thioimides, and cyclic carbamates. The heterocyclyl group may be bonded to the rest of the molecule through any carbon atom or through a heteroatom such as nitrogen. Exemplary heterocyclyl groups include, but are not limited to azepanyl, 1,3-dioxolane, 1,4-dioxolanyl, maleimidyl, succinimidyl, dioxopiperazinyl, hydantoinyl, imidazolinyl, imidazolidinyl, isoxazolinyl, isoxazolidinyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolinyl, thiazolidinyl, morpholinyl, oxiranyl, piperidinyl N-oxide, piperidinyl, piperazinyl, pyrrolidinyl, pyrrolidonyl, pyrrolidionyl, 4-piperidonyl, pyrazolinyl, pyrazolidinyl, 2-oxopyrrolidinyl, tetrahydropyranyl, quinuclidineyl, 4H-pyranyl, azetidinyl, oxetanyl, octahydrocyclopenta[c]pyrrole, 2-azaspiro[3.3]heptanyl, 3-oxabicyclo[3.1.0]hexanyl, 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[3.1.1]heptanyl, 4-azaspiro[2.5]octanyl, 6-azaspiro[3.5]nonanyl, 2,6-diazaspiro[3.3]heptanyl, 7-azabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]heptanyl, 2,5-diazabicyclo[2.2.2]octanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 2-oxabicyclo[2.1.1]hexanyl, 3-azabicyclo[3.2.1]octanyl, hexahydro-1H-cyclopenta[c]pyrrolyl, 3-oxa-9-azabicyclo[3.3.1]nonanyl, and hexahydro-1H-pyrrolizinyl. [0035] The term “aryl” as used herein, alone or in combination, refers to a hydrocarbon ring system radical comprising hydrogen, 6 to 18 carbon atoms and at least one aromatic ring. Exemplary aryls are hydrocarbon ring system radical comprising hydrogen and 6 to 10 carbon atoms and at least one aromatic ring; hydrocarbon ring system radical comprising hydrogen and 9 to 12 carbon atoms and at least one aromatic ring; hydrocarbon ring system radical comprising hydrogen and 12 to 15 carbon atoms and at least one aromatic ring; or hydrocarbon ring system radical comprising hydrogen and 15 to 18 carbon atoms and at least one aromatic ring. For purposes of this invention, the aryl radical may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused or bridged ring systems. Aryl radicals include, but are not limited to, aryl radicals derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as-indacene, s-indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene. [0036] As used herein, the term “heteroaryl” refers to a 5- to 10-membered mono- or bicyclic group wherein at least one ring in the system is aromatic; and wherein one or more carbon atoms in at least one ring in the system is/are replaced with an heteroatom independently selected from N, O, and S. Non-limiting examples of heteroaryl groups include furanyl, furazanyl, thiofuranyl, benzothiophenyl, phthalazinyl, pyrrolyl, oxazolyl, benzoxazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazole, thiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, benzothiazolyl, imidazolyl, benzimidazolyl, indolyl, indazole, pyrazolyl, benzopyrazolyl, isoxazolyl, benzoisoxazole, isothiazolyl, triazolyl, benzotriazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, purinyl, pteridinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, cinnolinyl, triazinyl, 2,3-dihydrobenzofuranyl, and 5,6,7,8-tetrahydroimidazo[1,5]pyridinyl. [0037] As used herein, when a ring is described as being “partially unsaturated”, it means said ring has one or more additional degrees of unsaturation (in addition to the degree of unsaturation attributed to the ring itself; e.g., one or more double or triple bonds between constituent ring atoms), provided that the ring is not aromatic. Examples of such rings include cyclopentene, cyclohexene, cycloheptene, dihydropyridine, tetrahydropyridine, dihydropyrrole, dihydrofuran, dihydrothiophene, and the like. [0038] As used herein, the term “spirocycle” refers to a direct attachment of a ring, including for example a carbocycle, heterocycle, aromatic and heteroaromatic ring, to a single carbon atom of the rest of the molecule, where the carbon at the point of attachment is part of the ring. Spirocyclic moieties include, for example, spirocyclic cycloalkyls (e.g., cyclobutane, cyclopentane, cyclohexane, etc.), spirocyclic dioxane, spirocyclic dioxolane, spirocyclic methylpyrrolidin-2-one, spyrocyclic 3-methyl-4,5-dihydroisoxazole, and spirocyclic tetrahydrofuran. [0039] The term “cyano” as used herein, alone or in combination, refers to –CN. [0040] The terms “oxy” or “oxa” as used herein, alone or in combination, refer to –O–. [0041] The term “oxo” as used herein, alone or in combination, refers to =O. [0042] In embodiments of the invention, any one of the positions that is understood to have a hydrogen may also exist or understood to be isotopically enriched. In the compounds of this invention, any atom not specifically designated as a particular isotope is meant to represent any stable isotope of that atom. Obtaining 100% deuteration at any relevant site of a compound in an amount of milligram or greater can be difficult. Therefore, it is understood that some percentage of hydrogen may still be present, even though a deuterium atom is specifically shown in a chemical structure. Thus, when a chemical structure contains a “D,” the compound represented by the structure is deuterium-enriched at the site represented by “D.” Unless otherwise stated, when a position is designated specifically as “H” or “hydrogen,” the position is understood to have hydrogen at its natural abundance isotopic composition. Also unless otherwise stated, when a position is designated specifically as “D” or “deuterium,” the position is understood to have deuterium at an abundance that is at least 3340 times greater than the natural abundance of deuterium, which is 0.015% (i.e., the term “D” or “deuterium” indicates at least 50.1% incorporation of deuterium). In embodiments, a benzene ring may be optionally exist as –C₆D₅, –C₆DH₄, –C₆D₂H₃, –C₆D₃H₂, and –C₆D₄H. In embodiments, a cyclohexyl group may optionally exist as –C₆D₁₁. [0043] Any definition herein may be used in combination with any other definition to describe a composite structural group. By convention, the trailing element of any such definition is that which attaches to the parent moiety. For example, the composite group alkylamido would represent an alkyl group attached to the parent molecule through an amido group, and the term alkoxyalkyl would represent an alkoxy group attached to the parent molecule through an alkyl group. [0044] The term “optionally substituted” means the anteceding group or groups may be substituted or unsubstituted. Groups constituting optional substitution may themselves be optionally substituted. For example, where an alkyl group is embraced by an optional substitution, that alkyl group itself may also be optionally substituted. When substituted, the substituents of an “optionally substituted” group may include, without limitation, one or more substituents independently selected from the following groups or a particular designated set of groups, alone or in combination: alkyl, alkenyl, alkynyl, alkanoyl, heteroalkyl, heterocycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, lower perhaloalkyl, perhaloalkoxy, cycloalkyl, phenyl, aryl, aryloxy, alkoxy, haloalkoxy, oxo, acyloxy, carbonyl, carboxyl, alkylcarbonyl, carboxyester, carboxamido, cyano, hydrogen, halogen, hydroxy, amino, alkylamino, arylamino, amido, sulfonamido, thioamido, nitro, thiol, alkylthio, haloalkylthio, perhaloalkylthio, arylthio, sulfonate, sulfonic acid, trisubstituted silyl, N₃, SH, SCH₃, C(O)CH₃, CO₂CH₃, CO₂H, pyridinyl, thiophene, furanyl, carbamate, thiocarbamate, thiourea, and urea. Particular subsets of optional substitution include, without limitation: (1) alkyl, halo, and alkoxy; (2) alkyl and halo; (3) alkyl and alkoxy; (4) alkyl, aryl, and heteroaryl; (5) halo and alkoxy; and (6) hydroxyl, alkyl, halo, alkoxy, and cyano. Where an optional substitution includes a heteroatom-hydrogen bond (–NH-, SH, OH), further optional substitution of the heteroatom hydrogen is contemplated and includes, without limitation optional substitution with alkyl, acyl, alkoxymethyl, alkoxyethyl, arylsulfonyl, alkyl sulfonyl, arylsulfoximinyl, alkylsulfoximinyl, any of which are further optionally substituted. These subsets of optional substitutions are intended to be merely exemplary and any combination of 2 to 5, or 2 to 10, or 2 to 20 of the groups recited above up to all the group recited above and any subrange in between are contemplated. “Optionally substituted” may include any of the chemical functional groups defined hereinabove and throughout this disclosure. Two optional substituents may be joined together to form a fused five-, six-, or seven-membered carbocyclic or heterocyclic ring consisting of zero to three heteroatoms, for example forming methylenedioxy or ethylenedioxy. An optionally substituted group may be unsubstituted (e.g., –CH₂CH₃), fully substituted (e.g., –CF₂CF₃), monosubstituted (e.g., –CH₂CH₂F) or substituted at a level anywhere in-between fully substituted and monosubstituted (e.g., –CH₂CF₃). [0045] The various optional substitutions need not be the same and any combination of optional substituent groups may be combined. For example, a carbon chain may be substituted with an alkyl group, a halo group, and an alkoxy group. Where substituents are recited without qualification as to substitution, both substituted and unsubstituted forms are encompassed. Where a substituent is qualified as “substituted,” the substituted form is specifically intended. Additionally, different sets of optional substituents to a particular moiety may be defined as needed; in these cases, the optional substitution will be as defined, often immediately following the phrase, “optionally substituted with.” [0046] Asymmetric centers, axial asymmetry (non-interchanging rotamers), or the like may exist in the compounds of the various embodiments disclosed herein. Such chirality may be designated by the symbols “R” or “S,” depending on the configuration of substituents around the chiral carbon atom or the relevant axis. It should be understood that embodiments encompasses all stereochemical isomeric forms, including diastereomeric, enantiomeric, and epimeric forms, d-isomers and l-isomers, and mixtures thereof. Individual stereoisomers of compounds can be prepared synthetically from commercially available starting materials which contain chiral centers or by preparation of mixtures of enantiomeric products followed by separation such as conversion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, direct separation of enantiomers on chiral chromatographic columns, or any other appropriate method known in the art. Starting compounds of particular stereochemistry are either commercially available or can be made and resolved by techniques known in the art. Additionally, the compounds of the various embodiments disclosed herein may exist as geometric isomers. The various embodiments disclosed herein includes all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the appropriate mixtures thereof. Additionally, compounds may exist as tautomers, including keto-enol tautomers; all tautomeric isomers are embraced by the embodiments disclosed herein. [0047] Additionally, the compounds of the various embodiments disclosed herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the various embodiments disclosed herein. [0048] Compounds provided herein may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. That is, an atom, in particular when mentioned in relation to a compound of the invention, includes all isotopes and isotopic mixtures of that atom, either naturally occurring or synthetically produced, either with natural abundance or in an isotopically enriched form. For example, when hydrogen is mentioned, it is understood to refer to ¹H, ²H, ³H or mixtures thereof; when carbon is mentioned, it is understood to refer to ¹¹C, ¹²C, ¹³C, ¹⁴C or mixtures thereof; when nitrogen is mentioned, it is understood to refer to ¹³N, ¹⁴N, ¹⁵N or mixtures thereof; when oxygen is mentioned, it is understood to refer to ¹⁴O, ¹⁵O, ¹⁶O, ¹⁷O, ¹⁸O or mixtures thereof; and when fluoro is mentioned, it is understood to refer to ¹⁸F, ¹⁹F or mixtures thereof; unless expressly noted otherwise. For example, in deuteroalkyl and deuteroalkoxy groups, where one or more hydrogen atoms are specifically replaced with deuterium (²H). As some of the aforementioned isotopes are radioactive, the compounds provided herein therefore also comprise compounds with one or more isotopes of one or more atoms, and mixtures thereof, including radioactive compounds, wherein one or more non-radioactive atoms has been replaced by one of its radioactive enriched isotopes. Radiolabeled compounds are useful as therapeutic agents, e.g., cancer therapeutic agents, research reagents, e.g., assay reagents, and diagnostic agents, e.g., in vivo imaging agents. All isotopic variations of the compounds provided herein, whether radioactive or not, are intended to be encompassed within the scope of the present invention. Salts and Prodrugs of Compounds [0049] Unless stated otherwise, any reference to a compound of formula (I) in connection with the invention should be understood to include the tautomers, racemates, and stereoisomers (e.g.atropisomers, enantiomers, diastereomers, etc. and mixtures of any of the foregoing) thereof, if any. In some embodiments, the invention relates to pharmaceutically acceptable salts, solvates, hydrates, polymorphs, physiologically functional derivatives (e.g. deuterated forms), metabolites, and/or prodrugs of a compound of formula (I). [0050] The compounds disclosed herein can exist as pharmaceutically acceptable salts, including acid addition salts. Suitable salts include those formed with both organic and inorganic acids. Such acid addition salts will normally be pharmaceutically acceptable. However, salts of non-pharmaceutically acceptable salts may be of utility in the preparation and purification of the compound in question. Basic addition salts may also be formed and be pharmaceutically acceptable. For a more complete discussion of the preparation and selection of salts, refer to Pharmaceutical Salts: Properties, Selection, and Use (Stahl, P. Heinrich. Wiley-VCHA, Zurich, Switzerland, 2002). It is understood that each of the compounds disclosed herein, and each embodiment of the compounds set forth herein, include pharmaceutically acceptable salts of such compounds. [0051] The compounds of the invention include pharmaceutically acceptable salts thereof. In addition, the compounds of the invention also include other salts of such compounds which are not necessarily pharmaceutically acceptable salts, and which may be useful as intermediates for preparing and/or purifying compounds of the invention and/or for separating enantiomers of compounds of the invention. [0052] It will further be appreciated that the compounds of the invention or their salts may be isolated in the form of solvates, and accordingly that any such solvate is included within the scope of the present invention. For example, compounds of the invention and salts thereof can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. [0053] In some embodiments, the compounds of the invention include the compounds of Examples 1-77 and stereoisomers and pharmaceutically acceptable salts and solvates thereof. In some embodiments, the compounds of Examples 1-77 are in the free base form. In some embodiments, the compounds of Examples 1-77 are in the form of a pharmaceutically acceptable salt. [0054] The term “pharmaceutically acceptable salt,” as used herein, represents salts or zwitterionic forms of the compounds disclosed herein which are water or oil-soluble or dispersible and pharmaceutically acceptable as defined herein. The salts can be prepared during the final isolation and purification of the compounds or separately by reacting the appropriate compound in the form of the free base with a suitable acid. Representative acid addition salts include acetate, adipate, alginate, L-ascorbate, aspartate, benzoate, benzenesulfonate (besylate), bisulfate, butyrate, camphorate, camphorsulfonate, citrate, digluconate, formate, fumarate, gentisate, glutarate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hippurate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethansulfonate (isethionate), lactate, maleate, malonate, DL-mandelate, mesitylenesulfonate, methanesulfonate, naphthylenesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylproprionate, phosphonate, picrate, pivalate, propionate, pyroglutamate, succinate, sulfonate, tartrate, L-tartrate, trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, para-toluenesulfonate (p-tosylate), and undecanoate. Also, basic groups in the compounds of the various embodiments disclosed herein can be quaternized with methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dimethyl, diethyl, dibutyl, and diamyl sulfates; decyl, lauryl, myristyl, and steryl chlorides, bromides, and iodides; and benzyl and phenethyl bromides. Examples of acids which can be employed to form pharmaceutically acceptable addition salts include inorganic acids such as hydrochloric, hydrobromic, sulfuric, and phosphoric, and organic acids such as oxalic, maleic, succinic, and citric. Salts can also be formed by coordination of the compounds with an alkali metal or alkaline earth ion. Hence, the various embodiments disclosed herein contemplates sodium, potassium, magnesium, and calcium salts of the compounds disclosed herein, and the like. [0055] The term “prodrug” refers to a compound that is made active in vivo through chemical reaction in vivo thereby releasing an active compound. Compounds disclosed herein can be modified to exist as prodrugs, as described in Hydrolysis in Drug and Prodrug Metabolism: Chemistry, Biochemistry, and Enzymology (Testa, Bernard and Mayer, Joachim M. Wiley-VHCA, Zurich, Switzerland 2003). Prodrugs of the compounds described herein are structurally modified forms of the compound that readily undergo chemical changes under physiological conditions to provide the active compound. Additionally, prodrugs can be converted to the active compounds by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to a compound when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent. Prodrugs are often useful because, in some situations, they may be easier to administer than the active compound, or parent drug. They may, for instance, be bioavailable by oral administration whereas the parent drug is not. The prodrug may also have improved solubility in pharmaceutical compositions over the parent drug. A wide variety of prodrug derivatives are known in the art, such as those that rely on hydrolytic cleavage or oxidative activation of the prodrug. An example, without limitation, of a prodrug is a compound which is administered as an ester (the “prodrug”), which is then metabolically hydrolyzed to the carboxylic acid, as the active entity. Additional examples include peptidyl derivatives of a compound. The term “therapeutically acceptable prodrug,” refers to those prodrugs or zwitterions that are suitable for use in contact with the tissues of subjects without undue toxicity, irritation, and allergic response, are commensurate with a reasonable benefit/risk ratio, and are effective for their intended use. C. Treatment-Related Definitions [0056] The ability of test compounds to act as inhibitors of EGFR may be demonstrated by the biological assays described herein. Values for inhibiting the activity of EGFR are shown in Tables 20 and 21. [0057] The term “disease” as used herein is intended to be generally synonymous, and is used interchangeably with, the terms “disorder” and “condition” (as in medical condition), in that all reflect an abnormal condition of the body or of one of its parts that impairs normal functioning and is typically manifested by distinguishing signs and symptoms. [0058] The indication “cancer” is to be understood in a most general sense as a disease characterized by inappropriate cellular proliferation, migration, apoptosis, or angiogenesis, preferably by inappropriate cellular proliferation. Inappropriate cell proliferation means cellular proliferation resulting from inappropriate cell growth, from excessive cell division, from cell division at an accelerated rate and/or from inappropriate cell survival. As used herein, the term “cancer” refers to all types of cancer, neoplasm or malignant tumors found in mammals (e.g., but not limited to, humans), including leukemia, lymphomas, carcinomas and sarcomas. [0059] The phrase “effective amount” means an amount of compound that, when administered to a subject in need of such treatment, is sufficient to (i) treat an EGFR pathway-associated disease or disorder, such as an EGFR-associated cancer, (ii) attenuate, ameliorate, or eliminate one or more symptoms of the particular disease, condition, or disorder, or (iii) delay the onset of one or more symptoms of the particular disease, condition, or disorder described herein. The amount of a compound of the invention, or a pharmaceutically acceptable salt thereof that will correspond to such an amount will vary depending upon factors such as the particular compound, disease condition and its severity, the identity (e.g., weight) of the subject in need of treatment, but can nevertheless be routinely determined by one skilled in the art. [0060] Activation of the EGFR pathway is associated with the regulation of several cellular responses, including cell proliferation, inflammatory processes, and extracellular matrix regulation (Rayego-Mateos et al., Mediators Inflamm.2018: 8739473 (2018)). Thus, the phrase “an EGFR pathway-associated disease or disorder” includes proliferative diseases (e.g., cancer or benign neoplasm), inflammatory diseases (e.g., fibrosis), and/or neurodegenerative diseases (e.g. Alzheimer disease). [0061] The term “inflammatory disease” refers to a disease caused by, resulting from, or resulting in inflammation. The term “inflammatory disease” may also refer to a dysregulated inflammatory reaction that causes an exaggerated response by macrophages, granulocytes, and/or T-lymphocytes leading to abnormal tissue damage and/or cell death. An inflammatory disease can be either an acute or chronic inflammatory condition and can result from infections or non-infectious causes. Inflammatory diseases include, without limitation, atherosclerosis, arteriosclerosis, autoimmune disorders, multiple sclerosis, systemic lupus erythematosus, polymyalgia rheumatica (PMR), gouty arthritis, degenerative arthritis, tendonitis, bursitis, psoriasis, cystic fibrosis, arthrosteitis, rheumatoid arthritis, inflammatory arthritis, Sjogren’s syndrome, giant cell arteritis, progressive systemic sclerosis (scleroderma), ankylosing spondylitis, polymyositis, dermatomyositis, pemphigus, pemphigoid, diabetes (e.g., Type I), myasthenia gravis, Hashimoto’s thyroiditis, Graves’ disease, Goodpasture’s disease, mixed connective tissue disease, sclerosing cholangitis, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, pernicious anemia, inflammatory dermatoses, usual interstitial pneumonitis (UIP), asbestosis, silicosis, bronchiectasis, berylliosis, talcosis, pneumoconiosis, sarcoidosis, desquamative interstitial pneumonia, lymphoid interstitial pneumonia, giant cell interstitial pneumonia, cellular interstitial pneumonia, extrinsic allergic alveolitis, Wegener’s granulomatosis and related forms of angiitis (temporal arteritis and polyarteritis nodosa), inflammatory dermatoses, hepatitis, delayed-type hypersensitivity reactions (e.g., poison ivy dermatitis), pneumonia, respiratory tract inflammation, Adult Respiratory Distress Syndrome (ARDS), encephalitis, immediate hypersensitivity reactions, asthma, hayfever, allergies, acute anaphylaxis, rheumatic fever, glomerulonephritis, pyelonephritis, cellulitis, cystitis, chronic cholecystitis, ischemia (ischemic injury), reperfusion injury, allograft rejection, host-versus-graft rejection, appendicitis, arteritis, blepharitis, bronchiolitis, bronchitis, cervicitis, cholangitis, chorioamnionitis, conjunctivitis, dacryoadenitis, dermatomyositis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, gingivitis, ileitis, iritis, laryngitis, myelitis, myocarditis, nephritis, omphalitis, oophoritis, orchitis, osteitis, otitis, pancreatitis, parotitis, pericarditis, pharyngitis, pleuritis, phlebitis, pneumonitis, proctitis, prostatitis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, testitis, tonsillitis, urethritis, urocystitis, uveitis, vaginitis, vasculitis, vulvitis, vulvovaginitis, angitis, chronic bronchitis, osteomyelitis, optic neuritis, temporal arteritis, transverse myelitis, necrotizing fasciitis, and necrotizing enterocolitis. An ocular inflammatory disease includes, but is not limited to, post-surgical inflammation. In certain embodiments, the inflammatory disorder is fibrosis, and the fibrosis is idiopathic pulmonary fibrosis, liver cirrhosis, cystic fibrosis, systemic sclerosis, progressive kidney disease, or cardiovascular fibrosis. [0062] A “therapeutically effective amount” of a compound described herein is an amount sufficient to provide a therapeutic benefit in the treatment of a condition or to delay or minimize one or more symptoms associated with the condition. A therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the treatment of the condition. The term “therapeutically effective amount” can encompass an amount that improves overall therapy, reduces or avoids symptoms, signs, or causes of the condition, and/or enhances the therapeutic efficacy of another therapeutic agent. In certain embodiments, a therapeutically effective amount is an amount sufficient for inhibition of an EGFR protein or gene. In certain embodiments, a therapeutically effective amount is an amount sufficient for treating a proliferative disease. [0063] The expression “patient” and/or “subject” relates to a human or non-human mammalian patient (e.g., mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, and/or primates) suffering from cancer and thus in need of such treatment, preferably the patient is a human person. Furthermore, the expression “patient” and/or “subject” should be understood to include such cancer patients carrying tumors with wild-type EGF receptor as well as pre-selected cancer patients with tumors harboring activating EGFR mutations. These can be located in the tyrosine kinase domain of the EGF receptor such as for instance the L858R or L861 point mutations in the activation loop (exon 21), or in-frame deletion/insertion mutations in the ELREA sequence (exon 19), or substitutions in G719 situated in the nucleotide binding loop (exon 18). Additional activating mutations have been reported in the extracellular domain of the EGF receptor in various indications (e.g. EGFR vIII displaying exon 2-7 deletions). Other mutations such as the T790M point mutation in exon 20 as well as certain exon 20 insertions (e.g. D770_N771insNPG) which confer resistance to particular drugs should also be included, as well as double mutants such as the combined L858R/T790M mutation or the exon-19-del/T790M. In some embodiments, the subject has experienced and/or exhibited at least one symptom of the disease or disorder to be treated and/or prevented. [0064] As used herein, terms “treat” or “treatment” refer to therapeutic or palliative measures. Beneficial or desired clinical results include, but are not limited to, alleviation, in whole or in part, of symptoms associated with a disease or disorder or condition, diminishment of the extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state (e.g., one or more symptoms of the disease), and remission (whether partial or total), whether detectable or undetectable. “Treatment” can also mean prolonging survival as compared to expected survival if not receiving treatment. [0065] As used herein the term “inhibit” or “inhibition” in the context of proteins, for example, in the context of EGFR tyrosine kinase, refers to a reduction in the activity of the tyrosine kinase. In some embodiments, the term refers to a reduction of the level of activity of EGFR to a level that is statistically significantly lower than an initial level, which may, for example, be a baseline level of activity. In some embodiments, the term refers to a reduction of the level of EGFR activity to a level that is less than 75%, less than 50%, less than 40%, less than 30%, less than 25%, less than 20%, less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, less than 0.1%, less than 0.01%, less than 0.001%, or less than 0.0001% of an initial level, which may, for example, be a baseline level of tyrosine kinase activity. [0066] A “proliferative disease” refers to a disease that occurs due to abnormal growth or extension by the proliferation of cells. A proliferative disease may be associated with: 1) the pathological proliferation of normally quiescent cells; 2) the pathological migration of cells from their normal location (e.g., metastasis of neoplastic cells); 3) the pathological expression of proteolytic enzymes such as the matrix metalloproteinases (e.g., collagenases, gelatinases, and elastases); or 4) the pathological angiogenesis as in proliferative retinopathy and tumor metastasis. Exemplary proliferative diseases include cancers (i.e., “malignant neoplasms”), benign neoplasms, angiogenesis, inflammatory diseases, and autoimmune diseases.

III. COMPOUND EMBODIMENTS A. Compounds of Formula (I) [0067] In some embodiments, there are provided compounds of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein: Ring A is a C₆-C₁₀ aryl or 5- to 10-membered heteroaryl; X is CH or N; R¹ is hydrogen or C₁-C₃ alkyl; R², R³, R⁴ and R⁵ are independently selected at each occurrence from the group consisting of hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, and –(C₁-C₃ alkylene)-O-R¹¹, wherein R² and R³ or R⁴ and R⁵ may optionally be taken together with the atom to which they are attached to form a 3- to 6-membered cycloalkyl or a 4- to 7-membered heterocyclyl, or R² or R³ and R⁴ or R⁵ may optionally be taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring; R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, phenyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –(CH₂)_mO(CH₂)_m-(C₁-C₃ alkoxy), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(aryl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(heteroaryl), –NH-aryl, –C(O)-(4- to 7-membered heterocyclyl), heteroaryl, 4- to 10-membered heterocyclyl, 3- to 6-membered cycloalkyl, –CH₂S(O)₂CH₃, –CH₂S(O)NCH₃ and cyano; R⁷ is selected from hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, –C₁-C₄ alkylene-(C₁-C₃ alkoxy), 3- to 6-membered cycloalkyl, –O-(3- to 6-membered cycloalkyl), –O-heteroaryl, –O-(C₁-C₄ alkylene)-(C₁-C₃ alkoxy), –O-(C₁-C₃ alkoxy)-heteroaryl, –O-(C₁-C₄ alkylene)-(4- to 7-membered heterocyclyl), –O-(C₁-C₄ alkylene)-O-(3- to 6-membered cycloalkyl), –NH-CH₂-heteroaryl, –O-CH₂-heteroaryl and ; R⁸ is hydrogen, C₁-C₃ alkyl, or C₁-C₆ haloalkyl; or R⁷ and R⁸ are taken together to form a fused bicyclic heteroaromatic ring; R⁹ is independently selected at each occurrence thereof from the group consisting of halogen, cyano, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, and -O-(C₁-C₃ haloalkyl); R¹⁰ is selected from heterocyclyl, cycloalkyl, and heteroaryl; R¹¹ is C₁-C₃ alkyl or heteroaryl; m is 0, 1, 2 or 3; and n is 0, 1, 2, 3, 4 or 5; wherein: each alkyl is optionally substituted with one or more substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₃-C₆ cycloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy and -OCD₃; each cycloalkyl is optionally substituted with one to three substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy and -OCD₃; each heterocyclyl ring is optionally substituted with one to four substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₃-C₆ cycloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy, OCD₃, -S(O)₂CH₃, -C(O)-C₁-C₃ alkyl, and 5-membered heteroaryl optionally substituted with one C₁-C₃ alkyl; each aryl is optionally substituted with one to three substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl and C₁-C₃ alkoxy; and each heteroaryl, or bicyclic heteroaryl is optionally substituted with one to three substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, , an optionally substituted -O-(C₃-C₆ cycloalkyl) and an optionally substituted -O-(4- to 6-membered heterocyclyl). [0068] For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75^th Ed. Additionally, general principles of organic chemistry are described in “Organic Chemistry,” Thomas Sorrell, University Science Books, Sausalito: 1999, and “March’s Advanced Organic Chemistry,” 5^th Ed., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference. [0069] As described herein, the compounds of the invention comprise multiple variable groups (e.g., Ring A, X, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R^a, R^b, R^c, m, and n). As one of ordinary skill in the art will recognize, combinations of groups envisioned by this invention are those combinations that result in the formation of stable or chemically feasible compounds. The term “stable,” in this context, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and preferably their recovery, purification, and use for one or more of the purposes disclosed herein. In some embodiments, a stable compound or chemically feasible compound is one that is not substantially altered when kept at a temperature of 40 ^C or less, in the absence of moisture or other chemically reactive conditions, for at least a week. [0070] Unless otherwise specified, the compounds of the invention, whether identified by chemical name or chemical structure, include all stereoisomers (e.g., enantiomers and diastereomers), double bond isomers (e.g., (Z) and (E)), conformational isomers including atropisomers, and tautomers of the compounds identified by the chemical names and chemical structures provided herein. In addition, single stereoisomers, double bond isomers, conformational isomers including atropisomers, and tautomers as well as mixtures of stereoisomers, double bond isomers, conformational isomers including atropisomers, and tautomers are within the scope of the invention. [0071] Atropisomers are defined as a subclass of conformers which can be isolated as separate chemical species and which arise from restricted rotation about a single bond. The absolute configuration of atropisomers are designated R_a or S_a based on the Cahn-Ingold-Prelog priority rules, wherein the group on the “front” of the atropisomer is assigned the highest priority. Where an atropisomer disclosed herein is described with the stereochemical descriptor “R_a” and “S_a”, the recited chemical name was prepared using ChemDraw Professional (Version 22.0.0.22), unless noted otherwise. [0072] Enantiomers are defined as one of a pair of molecular entities which are mirror images of each other and non-superimposable. The absolute configuration of enantiomers are designated R or S based on the Cahn-Ingold-Prelog priority rules. [0073] Diastereomers or diastereoisomers are defined as stereoisomers other than enantiomers. Diastereomers or diastereoisomers are stereoisomers not related as mirror images. Diastereomers or diastereoisomers are characterized by differences in physical properties, and by some differences in chemical behavior towards achiral as well as chiral reagents. [0074] Tautomers are defined as two or more compounds that differ by the position of a single hydrogen atom. Typically, compounds that demonstrate tautomerism readily interconvert between the two or more tautomeric forms. Examples of tautomerism include, but are not limited to, the keto and enol forms of ketone-containing compounds, the amide and imidic acid forms of compounds containing an amide bond, as well as the hydroxypyridine and pyridone forms of compounds containing a hydroxy-substituted pyridine ring. [0075] As used herein, in any chemical structure or formula, a non-bold, straight bond attached to a stereocenter of a compound, such as in

denotes that the configuration of the stereocenter is unspecified. The compound may have any configuration, or a mixture of configurations, at the stereocenter. [0076] Certain compounds of the invention are atropisomers wherein the orientation of the rotational bond is depicted by the group in front in bold and the group in the back is faded, as shown below.

(R_a)-8-((2,3-difluorophenyl)amino)-6-(methoxymethyl)- (S_a)-8-((2,3-difluorophenyl)amino)-6-(methoxymethyl)- 4,4-dimethyl-7-(thieno[3,2-d]pyrimidin-4-yl)-3,4- 4,4-dimethyl-7-(thieno[3,2-d]pyrimidin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one dihydropyrrolo[1,2-a]pyrazin-1(2H)-one Alternatively, the orientation of the rotational bond of an atropisomer may be depicted by drawing the group in front in bold without the group in the back being shown as faded, as shown below.

(R_a)-8-((2,3-difluorophenyl)amino)-6-(methoxymethyl)- (S_a)-8-((2,3-difluorophenyl)amino)-6-(methoxymethyl)- 4,4-dimethyl-7-(thieno[3,2-d]pyrimidin-4-yl)-3,4- 4,4-dimethyl-7-(thieno[3,2-d]pyrimidin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one dihydropyrrolo[1,2-a]pyrazin-1(2H)-one [0077] In the specification and claims, unless otherwise specified, any atom not specifically designated as a particular isotope in any compound of the invention is meant to represent any stable isotope of the specified element. In the Examples, where an atom is not specifically designated as a particular isotope in any compound of the invention, no effort was made to enrich that atom in a particular isotope, and therefore a person of ordinary skill in the art would understand that such atom likely was present at approximately the natural abundance isotopic composition of the specified element. [0078] As used herein, the term “stable,” when referring to an isotope, means that the isotope is not known to undergo spontaneous radioactive decay. Stable isotopes include, but are not limited to, the isotopes for which no decay mode is identified in V.S. Shirley & C.M. Lederer, Isotopes Project, Nuclear Science Division, Lawrence Berkeley Laboratory, Table of Nuclides (January 1980). [0079] As used herein in the specification and claims, “H” refers to hydrogen and includes any stable isotope of hydrogen, namely ¹H and D. In the Examples, where an atom is designated as “H,” no effort was made to enrich that atom in a particular isotope of hydrogen, and therefore a person of ordinary skill in the art would understand that such hydrogen atom likely was present at approximately the natural abundance isotopic composition of hydrogen. [0080] As used herein, “¹H” refers to protium. Where an atom in a compound of the invention, or a pharmaceutically acceptable salt thereof, is designated as protium, protium is present at the specified position with at least the natural abundance concentration of protium. [0081] As used herein, “D,” “d,” and “²H” refer to deuterium. [0082] In some embodiments, the compounds of the invention and pharmaceutically acceptable salts thereof, include each constituent atom at approximately the natural abundance isotopic composition of the specified element. [0083] In some embodiments, the compounds of the invention and pharmaceutically acceptable salts thereof, include one or more atoms having an atomic mass or mass number that differs from the atomic mass or mass number of the most abundant isotope of the specified element (“isotope-labeled” compounds and salts). Examples of stable isotopes which are commercially available and suitable for the invention include without limitation isotopes of hydrogen, carbon, nitrogen, oxygen, and phosphorus, for example ²H, ¹³C, ¹⁵N, ¹⁸O, ¹⁷O, and ³¹P, respectively. [0084] The isotope-labeled compounds and salts can be used in a number of beneficial ways, including as medicaments. In some embodiments, the isotope-labeled compounds and salts are deuterium (²H)-labeled. Deuterium (²H)-labeled compounds and salts are therapeutically useful with potential therapeutic advantages over the non-²H-labeled compounds. In general, deuterium (²H)-labeled compounds and salts can have higher metabolic stability as compared to those that are not isotope-labeled owing to the kinetic isotope effect described below. Higher metabolic stability translates directly into an increased in vivo half-life or lower dosages, which under most circumstances would represent a preferred embodiment of the present invention. The isotope-labeled compounds and salts can usually be prepared by carrying out the procedures disclosed in the synthesis schemes, the Examples, and the related description, replacing a non-isotope-labeled reactant by a readily available isotope-labeled reactant. [0085] The deuterium (²H)-labeled compounds and salts can manipulate the rate of oxidative metabolism of the compound by way of the primary kinetic isotope effect. The primary kinetic isotope effect is a change of the rate for a chemical reaction that results from exchange of isotopic nuclei, which in turn is caused by the change in ground state energies of the covalent bonds involved in the reaction. Exchange of a heavier isotope usually results in a lowering of the ground state energy for a chemical bond and thus causes a reduction in the rate-limiting bond breakage. If the bond breakage occurs in or in the vicinity of a saddle-point region along the coordinate of a multi-product reaction, the product distribution ratios can be altered substantially. For example, if deuterium is bonded to a carbon atom at a non- exchangeable position, rate differences of k_H/k_D = 2-7 are typical. For a further discussion, see S. L. Harbeson and R. D. Tung, Deuterium In Drug Discovery and Development, Ann. Rep. Med. Chem.2011, 46, 403-417, incorporated in its entirety herein by reference. [0086] The concentration of an isotope (e.g., deuterium) incorporated at a given position of an isotope-labeled compound of the invention, or a pharmaceutically acceptable salt thereof, may be defined by the isotopic enrichment factor. The term “isotopic enrichment factor,” as used herein, means the ratio between the abundance of an isotope at a given position in an isotope-labeled compound (or salt) and the natural abundance of the isotope. [0087] Where an atom in a compound of the invention, or a pharmaceutically acceptable salt thereof, is designated as deuterium, such compound (or salt) has an isotopic enrichment factor for such atom of at least 3000 (~45% deuterium incorporation). In some embodiments, the isotopic enrichment factor is at least 3500 (~52.5% deuterium incorporation), at least 4000 (~60% deuterium incorporation), at least 4500 (~67.5% deuterium incorporation), at least 5000 (~75% deuterium incorporation), at least 5500 (~82.5% deuterium incorporation), at least 6000 (~90% deuterium incorporation), at least 6333.3 (~95% deuterium incorporation), at least 6466.7 (~97% deuterium incorporation), at least 6600 (~99% deuterium incorporation), or at least 6633.3 (~99.5% deuterium incorporation). [0088] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R², R³, R⁴ and R⁵ are independently selected at each occurrence from the group consisting of hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, and –(C₁-C₃ alkylene)-O-R¹¹, wherein R² and R³ or R⁴ and R⁵ may optionally be taken together with the atom to which they are attached to form a 3- to 6-membered cycloalkyl, or R² or R³ and R⁴ or R⁵ may optionally be taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. [0089] In some embodiments, the invention relates to a compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein: Ring A is C₆-C₁₀ aryl or 5- to 10-membered heteroaryl; X is CH or N; R¹ is hydrogen or C₁-C₃ alkyl; R² is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; R³ is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; or R² and R³, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a; R⁴ is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; R⁵ is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; or R⁴ and R⁵, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a; or one of R² and R³ and one of R⁴ and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclic ring, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a; R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, phenyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –(CH₂)_mO(CH₂)_m-(C₁-C₃ alkoxy), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(C₆-C₁₀ aryl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl), –NH-(C₆-C₁₀ aryl), –C(O)-(4- to 7-membered heterocyclyl), 5- to 10-membered heteroaryl, 4- to 10-membered heterocyclyl, C₃-C₆ cycloalkyl, –CH₂S(O)₂CH₃, –CH₂S(O)NCH₃, cyano, and C₁-C₃ cyanoalkyl, wherein said 4- to 10-membered heterocyclyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), or –C(O)-(4- to 7-membered heterocyclyl) is optionally substituted with 1-4 R^a, and said 5- to 10-membered heteroaryl or –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) is optionally substituted with 1-3 R^b; R⁷ is selected from hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, –C₁-C₄ alkylene-(C₁-C₃ alkoxy), C₃-C₆ cycloalkyl, –O-(C₃-C₆ cycloalkyl), –O-(5- to 10-membered heteroaryl), –O-(C₁-C₄ alkylene)-(C₁-C₃ alkoxy), –O-(C₁-C₃ alkoxy)-(5- to 10-membered heteroaryl), –O-(C₁-C₄ alkylene)-(4- to 7-membered heterocyclyl), –O-(C₁-C₄ alkylene)-O-(C₃-C₆ cycloalkyl), –NH-CH₂-(5- to 10-membered heteroaryl), –O-CH₂-(5- to 10-membered heteroaryl), and , wherein said –O-(C₁-C₄ alkylene)-(4- to 7-membered heterocyclyl) is optionally substituted with 1-4 R^a, and said –O-(5- to 10-membered heteroaryl), –O-(C₁-C₃ alkoxy)-(5- to 10-membered heteroaryl), or –NH-CH₂-(5- to 10-membered heteroaryl) is optionally substituted with 1-3 R^b; R⁸ is hydrogen, C₁-C₃ alkyl, or C₁-C₆ haloalkyl; or R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1-3 R^c; each R⁹ is independently selected from the group consisting of halogen, cyano, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, and –O-(C₁-C₃ haloalkyl); R¹⁰ is selected from 4- to 7-membered heterocyclyl optionally substituted with 1-3 R^a, C₃-C₆ cycloalkyl, and 5- to 10-membered heteroaryl optionally substituted with 1-3 R^b; each R¹¹ is independently C₁-C₃ alkyl or 5- to 10-membered heteroaryl, wherein said 5- to 10-membered heteroaryl is optionally substituted with 1-3 R^b; each R^a is independently selected from halogen, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₃-C₆ cycloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy, –OCD₃, –S(O)₂CH₃, –C(O)-C₁-C₃ alkyl, and 5-membered heteroaryl optionally substituted with one C₁-C₃ alkyl; each R^b is independently selected from halogen, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, –O-(C₃-C₆ cycloalkyl), and –O-(4- to 6-membered heterocyclyl) optionally substituted with 1-4 R^a; each R^c is independently selected from halogen, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, –O-(C₃-C₆ cycloalkyl), and –O-(4- to 6-membered heterocyclyl) optionally substituted with 1-4 R^a; each m is independently 0, 1, 2, or 3; and n is 0, 1, 2, 3, 4, or 5. [0090] In some embodiments, the invention relates to a compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein: Ring A is C₆-C₁₀ aryl or 5- to 10-membered heteroaryl; X is CH or N; R¹ is hydrogen or C₁-C₃ alkyl; R² is hydrogen or C₁-C₆ alkyl; R³ is hydrogen or C₁-C₆ alkyl; or R² and R³, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl; R⁴ is hydrogen or C₁-C₆ alkyl; R⁵ is hydrogen or C₁-C₆ alkyl; or one of R² and R³ and one of R⁴ and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl; R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl), 5- to 10-membered heteroaryl, 4- to 10-membered heterocyclyl, cyano, and C₁-C₃ cyanoalkyl, wherein said 4- to 10-membered heterocyclyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), or –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) is optionally substituted with 1-2 R^a, and said 5- to 10-membered heteroaryl or –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) is optionally substituted with 1 R^b; R⁷ is selected from hydrogen, halogen, and ; R⁸ is hydrogen; or R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1 R^c; each R⁹ is independently selected from the group consisting of halogen, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, and –O-(C₁-C₃ haloalkyl); R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 R^b; each R^a is independently selected from halogen, oxo, C₁-C₃ alkyl, and C₁-C₃ alkoxy; each R^b is independently selected from C₁-C₃ alkyl; R^c is C₁-C₃ alkoxy; each m is independently 0, 1, or 2; and n is 0, 1, or 2. [0091] In some embodiments, X is CH. In other embodiments, X is N. [0092] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is CH. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is N. [0093] In some embodiments, Ring A is C₆-C₁₀ aryl. In some embodiments, Ring A is a phenyl ring. In some embodiments, Ring A is a naphthyl ring. In other embodiments, Ring A is a 5- to 10-membered heteroaryl. In some embodiments, Ring A is a 5-membered heteroaryl. In some embodiments, Ring A is a 6-membered heteroaryl. In some embodiments, Ring A is a 7-membered heteroaryl. In some embodiments, Ring A is an 8-membered heteroaryl. In some embodiments, Ring A is a 9-membered heteroaryl. In some embodiments, Ring A is a 10-membered heteroaryl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

[0094] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is C₆-C₁₀ aryl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl. [0095] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is a 5- to 10-membered heteroaryl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is a 9-membered heteroaryl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is a 10-membered heteroaryl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from phenyl, benzo[d]isothiazol-3-yl, benzo[d]thiazol-4-yl, and quinolin-8-yl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is benzo[d]isothiazol-3-yl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is benzo[d]thiazol-4-yl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is quinolin-8-yl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl,

. In other embodiments, Ring A is

. In other embodiments, Ring A is

. In other embodiments, Ring A is

. [0096] In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. [0097] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein n is 0. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein n is 1. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein n is 2. [0098] In some embodiments, R⁹ is independently selected at each occurrence thereof from the group consisting of halogen, cyano, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, and -O-(C₁-C₃ haloalkyl). [0099] In some embodiments, one or more R⁹ is halogen. In some the halogen is chloro, bromo, fluoro, or iodo. [0100] In some embodiments, one or more R⁹ is C₁-C₃ alkyl. In some embodiments, the alkyl is an unsubstituted C₁-C₃ alkyl. In some embodiments, the alkyl is methyl, ethyl, n-propyl, or isopropyl. In some embodiments, the alkyl is a substituted C₁-C₃ alkyl. [0101] In some embodiments, one or more R⁹ is C₁-C₃ alkoxy. In some embodiments, the alkoxy is an unsubstituted C₁ alkoxy. In some embodiments, the alkoxy is a substituted C₁ alkoxy. In some embodiments, the alkoxy is an unsubstituted C₂ alkoxy. In some embodiments, the alkoxy is a substituted C₂ alkoxy. In some embodiments, the alkoxy is an unsubstituted C₃ alkoxy. In some embodiments, the alkoxy is a substituted C₃ alkoxy. [0102] In some embodiments, one or more of R⁹ is C₁-C₃ haloalkyl. In some embodiments, the haloalkyl is chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloroethyl e.g., 1-chloroethyl and 2-chloroethyl, trichloroethyl e.g., 1,2,2-trichloroethyl, 2,2,2-trichloroethyl, fluoroethyl e.g. 1-fluoromethyl and 2-fluoroethyl, difluoroethyl e.g.1,1-difluoroethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl e.g.1,2,2-trifluoroethyl and 2,2,2-trifluoroethyl, chloropropyl, trichloropropyl, fluoropropyl, or trifluoropropyl. [0103] In some embodiments, one or more R⁹ is -O-(C₁-C₃ haloalkyl). In some embodiments, the C₁-C₃ haloalkyl is chloromethyl, fluoromethyl, diflouoromethyl, trifluoromethyl, chloroethyl e.g., 1-chloroethyl and 2-chloroethyl, trichloroethyl e.g., 1,2,2-trichloroethyl, 2,2,2-trichloroethyl, fluoroethyl e.g.1-fluoromethyl and 2-fluoroethyl, difluoroethyl e.g.1,1-difluoroethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl e.g.1,2,2-trifluoroethyl and 2,2,2-trifluoroethyl, chloropropyl, trichloropropyl, fluoropropyl, or trifluoropropyl. [0104] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein each R⁹ is independently selected from the group consisting of halogen, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, and –O-(C₁-C₃ haloalkyl). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least one R⁹ is halogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least one R⁹ is C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least one R⁹ is C₁-C₃ alkoxy. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least one R⁹ is C₁-C₃ haloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least one R⁹ is –O-(C₁-C₃ haloalkyl). In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein each R⁹ is independently selected from the group consisting of Cl, F, –CH₃, –CH₂CH₃, –OCH₃, –CF₃, and –OCHF₂. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is Cl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is F. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –CH₂CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –OCH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –CF₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –OCHF₂. [0105] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl and n is 0. [0106] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl and n is 1. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 1, and R⁹ is selected from halogen, C₁-C₃ alkoxy, and C₁-C₃ haloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 1, and R⁹ is halogen. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 1, and R⁹ is C₁-C₃ alkoxy. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 1, and R⁹ is and C₁-C₃ haloalkyl. [0107] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 1, and R⁹ is selected from F, Cl, –OCH₃, and –CF₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 1, and R⁹ is F. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 1, and R⁹ is Cl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 1, and R⁹ is –OCH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 1, and R⁹ is –CF₃. [0108] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and each R⁹ is independently selected from halogen, C₁-C₃ alkyl, C₁-C₃ alkoxy, and –O-(C₁-C₃ haloalkyl). In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and each R⁹ is halogen. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, a first R⁹ is halogen, and a second R⁹ is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, a first R⁹ is halogen, and a second R⁹ is C₁-C₃ alkoxy. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, a first R⁹ is halogen, and a second R⁹ is –O-(C₁-C₃ haloalkyl). In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and each R⁹ is independently selected from F, Cl, –CH₃, –CH₂CH₃, –OCH₃, and –OCHF₂. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and each R⁹ is F. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, a first R⁹ is F, and a second R⁹ is Cl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and each R⁹ is Cl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and a first R⁹ is F, and a second R⁹ is –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and a first R⁹ is Cl, and a second R⁹ is –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and a first R⁹ is F, and a second R⁹ is –CH₂CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and a first R⁹ is F, and a second R⁹ is –OCH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and a first R⁹ is Cl, and a second R⁹ is –OCH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and a first R⁹ is F, and a second R⁹ is –OCHF₂. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl, n is 2, and at least one R⁹ is halogen. [0109] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from

, ,

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring

_{other embodiments, the} invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is

_{. In other embodiments, the} invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring

. [0110] In some embodiments, R¹ is hydrogen. Alternatively, in some embodiments, R¹ is an unsubstituted C₁-C₃ alkyl. In some embodiments, R¹ is a methyl, ethyl, or propyl. In some embodiments, R¹ is methyl. Alternatively, in some embodiments, R¹ is a substituted C₁-C₃ alkyl. In some embodiments, R¹ is a substituted methyl, ethyl, or propyl. In some embodiments, R¹ is a hydrogen or methyl. [0111] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen. [0112] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is an unsubstituted C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen or –CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is –CH₃. [0113] In some embodiments, R², R³, R⁴ and R⁵ are independently selected at each occurrence from the group consisting of hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, and –(C₁-C₃ alkylene)-O-R¹¹. In some embodiments, R², R³, R⁴, and R⁵ are hydrogen. In some embodiments, one or more of R², R³, R⁴, and R⁵ is halogen. In some embodiments, one or more of R², R³, R⁴, and R⁵ is chloro, bromo, fluoro, or iodo. [0114] In some embodiments, one or more of R², R³, R⁴, and R⁵ is C₁-C₆ alkyl. In some embodiments one or more of R², R³, R⁴, and R⁵ is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tetrabutyl, pentyl, or hexyl. In some embodiments, R² is C₁-C₆ alkyl. In some embodiments, R³ is C₁-C₆ alkyl. In some embodiments, R⁴ is C₁-C₆ alkyl. In some embodiments, R⁵ is C₁-C₆ alkyl. In some embodiments, the C₁-C₆ alkyl of the one or more of R², R³, R⁴, and R⁵ is an unsubstituted C₁-C₆ alkyl. In some embodiments, the C₁-C₆ alkyl of the one or more of R², R³, R⁴, and R⁵ is a substituted C₁-C₆ alkyl. [0115] In some embodiments, one or more of R², R³, R⁴, and R⁵ is methyl. In some embodiments, R⁴ and R⁵ are methyl. In some embodiments, R⁵ is methyl. [0116] In some embodiments, one or more of R², R³, R⁴, and R⁵ is C₁-C₆ alkoxy. In some embodiments, one or more of R², R³, R⁴, and R⁵ is an unsubstituted C₁ alkoxy. In some embodiments, one or more of R², R³, R⁴, and R⁵ is a substituted C₁ alkoxy. In some embodiments, one or more of R², R³, R⁴, and R⁵ is an unsubstituted C₂ alkoxy. In some embodiments, one or more of R², R³, R⁴ , and R⁵ is a substituted C₂ alkoxy. In some embodiments, one or more of R², R³, R⁴, and R⁵ is an unsubstituted C₃ alkoxy. In some embodiments, one or more of R², R³, R⁴, and R⁵ is a substituted C₃ alkoxy. In some embodiments, one or more of R², R³, R⁴, and R⁵ is an unsubstituted C₄ alkoxy. In some embodiments, one or more of R², R³, R⁴, and R⁵ is a substituted C₄ alkoxy. In some embodiments, one or more of R², R³, R⁴, and R⁵ is an unsubstituted C₅ alkoxy. In some embodiments, one or more of R², R³, R⁴, and R⁵ is a substituted C₅ alkoxy. In some embodiments, one or more of R², R³, R⁴, and R⁵ is an unsubstituted C₆ alkoxy. In some embodiments, one or more of R², R³, R⁴, and R⁵ is a substituted C₆ alkoxy. [0117] In some embodiments, one or more of R², R³, R⁴ and R⁵ is –(C₁-C₃ alkylene)-O-R¹¹. In some embodiments, the C₁-₃ alkylene is methylene, ethylene, or dimethyl-methylene. In some embodiments, R¹¹ is C₁-C₃ alkyl. In some embodiments, R¹¹ is methyl, ethyl, n-propyl, or isopropyl. In some embodiments, R¹¹ is heteroaryl. In some embodiments, R¹¹ is an unsubstituted heteroaryl. In some embodiments, R¹¹ is a substituted heteroaryl. In some embodiments, R¹¹ is methyl or heteroaryl. [0118] In some embodiments, R⁵ is hydrogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹. In some embodiments, R⁵ is hydrogen, methyl, –CH₂-O-CH₃, –C(CH₃)₂-O-

. [0119] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R², R³, R⁴ , and R⁵ are independently selected at each occurrence from hydrogen and C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least one of R², R³, R⁴, and R⁵ is hydrogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least one of R², R³, R⁴, and R⁵ is C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³ are each C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ and R⁵ are each C₁-C₆ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R², R³, R⁴, and R⁵ are independently selected at each occurrence from hydrogen and –CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least one of R², R³, R⁴, and R⁵ is –CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³ are each –CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ and R⁵ are each –CH₃. [0120] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is hydrogen or C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is hydrogen or C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is hydrogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is unsubstituted C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is unsubstituted C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is hydrogen or –CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is –CH₃. [0121] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is hydrogen or C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is hydrogen or C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is hydrogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is unsubstituted C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is unsubstituted C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is hydrogen or –CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is –CH₃. [0122] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is hydrogen or C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is hydrogen or C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is hydrogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is unsubstituted C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is unsubstituted C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is hydrogen or –CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is –CH₃. [0123] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is hydrogen or C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is hydrogen or C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is hydrogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is unsubstituted C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is unsubstituted C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is hydrogen or –CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is –CH₃. [0124] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R², R³, R⁴, and R⁵ are each hydrogen. [0125] In some embodiments, R² and R³ are taken together to form a 3- to 6-membered cycloalkyl. In some embodiments, the 3- to 6-membered cycloalkyl is an unsubstituted 3- to 6-membered cycloalkyl. In some embodiments, the 3- to 6-membered cycloalkyl is a substituted 3- to 6-membered cycloalkyl. [0126] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³ are taken together to form a 3- to 6-membered cycloalkyl or a 4- to 7-membered heterocyclyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³ are taken together to form a 3- to 6-membered cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³ are taken together to form a cyclobutyl. In some embodiments, the 3- to 6-membered cycloalkyl is an unsubstituted 3- to 6-membered cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³ are taken together to form an unsubstituted cyclobutyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³ are taken together to form a 4- to 7-membered heterocyclyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³ are taken together to form an oxetanyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³ are taken together to form an unsubstituted 4- to 7-membered heterocyclyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³ are taken together to form an unsubstituted oxetanyl. [0127] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form a cyclobutyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form an unsubstituted C₃-C₆ cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form an unsubstituted cyclobutyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form a 4- to 7-membered heterocyclyl optionally substituted with 1-4 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form an oxetanyl optionally substituted with 1-4 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form an unsubstituted 4- to 7-membered heterocyclyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form an unsubstituted oxetanyl. [0128] In some embodiments, R⁴ and R⁵ are taken together to form a 3- to 6-membered cycloalkyl. In some embodiments, the 3- to 6-membered cycloalkyl is an unsubstituted 3- to 6-membered cycloalkyl. In some embodiments, the 3- to 6-membered cycloalkyl is a substituted 3- to 6-membered cycloalkyl. [0129] In some embodiments, R² or R³ and R⁴ or R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. In some embodiments, R² and R⁴ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. In some embodiments, R² and R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. In some embodiments, R³ and R⁴ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. In some embodiments, R³ and R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. In some embodiments, the 3- to 6-membered cycloalkyl is an unsubstituted 3- to 6-membered cycloalkyl. In some embodiments, the 3- to 6-membered cycloalkyl is a substituted 3- to 6-membered cycloalkyl. In some embodiments, the 3- to 6-membered heterocyclic ring is a substituted heterocyclic ring. In some embodiments, the 3- to 6-membered heterocyclic ring is an unsubstituted heterocyclic ring. [0130] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² or R³ and R⁴ or R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁴ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁴ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. [0131] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² or R³ and R⁴ or R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁴ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁴ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl. [0132] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² or R³ and R⁴ or R⁵ are taken together with the atoms to which they are attached to form a cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁴ are taken together with the atoms to which they are attached to form a cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁵ are taken together with the atoms to which they are attached to form a cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁴ are taken together with the atoms to which they are attached to form a cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁵ are taken together with the atoms to which they are attached to form a cyclopentyl. [0133] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² or R³ and R⁴ or R⁵ are taken together with the atoms to which they are attached to form an unsubstituted 3- to 6-membered cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁴ are taken together with the atoms to which they are attached to form an unsubstituted 3- to 6-membered cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁵ are taken together with the atoms to which they are attached to form an unsubstituted 3- to 6-membered cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁴ are taken together with the atoms to which they are attached to form an unsubstituted 3- to 6-membered cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl. [0134] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² or R³ and R⁴ or R⁵ are taken together with the atoms to which they are attached to form an unsubstituted cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁴ are taken together with the atoms to which they are attached to form an unsubstituted cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁵ are taken together with the atoms to which they are attached to form an unsubstituted cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁴ are taken together with the atoms to which they are attached to form an unsubstituted cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁵ are taken together with the atoms to which they are attached to form an unsubstituted cyclopentyl. [0135] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein one of R² and R³ and one of R⁴ and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclic ring, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁴, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclic ring, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclic ring, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁴, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclic ring, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclic ring, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a. [0136] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein one of R² and R³ and one of R⁴ and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁴, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁴, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl. [0137] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein one of R² and R³ and one of R⁴ and R⁵, together with the carbon atoms to which they are attached, form a cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁴, together with the carbon atoms to which they are attached, form a cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁵, together with the carbon atoms to which they are attached, form a cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁴, together with the carbon atoms to which they are attached, form a cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁵, together with the carbon atoms to which they are attached, form a cyclopentyl. [0138] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein one of R² and R³ and one of R⁴ and R⁵, together with the carbon atoms to which they are attached, form an unsubstituted C₃-C₆ cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁴, together with the carbon atoms to which they are attached, form an unsubstituted C₃-C₆ cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁵, together with the carbon atoms to which they are attached, form an unsubstituted C₃-C₆ cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁴, together with the carbon atoms to which they are attached, form an unsubstituted C₃-C₆ cycloalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁵, together with the carbon atoms to which they are attached, form an unsubstituted C₃-C₆ cycloalkyl. [0139] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein one of R² and R³ and one of R⁴ and R⁵, together with the carbon atoms to which they are attached, form an unsubstituted cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁴, together with the carbon atoms to which they are attached, form an unsubstituted cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² and R⁵, together with the carbon atoms to which they are attached, form an unsubstituted cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁴, together with the carbon atoms to which they are attached, form an unsubstituted cyclopentyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ and R⁵, together with the carbon atoms to which they are attached, form an unsubstituted cyclopentyl. [0140] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹, R², R³, R⁴, and R⁵ are each hydrogen. [0141] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is C₁-C₃ alkyl, and R², R³, R⁴, and R⁵ are each hydrogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is –CH₃, and R², R³, R⁴, and R⁵ are each hydrogen. [0142] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is C₁-C₆ alkyl, R³ is C₁-C₆ alkyl, R⁴ is hydrogen, and R⁵ is hydrogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is C₁-C₃ alkyl, R³ is C₁-C₃ alkyl, R⁴ is hydrogen, and R⁵ is hydrogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is –CH₃, R³ is –CH₃, R⁴ is hydrogen, and R⁵ is hydrogen. [0143] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is hydrogen, R³ is hydrogen, R⁴ is C₁-C₆ alkyl, and R⁵ is C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is hydrogen, R³ is hydrogen, R⁴ is C₁-C₃ alkyl, and R⁵ is C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is hydrogen, R³ is hydrogen, R⁴ is –CH₃, and R⁵ is –CH₃. [0144] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, R² is hydrogen, R³ is hydrogen, R⁴ is C₁-C₆ alkyl, and R⁵ is hydrogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, R² is hydrogen, R³ is hydrogen, R⁴ is C₁-C₃ alkyl, and R⁵ is hydrogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, R² is hydrogen, R³ is hydrogen, R⁴ is –CH₃, and R⁵ is hydrogen. [0145] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, R² is hydrogen, R³ is hydrogen, R⁴ is hydrogen, and R⁵ is C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, R² is hydrogen, R³ is hydrogen, R⁴ is hydrogen, and R⁵ is C₁-C₆ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, R² is hydrogen, R³ is hydrogen, R⁴ is hydrogen, and R⁵ is –CH₃. [0146] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³ are taken together with the atom to which they are attached to form a 3- to 6-membered cycloalkyl or a 4- to 7-membered heterocyclyl. [0147] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³ are taken together with the atom to which they are attached to form a 3- to 6-membered cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³ are taken together with the atom to which they are attached to form a cyclobutyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³ are taken together with the atom to which they are attached to form an unsubstituted 3- to 6-membered cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³ are taken together with the atom to which they are attached to form an unsubstituted cyclobutyl. [0148] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³ are taken together with the atom to which they are attached to form a 4- to 7-membered heterocyclyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³ are taken together with the atom to which they are attached to form an oxetanyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³ are taken together with the atom to which they are attached to form an unsubstituted 4- to 7-membered heterocyclyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³ are taken together with the atom to which they are attached to form an unsubstituted oxetanyl. [0149] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a. [0150] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³, together with the carbon atom to which they are attached, form a cyclobutyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³, together with the carbon atom to which they are attached, form an unsubstituted C₃-C₆ cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³, together with the carbon atom to which they are attached, form an unsubstituted cyclobutyl. [0151] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³, together with the carbon atom to which they are attached, form a 4- to 7-membered heterocyclyl optionally substituted with 1-4 R^a. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³, together with the carbon atom to which they are attached, form an oxetanyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³, together with the carbon atom to which they are attached, form an unsubstituted 4- to 7-membered heterocyclyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R⁴ is H, R⁵ is H, and R² and R³, together with the carbon atom to which they are attached, form an unsubstituted oxetanyl. [0152] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁵ is H, and R² and R⁴ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁵ is H, and R² and R⁴ are taken together with the atoms to which they are attached to form a cyclopentyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁵ is H, and R² and R⁴ are taken together with the atoms to which they are attached to form an unsubstituted 3- to 6-membered cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁵ is H, and R² and R⁴ are taken together with the atoms to which they are attached to form an unsubstituted cyclopentyl. [0153] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁴ is H, and R² and R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁴ is H, and R² and R⁵ are taken together with the atoms to which they are attached to form a cyclopentyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁴ is H, and R² and R⁵ are taken together with the atoms to which they are attached to form an unsubstituted 3- to 6-membered cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁴ is H, and R² and R⁵ are taken together with the atoms to which they are attached to form an unsubstituted cyclopentyl. [0154] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁵ is H, and R³ and R⁴ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁵ is H, and R³ and R⁴ are taken together with the atoms to which they are attached to form a cyclopentyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁵ is H, and R³ and R⁴ are taken together with the atoms to which they are attached to form an unsubstituted 3- to 6-membered cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁵ is H, and R³ and R⁴ are taken together with the atoms to which they are attached to form an unsubstituted cyclopentyl. [0155] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁴ is H, and R³ and R⁵ are taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁴ is H, and R³ and R⁵ are taken together with the atoms to which they are attached to form a cyclopentyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁴ is H, and R³ and R⁵ are taken together with the atoms to which they are attached to form an unsubstituted 3- to 6-membered cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁴ is H, and R³ and R⁵ are taken together with the atoms to which they are attached to form an unsubstituted cyclopentyl. [0156] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁵ is H, and R² and R⁴, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁵ is H, and R² and R⁴, together with the carbon atoms to which they are attached, form a cyclopentyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁵ is H, and R² and R⁴, together with the carbon atoms to which they are attached, form an unsubstituted C₃-C₆ cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁵ is H, and R² and R⁴, together with the carbon atoms to which they are attached, form an unsubstituted cyclopentyl. [0157] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁴ is H, and R² and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁴ is H, and R² and R⁵, together with the carbon atoms to which they are attached, form a cyclopentyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁴ is H, and R² and R⁵, together with the carbon atoms to which they are attached, form an unsubstituted C₃-C₆ cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R³ is H, R⁴ is H, and R² and R⁵, together with the carbon atoms to which they are attached, form an unsubstituted cyclopentyl. [0158] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁵ is H, and R³ and R⁴, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁵ is H, and R³ and R⁴, together with the carbon atoms to which they are attached, form a cyclopentyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁵ is H, and R³ and R⁴, together with the carbon atoms to which they are attached, form an unsubstituted C₃-C₆ cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁵ is H, and R³ and R⁴, together with the carbon atoms to which they are attached, form an unsubstituted cyclopentyl. [0159] In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁴ is H, and R³ and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁴ is H, and R³ and R⁵, together with the carbon atoms to which they are attached, form a cyclopentyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁴ is H, and R³ and R⁵, together with the carbon atoms to which they are attached, form an unsubstituted C₃-C₆ cycloalkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹ is H, R² is H, R⁴ is H, and R³ and R⁵, together with the carbon atoms to which they are attached, form an unsubstituted cyclopentyl. [0160] In some embodiments, R⁶ is hydrogen, halogen, C₁-C₃ alkyl, phenyl, C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –(CH₂)_mO(CH₂)_m-(C₁-C₃ alkoxy), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(aryl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(heteroaryl), –NH-aryl, –C(O)-(4- to 7-membered heterocyclyl), heteroaryl, 4- to 10-membered heterocyclyl, 3- to 6-membered cycloalkyl, –CH₂S(O)₂CH₃, –CH₂S(O)NCH₃ and cyano. In some embodiments, R⁶ is C₁-C₃ alkyl. In some embodiments, R⁶ is an unsubstituted C₁-C₃ alkyl. In some embodiments, R⁶ is methyl, ethyl, n-propyl, or isopropyl. In some embodiments, R⁶ is a substituted C₁-C₃ alkyl. [0161] In some embodiments, R⁶ is hydrogen. In other embodiments, R⁶ is halogen. In some embodiments, R⁶ is chloro, bromo, fluoro, or iodo. [0162] In some embodiments, R⁶ is phenyl. In some embodiments, the phenyl is a substituted phenyl. In some embodiments, the phenyl is an unsubstituted phenyl. [0163] In some embodiments, R⁶ is –C₁-C₃ alkylene-(4-to 7-membered heterocyclyl). In some embodiments, the C₁-C₃ alkylene is a methylene. In some embodiments, the C₁-C₃ alkylene is an ethylene. In some embodiments, the C₁-C₃ alkylene is a propylene. In some embodiments, the 4- to 7-membered heterocyclyl is a substituted 4- to 7-membered heterocyclyl. In some embodiments, the 4- to 7-membered heterocyclyl is an unsubstituted 4- to 7-membered heterocyclyl. In some embodiments, the heterocyclyl is a 4-membered heterocyclyl. In some embodiments, the heterocyclyl is a 5-membered heterocyclyl. In some embodiments, the heterocyclyl is a 6-membered heterocyclyl. In some embodiments, the heterocyclyl is a 7-membered heterocyclyl. [0164] In some embodiments, R⁶ is –(CH₂)_mO-(C₁-C₆ alkyl). In some embodiments, the C₁-C₆ alkyl is an unsubstituted alkyl. In some embodiments, the C₁-C₆ alkyl is a substituted alkyl. In some embodiments, the C₁-C₆ alkyl is a methyl, ethyl, propyl, butyl, pentyl, or hexyl. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. [0165] In some embodiments, R⁶ is –(CH₂)_mO(CH₂)_m-(C₁-C₃ alkoxy). In some embodiments, each m is selected individually from 0, 1, 2, and 3. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, the alkoxy is a methoxy. In some embodiments, the alkoxy is an ethoxy. In some embodiments, the alkoxy is a propoxy. [0166] In some embodiments, R⁶ is –CH₂O-(C₁-C₆ haloalkyl). In some embodiments, the C₁-C₆ haloalkyl is a C₁ haloalkyl. In some embodiments, the C₁-C₆ haloalkyl is a C₂ haloalkyl. In some embodiments, the C₁-C₆ haloalkyl is a C₃ haloalkyl. In some embodiments, the C₁-C₆ haloalkyl is a C₄ haloalkyl. In some embodiments, the C₁-C₆ haloalkyl is a C₅ haloalkyl. In some embodiments, the C₁-C₆ haloalkyl is a C₆ haloalkyl. [0167] In some embodiments, R⁶ is –CH₂O-(CH₂)_m-(aryl). In some embodiments, the aryl is a substituted aryl. In some embodiments, the aryl is an unsubstituted aryl. In some embodiments, the aryl is phenyl. In some embodiments, the aryl is naphthyl. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. [0168] In some embodiments, R⁶ is cyano. [0169] In some embodiments, R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl). In some embodiments, the 4- to 6-membered heterocyclyl is a substituted heterocycle. In some embodiments, the 4- to 6-membered heterocycle is an unsubstituted heterocycle. In some embodiments, the heterocycle is a 4-membered heterocycle. In some embodiments, the heterocycle is a 5-membered heterocycle. In some embodiments, the heterocycle is a 6-membered heterocycle. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. [0170] In some embodiments, R⁶ is –NH-aryl. In some embodiments, the aryl is a substituted aryl. In some embodiments, the aryl is an unsubstituted aryl. In some embodiments, the aryl is phenyl. In some embodiments, the aryl is naphthyl. [0171] In some embodiments, R⁶ is –C(O)-(4- to 7-membered heterocyclyl). In some embodiments, the 4- to 7-membered heterocyclyl is an unsubstituted heterocyclyl. In some embodiments, the 4- to 7-membered heterocyclyl is a substituted heterocyclyl. In some embodiments, the heterocyclyl is a 4-membered heterocyclyl. In some embodiments, the heterocyclyl is a 5-membered heterocyclyl. In some embodiments, the heterocyclyl is a 6-membered heterocyclyl. In some embodiments, the heterocyclyl is a 7-membered heterocyclyl. [0172] In some embodiments, R⁶ is a 4- to 10-membered heterocyclyl. In some embodiments, the 4- to 10-membered heterocyclyl is a substituted heterocycle. In some embodiments, the 4- to 10-membered heterocycle is an unsubstituted heterocycle. In some embodiments, the heterocycle is a 4-membered heterocycle. In some embodiments, the heterocycle is a 5-membered heterocycle. In some embodiments, the heterocycle is a 6-membered heterocycle. In some embodiments, the heterocycle is a 7-membered heterocycle. In some embodiments, the heterocycle is an 8-membered heterocycle. In some embodiments, the heterocycle is a 9-membered heterocycle. In some embodiments, the heterocycle is a 10-membered heterocycle. [0173] In some embodiments, R⁶ is –CH₂O-(CH₂)_m-(heteroaryl). In some embodiments, the heteroaryl is an unsubstituted heteroaryl. In some embodiments, the heteroaryl is a substituted heteroaryl. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. [0174] In some embodiments, R⁶ is heteroaryl. In some embodiments, the heteroaryl is an unsubstituted heteroaryl. In some embodiments, the heteroaryl is a substituted heteroaryl. In some embodiments, the heteroaryl is substituted with a C₁-C₃ alkyl. [0175] In some embodiments, R⁶ is a 3- to 6-membered cycloalkyl. In some embodiments, the cycloalkyl is a substituted cycloalkyl. In some embodiments, the cycloalkyl is an unsubstituted alkyl. In some embodiments, the cycloalkyl is a 3-membered cycloalkyl. In some embodiments, the cycloalkyl is a 4-membered cycloalkyl. In some embodiments, the cycloalkyl is a 5-membered cycloalkyl. In some embodiments, the cycloalkyl is a 6-membered cycloalkyl. [0176] In some embodiments, R⁶ is –CH₂S(O)₂CH₃. [0177] In some embodiments, R⁶ is –CH₂S(O)NCH₃. [0178] In some embodiments, R⁶ is selected from hydrogen, halogen, CH₃, cyano,

,

embodiments, R⁶ is hydrogen or methyl. [0179] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(heteroaryl), heteroaryl, 4- to 10-membered heterocyclyl, and cyano. [0180] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is selected from hydrogen; halogen; C₁-C₃ alkyl optionally substituted with cyano; –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl) optionally substituted with 1-2 halogen, C₁-C₃ alkoxy, or oxo; –(CH₂)_mO-(C₁-C₆ alkyl); –CH₂O-(C₁-C₆ haloalkyl); –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) optionally substituted with 1 C₁-C₃ alkyl; –CH₂O-(CH₂)_m-(heteroaryl) optionally substituted with 1 C₁-C₃ alkyl; heteroaryl optionally substituted with 1 C₁-C₃ alkyl; 4- to 10-membered heterocyclyl; and cyano. [0181] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl), 5- to 10-membered heteroaryl, 4- to 10-membered heterocyclyl, cyano, and C₁-C₃ cyanoalkyl, wherein said 4- to 10-membered heterocyclyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), or –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) is optionally substituted with 1-4 R^a, and said 5- to 10-membered heteroaryl or –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) is optionally substituted with 1-3 R^b. [0182] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein each R^a is independently selected from halogen, oxo, C₁-C₃ alkoxy, and C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof wherein at least 1 R^a is halogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof wherein at least 1 R^a is oxo. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof wherein at least 1 R^a is C₁-C₃ alkoxy. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof wherein at least 1 R^a is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof wherein each R^a is independently selected from F, oxo, –OCH₃, and –CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof wherein at least 1 R^a is F. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof wherein at least 1 R^a is oxo. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof wherein at least 1 R^a is –OCH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof wherein at least 1 R^a is –CH₃. [0183] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least 1 R^b is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least 1 R^b is –CH₃. [0184] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is hydrogen. [0185] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is halogen. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is Cl. [0186] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is C₁-C₃ alkyl optionally substituted with cyano. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is unsubstituted C₁-C₃ alkyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is C₁-C₃ alkyl substituted with 1 cyano. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂CN. [0187] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl) optionally substituted with 1-4 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl) optionally substituted with 1-2 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl) optionally substituted with 1-4 R^a, wherein each R^a is independently selected from halogen, C₁-C₃ alkoxy, and oxo. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl) optionally substituted with 1-2 R^a, wherein each R^a is independently selected from halogen, C₁-C₃ alkoxy, and oxo. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl) optionally substituted with 1-4 R^a, wherein each R^a is independently selected from F, –OCH₃, and oxo. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl) optionally substituted with 1-2 R^a, wherein each R^a is independently selected from F, –OCH₃, and oxo. [0188] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl) optionally substituted with 1-2 halogen, C₁-C₃ alkoxy, or oxo. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂-(4- to 5-membered heterocyclyl) optionally substituted with 1-2 halogen, C₁-C₃ alkoxy, or oxo. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂-(4- to 5-membered heterocyclyl) substituted with 2 halogen. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂-(4- to 5-membered heterocyclyl) substituted with 1 C₁-C₃ alkoxy. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂-(4- to 5-membered heterocyclyl) substituted with 1 oxo. [0189] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

,

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ i

[0190] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –(CH₂)_mO-(C₁-C₆ alkyl). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –(CH₂)_mO-(C₁-C₆ alkyl) and m is 1 or 2. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂OCH₃, –CH₂OCH₂CH₃, or –CH₂CH₂OCH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂OCH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂OCH₂CH₃. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂CH₂OCH₃. [0191] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(C₁-C₆ haloalkyl). In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂OCH₂CF₃. [0192] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl). In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) optionally substituted with 1 C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) and m is 0 or 1. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) optionally substituted with 1 C₁-C₃ alkyl and m is 0 or 1. [0193] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) optionally substituted with 1-4 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) optionally substituted with 1 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) optionally substituted with 1-4 R^a and m is 0 or 1. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) optionally substituted with 1 R^a and m is 0 or 1. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) optionally substituted with 1-4 R^a, m is 0 or 1, and R^a is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) optionally substituted with 1 R^a, m is 0 or 1, and R^a is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) optionally substituted with 1-4 R^a, m is 0 or 1, and R^a is –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) optionally substituted with 1 R^a, m is 0 or 1, and R^a is –CH₃. [0194] In some embodiments, the invention relates to a compound of formula (I), or a ,

formula (I), or a pharmaceutically acceptable salt thereof, wherein

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ i

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ i

. [0195] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(heteroaryl). In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(heteroaryl) optionally substituted with 1 C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(heteroaryl) and m is 0. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(heteroaryl) optionally substituted with 1 C₁-C₃ alkyl and m is 0. [0196] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) optionally substituted with 1-3 R^b. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) substituted with 1 R^b. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) optionally substituted with 1-3 R^b and m is 0. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) substituted with 1 R^b and m is 0. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) optionally substituted with 1-3 R^b, m is 0, and R^b is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) substituted with 1 R^b, m is 0, and R^b is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) optionally substituted with 1-3 R^b, m is 0, and R^b is –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) substituted with 1 R^b, m is 0, and R^b is –CH₃. [0197] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

. [0198] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is heteroaryl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is heteroaryl optionally substituted with 1 C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is heteroaryl optionally substituted with 1 –CH₃. [0199] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is 5- to 10-membered heteroaryl optionally substituted 1-3 R^b. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is 5- to 10-membered heteroaryl substituted 1 R^b. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is 5- to 10-membered heteroaryl optionally substituted 1-3 R^b and R^b is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is 5- to 10-membered heteroaryl substituted 1 R^b and R^b is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is 5- to 10-membered heteroaryl optionally substituted 1-3 R^b and R^b is –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is 5- to 10-membered heteroaryl substituted 1 R^b and R^b is –CH₃. [0200] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

_. [0201] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is 4- to 10-membered heterocyclyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is an unsubstituted 4- to 10-membered heterocyclyl. [0202] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is 4- to 10-membered heterocyclyl optionally substituted with 1-4 R^a. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is 4- to 10-membered heterocyclyl optionally substituted with 1-2 R^a. [0203] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

[0204] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is cyano. [0205] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is C₁-C₃ cyanoalkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂CN. [0206] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is selected from hydrogen, Cl, –CH₃, –CH₂CN,

,

[0207] In some embodiments, R⁷ is hydrogen, halo, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, –C₁-C₄ alkylene-(C₁-C₃ alkoxy), 3- to 6-membered cycloalkyl, –O-(3- to 6-membered cycloalkyl), –O-heteroaryl, -O-(C₁-C₄ alkylene)-(C₁-C₃ alkoxy), –O-(C₁-C₃ alkoxy)-heteroaryl, –O-(C₁-C₄ alkylene)-(4- to 7-membered heterocyclyl), –O-(C₁-C₄ alkylene)-O-(3- to 6-membered cycloalkyl), –NH-CH₂-heteroaryl, or . In some embodiments, R⁷ is hydrogen. [0208] In some embodiments, R⁷ is halo. In some embodiments, R⁷ is chloro, bromo, fluoro, or iodo. [0209] In some embodiments, R⁷ is a C₁-C₆ alkyl. In some embodiments, the C₁-C₆ alkyl is a substituted alkyl. In some embodiments, the C₁-C₆ alkyl is an unsubstituted alkyl. In some embodiments, the alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tertbutyl, pentyl, or hexyl. [0210] In some embodiments, R⁷ is a C₁-C₆ haloalkyl. In some embodiments, the C₁-C₆ haloalkyl is a C₁ haloalkyl. In some embodiments, the C₁-C₆ haloalkyl is a C₂ haloalkyl. In some embodiments, the C₁-C₆ haloalkyl is a C₃ haloalkyl. In some embodiments, the C₁-C₆ haloalkyl is a C₄ haloalkyl. In some embodiments, the C₁-C₆ haloalkyl is a C₅ haloalkyl. In some embodiments, the C₁-C₆ haloalkyl is a C₆ haloalkyl. [0211] In some embodiments, R⁷ is a C₁-C₆ alkoxy. In some embodiment, the C₁-C₆ alkoxy is a C₁ alkoxy. In some embodiment, the C₁-C₆ alkoxy is a C₂ alkoxy. In some embodiment, the C₁-C₆ alkoxy is a C₃ alkoxy. In some embodiment, the C₁-C₆ alkoxy is a C₄ alkoxy. In some embodiment, the C₁-C₆ alkoxy is a C₅ alkoxy. In some embodiment, the C₁-C₆ alkoxy is a C₆ alkoxy. [0212] In some embodiments, R⁷ is -C₁-C₄ alkylene-(C₁-C₃ alkoxy). In some embodiments, the alkylene is a methylene. In some embodiments, the alkylene is an ethylene. In some embodiments, the alkylene is a propylene. In some embodiments, the alkylene is a butylene. In some embodiments, the alkoxy is methoxy. In some embodiments, the alkoxy is ethoxy. In some embodiments, the alkoxy is propoxy. [0213] In some embodiments, R⁷ is a 3- to 6-membered cycloalkyl. In some embodiments, the cycloalkyl is a substituted cycloalkyl. In some embodiments, the cycloalkyl is an unsubstituted alkyl. In some embodiments, the cycloalkyl is a 3-membered cycloalkyl. In some embodiments, the cycloalkyl is a 4-membered cycloalkyl. In some embodiments, the cycloalkyl is a 5-membered cycloalkyl. In some embodiments, the cycloalkyl is a 6-membered cycloalkyl. [0214] In some embodiments, R⁷ is -O-(3- to 6-membered cycloalkyl). In some embodiments, the cycloalkyl is a substituted cycloalkyl. In some embodiments, the cycloalkyl is an unsubstituted alkyl. In some embodiments, the cycloalkyl is a 3-membered cycloalkyl. In some embodiments, the cycloalkyl is a 4-membered cycloalkyl. In some embodiments, the cycloalkyl is a 5-membered cycloalkyl. In some embodiments, the cycloalkyl is a 6-membered cycloalkyl. [0215] In some embodiments, R⁷ is -O-heteroaryl. In some embodiments, the heteroaryl is an unsubstituted heteroaryl. In some embodiments, the heteroaryl is a substituted heteroaryl. [0216] In some embodiments, R⁷ is -O-(C₁-C₄ alkylene)-(C₁-C₃ alkoxy). In some embodiments, the alkylene is a methylene. In some embodiments, the alkylene is an ethylene. In some embodiments, the alkylene is a propylene. In some embodiments, the alkylene is a butylene. In some embodiments, the alkoxy is methoxy. In some embodiments, the alkoxy is ethoxy. In some embodiments, the alkoxy is propoxy. [0217] In some embodiments, R⁷ is -O-(C₁-C₃ alkoxy)-heteroaryl. In some embodiments, the alkoxy is methoxy. In some embodiments, the alkoxy is ethoxy. In some embodiments, the alkoxy is propoxy. In some embodiments, the heteroaryl is a substituted heteroaryl. In some embodiments, the heteroaryl is an unsubstituted heteroaryl. [0218] In some embodiments, R⁷ is -O-(C₁-C₄ alkylene)-(4- to 7-membered heterocyclyl). In some embodiments, the alkylene is a methylene. In some embodiments, the alkylene is an ethylene. In some embodiments, the alkylene is a propylene. In some embodiments, the alkylene is a butylene. In some embodiments, the 4- to 7-membered heterocyclyl is an unsubstituted heterocyclyl. In some embodiments, the 4- to 7-membered heterocyclyl is a substituted heterocyclyl. In some embodiments, the heterocyclyl is a 4-membered heterocyclyl. In some embodiments, the heterocyclyl is a 5-membered heterocyclyl. In some embodiments, the heterocyclyl is a 6-membered heterocyclyl. In some embodiments, the heterocyclyl is a 7-membered heterocyclyl. [0219] In some embodiments, R⁷ is -O-(C₁-C₄ alkylene)-O-(3- to 6-membered cycloalkyl). In some embodiments, the alkylene is a methylene. In some embodiments, the alkylene is an ethylene. In some embodiments, the alkylene is a propylene. In some embodiments, the alkylene is a butylene. In some embodiments, the cycloalkyl is a substituted cycloalkyl. In some embodiments, the cycloalkyl is an unsubstituted alkyl. In some embodiments, the cycloalkyl is a 3-membered cycloalkyl. In some embodiments, the cycloalkyl is a 4-membered cycloalkyl. In some embodiments, the cycloalkyl is a 5-membered cycloalkyl. In some embodiments, the cycloalkyl is a 6-membered cycloalkyl. [0220] In some embodiments, R⁷ is -NH-CH₂-heteroaryl. In some embodiments, the heteroaryl is a substituted heteroaryl. In some embodiments, the heteroaryl is an unsubstituted heteroaryl. [0221] In some embodiments, R⁷ is -O-CH₂-heteroaryl. In some embodiments, the heteroaryl is an unsubstituted heteroaryl. In some embodiments, the heteroaryl is a substituted heteroaryl. In some embodiments,

. [0222] In some embodiments, R⁷ is . In some embodiments, R¹⁰ is heterocyclyl, cycloalkyl, or heteroaryl. In some embodiments, R¹⁰ is a substituted heterocyclyl. In some embodiments, R¹⁰ is an unsubstituted heterocyclyl. In some embodiments, the heterocyclyl is a 4- to 6-membered heterocyclyl. In some embodiments, R¹⁰ is a substituted cycloalkyl. In some embodiments, R¹⁰ is an unsubstituted cycloalkyl. In some embodiments, the cycloalkyl is a 4- to 6-membered cycloalkyl. In some embodiments, R¹⁰ is a substituted heteroaryl. In some embodiments, R¹⁰ is an unsubstituted heteroaryl. In some embodiments, the heteroaryl is a 5- to 10-membered heteroaryl. In some embodiments,

[0223] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is selected from hydrogen, halogen, and . [0224] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is heteroaryl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is 5- to 10-membered heteroaryl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is heteroaryl optionally substituted with 1-3 C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is heteroaryl optionally substituted with 1-3 –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 –CH₃. [0225] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1-3 R^b. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 R^b. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1-3 R^b and each R^b is independently C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 R^b and R^b is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1-3 R^b and each R^b is –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 R^b and R^b is –CH₃. [0226] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is hydrogen. [0227] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is halogen. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is F. [0228] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is . [0229] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is and R¹⁰ is heteroaryl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is and R¹⁰ is heteroaryl optionally substituted with 1-3 C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is and R¹⁰ is heteroaryl optionally substituted with 1 C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is

and R¹⁰ is heteroaryl optionally substituted with 1-3 –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is

and R¹⁰ is heteroaryl optionally substituted with 1 –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is and R¹⁰ is 5- to 10-membered heteroaryl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷

and R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1-3 C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is

and R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is and R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1-3 –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is

and R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 –CH₃. [0230] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is and R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1-3 R^b. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is

and R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 R^b. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is and R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1-3 R^b and each R^b is independently C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is and R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 R^b and R^b is C₁-C₃ alkyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is and R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1-3 R^b and R^b is –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is and R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 R^b and R^b is –CH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically _{acceptable salt thereof, wherein}

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

. [0231] In some embodiments, the invention relates to formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is selected from hydrogen,

. [0232] In some embodiments, R⁸ is hydrogen. [0233] In some embodiments, R⁸ is C₁-C₃ alkyl. In some embodiments, the alkyl is a substituted alkyl. In some embodiments, the alkyl is an unsubstituted alkyl. In some embodiments, R⁸ is methyl, ethyl, n-propyl, or isopropyl. [0234] In some embodiments, R⁸ is a C₁-C₆ haloalkyl. In some embodiments, the haloalkyl is a C₁ haloalkyl. In some embodiments, the haloalkyl is a C₂ haloalkyl. In some embodiments, the haloalkyl is a C₃ haloalkyl. In some embodiments, the haloalkyl is a C₄ haloalkyl. In some embodiments, the haloalkyl is a C₅ haloalkyl. In some embodiments, the haloalkyl is a C₆ haloalkyl. [0235] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁸ is hydrogen. [0236] In some embodiments, R⁷ and R⁸ are taken together to form a fused bicyclic heteroaromatic ring. In some embodiments, the fused bicyclic heteroaromatic ring is a substituted fused bicyclic heteroaromatic ring. In some embodiments, the fused bicyclic heteroaromatic ring is an unsubstituted fused bicyclic heteroaromatic ring. In some embodiments, R⁷ and R⁸ are taken together with the ,

[0237] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together to form a fused bicyclic heteroaromatic ring. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together to form a fused bicyclic heteroaromatic ring optionally substituted with 1-3 C₁-C₃ alkoxy. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together to form a fused bicyclic heteroaromatic ring optionally substituted with 1 C₁-C₃ alkoxy. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together to form a fused bicyclic heteroaromatic ring optionally substituted with 1-3 –OCH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together to form a fused bicyclic heteroaromatic ring optionally substituted with 1 –OCH₃. [0238] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1-3 R^c. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1 R^c. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1-3 R^c and each R^c is independently selected from C₁-C₃ alkoxy. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1 R^c and R^c is C₁-C₃ alkoxy. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1-3 R^c and R^c is –OCH₃. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1 R^c and R^c is –OCH₃. [0239] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused furanyl, thiophenyl, thiazolyl, or pyridinyl, each of which may be optionally substituted with 1 C1-C₃ alkoxy. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused furanyl optionally substituted with 1 C1-C₃ alkoxy. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused thiophenyl optionally substituted with 1 C1-C₃ alkoxy. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused thiazolyl optionally substituted with 1 C1-C₃ alkoxy. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused pyridinyl optionally substituted with 1 C1-C₃ alkoxy. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form an unsubstituted fused furanyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form an unsubstituted fused thiophenyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form an unsubstituted fused thiazolyl. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused pyridinyl substituted with 1 C1-C₃ alkoxy. [0240] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form

,

some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form . In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form . In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form

. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form

. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form

. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form

. [0241] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is CH, R⁷ is H, and R⁸ is H. [0242] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is CH, R⁷ is halogen, and R⁸ is H. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is CH, R⁷ is F, and R⁸ is H. [0243] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is CH, R⁷ is , and R⁸ is H. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt _{thereof, wherein}

other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is

embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein

H. [0244] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is CH, and R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1-3 R^c. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is CH, and R⁷ and R⁸, together with the carbon atoms to which they are attached, form an unsubstituted fused furanyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is CH, and R⁷ and R⁸, together with the carbon atoms to which they are attached, form an unsubstituted fused thiophenyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is CH, and R⁷ and R⁸, together with the carbon atoms to which they are attached, form an unsubstituted fused thiazolyl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is CH, and R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused pyridinyl substituted with one –OCH₃. [0245] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is N, R⁷ is H, and R⁸ is H. [0246] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is N, and R⁷ and R⁸, together with the carbon atoms to which they are attached, form an unsubstituted fused thiophenyl. [0247] In some embodiments, the invention relates to a compound of formula (I), wherein the compound is of formula (I-A):

or a pharmaceutically acceptable salt thereof. [0248] In some embodiments, the invention relates to a compound of formula (I), wherein the compound is of formula (I-B):

or a pharmaceutically acceptable salt thereof, wherein: Ring A is C₆-C₁₀ aryl or 5- to 10-membered heteroaryl; R² is hydrogen or C₁-C₆ alkyl; R³ is hydrogen or C₁-C₆ alkyl; or R² and R³, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl; R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl), 5- to 10-membered heteroaryl, 4- to 10-membered heterocyclyl, cyano, and C₁-C₃ cyanoalkyl, wherein said –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl) or –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) is optionally substituted with 1-2 R^a, and said 5- to 10-membered heteroaryl or –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) is optionally substituted with 1 R^b; R⁷ is selected from hydrogen, halogen, and ; R⁸ is hydrogen; or R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1 R^c; each R⁹ is independently selected from the group consisting of halogen, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, and –O-(C₁-C₃ haloalkyl); R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 R^b; each R^a is independently selected from halogen, oxo, C₁-C₃ alkyl, and C₁-C₃ alkoxy; each R^b is independently selected from C₁-C₃ alkyl; R^c is C₁-C₃ alkoxy; each m is independently 0, 1, or 2; and n is 0, 1, or 2. [0249] In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein Ring A is C₆-C₁₀ aryl. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl. [0250] In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein Ring A is a 5- to 10-membered heteroaryl. In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from phenyl, benzo[d]isothiazol-3-yl, benzo[d]thiazol-4-yl, and quinolin-8-yl. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein Ring A is benzo[d]isothiazol-3-yl. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein Ring A is benzo[d]thiazol-4-yl. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein Ring A is quinolin-8-yl. [0251] In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein n is 0. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein n is 1. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein n is 2. [0252] In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein each R⁹ is independently selected from the group consisting of Cl, F, –CH₃, –CH₂CH₃, –OCH₃, –CF₃, and –OCHF₂. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is Cl. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is F. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –CH₃. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –CH₂CH₃. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –OCH₃. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –CF₃. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –OCHF₂. [0253] In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R² is hydrogen or –CH₃. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R² is hydrogen. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R² is –CH₃. [0254] In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R³ is hydrogen or –CH₃. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R³ is hydrogen. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R³ is –CH₃. [0255] In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form an unsubstituted cyclobutyl or oxetanyl. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form an unsubstituted cyclobutyl. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form an unsubstituted oxetanyl. [0256] In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is selected from hydrogen, Cl, –CH₃, –CH₂CN,

_, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is hydrogen. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is Cl. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₃. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂CN. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂OCH₃. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂OCH₂CH₃. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂CH₂OCH₃. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂OCH₂CF₃. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein

some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

_{. In some embodiments, the invention relates to a compound of formula (I-B), or a} pharmaceutically acceptable salt thereof, wherein

some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁶ is cyano. [0257] In some embodiments, the invention relates to a compound of formula (I-B), or a _{pharmaceutically acceptable salt thereof, wherein R} ⁷ _{is selected from hydrogen,}

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ is hydrogen. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ is F. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein

. [0258] In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁸ is hydrogen. [0259] In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form an unsubstituted fused furanyl, an unsubstituted fused thiophenyl, an unsubstituted fused thiazolyl, or a fused pyridinyl substituted with 1 –OCH₃. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form an unsubstituted fused furanyl. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form an unsubstituted fused thiophenyl. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form an unsubstituted fused thiazolyl. In other embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused pyridinyl substituted with 1 –OCH₃. [0260] In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic

some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form

. In some embodiments, the invention relates to a compound of formula (I-B), or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form

. [0261] In some embodiments, the invention relates to a compound of formula (I), wherein the compound is of formula (I-C):

or a pharmaceutically acceptable salt thereof, wherein: R² is hydrogen or C₁-C₆ alkyl; R³ is hydrogen or C₁-C₆ alkyl; or R² and R³, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl; R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl), 5- to 10-membered heteroaryl, 4- to 10-membered heterocyclyl, cyano, and C₁-C₃ cyanoalkyl, wherein said –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl) or –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) is optionally substituted with 1-2 R^a, and said 5- to 10-membered heteroaryl or –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) is optionally substituted with 1 R^b; R⁷ is selected from hydrogen, halogen, and ; each R⁹ is independently selected from the group consisting of halogen, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, and –O-(C₁-C₃ haloalkyl); R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1 R^b; each R^a is independently selected from halogen, oxo, C₁-C₃ alkyl, and C₁-C₃ alkoxy; each R^b is independently selected from C₁-C₃ alkyl; each m is independently 0, 1, or 2; and n is 0, 1, or 2. [0262] In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein n is 0. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein n is 1. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein n is 2. [0263] In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein each R⁹ is independently selected from the group consisting of Cl, F, –CH₃, –CH₂CH₃, –OCH₃, –CF₃, and –OCHF₂. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is Cl. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is F. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –CH₃. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –CH₂CH₃. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –OCH₃. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –CF₃. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein at least 1 R⁹ is –OCHF₂. [0264] In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R² is hydrogen or –CH₃. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R² is hydrogen. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R² is –CH₃. [0265] In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R³ is hydrogen or –CH₃. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R³ is hydrogen. In other embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R³ is –CH₃. [0266] In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form an unsubstituted cyclobutyl or oxetanyl. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form an unsubstituted cyclobutyl. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form an unsubstituted oxetanyl. [0267] In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is selected from hydrogen, Cl, –CH₃, –CH₂CN,

_, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is hydrogen. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is Cl. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₃. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂CN. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is . In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂OCH₃. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂OCH₂CH₃. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂CH₂OCH₃. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is –CH₂OCH₂CF₃. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein

. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein

. In some embodiments, the inven

relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein

some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is

. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein

some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein

some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein

some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein

_{. In some embodiments, the invention relates to a compound of formula (I-C), or a} pharmaceutically acceptable salt thereof, wherein

some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁶ is cyano. [0268] In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁷ is selected from hydrogen,

. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁷ is hydrogen. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein R⁷ is F. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically _{acceptable salt thereof, wherein}

. In some embodiments, the invention relates to a compound of formula (I-C), or a pharmaceutically acceptable salt thereof, wherein

. [ :

,

,

[0270] In some embodiments, the invention relates to a compound selected from the group consisting of:

, ,

or a pharmaceutically acceptable salt thereof. [0271] In some embodiments, the invention relates to a compound selected from Table A, or a pharmaceutically acceptable salt thereof. In other embodiments, the invention relates to a compound selected from Table A, i.e., the compound in non-salt form. [0272] Table A. Exemplary Compounds of the Invention.

[0273] In some embodiments, the invention relates to a compound selected from Table B, or a pharmaceutically acceptable salt thereof. In other embodiments, the invention relates to a compound selected from Table B, i.e., the compound in non-salt form. [0274] Table B. Additional Compounds of the Invention.

[0275] In one embodiment, the compound is a compound selected from Examples 1-14. [0276] In one embodiment, the compound is a compound selected from Examples 1 to 77, or a pharmaceutically acceptable salt thereof. In other embodiments, the invention relates to a compound selected from Examples 1 to 77, i.e. the compound in non-salt form. [0277] In some embodiments, the invention relates to a compound selected from Table A, Table B, or Examples 1 to 77, or a pharmaceutically acceptable salt thereof. In other embodiments, the invention relates to a compound selected from Table A, Table B, or Examples 1 to 77, i.e. the compound in non-salt form. B. Radiolabeled Analogs of the Compounds of the Invention [0278] In another aspect, the invention relates to radiolabeled analogs of the compounds of the invention. As used herein, the term “radiolabeled analogs of the compounds of the invention” refers to compounds that are identical to the compounds of the invention, as described herein, including all embodiments thereof, except that one or more atoms has been replaced with a radioisotope of the atom present in the compounds of the invention. [0279] As used herein, the term “radioisotope” refers to an isotope of an element that is known to undergo spontaneous radioactive decay. Examples of radioisotopes include ³H, ¹⁴C, ³²P, ³⁵S, ¹⁸F, ³⁶Cl, and the like, as well as the isotopes for which a decay mode is identified in V.S. Shirley & C.M. Lederer, Isotopes Project, Nuclear Science Division, Lawrence Berkeley Laboratory, Table of Nuclides (January 1980). [0280] The radiolabeled analogs can be used in a number of beneficial ways, including in various types of assays, such as substrate tissue distribution assays. For example, tritium (³H)- and/or carbon-14 (¹⁴C)-labeled compounds may be useful for various types of assays, such as substrate tissue distribution assays, due to relatively simple preparation and excellent detectability. [0281] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein one or more of R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, or R⁹ is D, a deuterated C₁-C₆ alkyl (e.g. –CD₃), or a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein one or more of R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, or R⁹ is D. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein one or more of R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, or R⁹ is a deuterated C₁-C₆ alkyl (e.g. –CD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein one or more of R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, or R⁹ is a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). [0282] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is D, a deuterated C₁-C₆ alkyl (e.g. –CD₃), or a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is D. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is a deuterated C₁-C₆ alkyl (e.g. –CD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). [0283] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is D, a deuterated C₁-C₆ alkyl (e.g. –CD₃), or a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is D. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is a deuterated C₁-C₆ alkyl (e.g. –CD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R³ is a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). [0284] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is D, a deuterated C₁-C₆ alkyl (e.g. –CD₃), or a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is D. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is a deuterated C₁-C₆ alkyl (e.g. –CD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁴ is a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). [0285] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is D, a deuterated C₁-C₆ alkyl (e.g. –CD₃), or a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is D. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is a deuterated C₁-C₆ alkyl (e.g. –CD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁵ is a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). [0286] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is D, a deuterated C₁-C₆ alkyl (e.g. –CD₃), or a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is D. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is a deuterated C₁-C₆ alkyl (e.g. –CD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁶ is a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). [0287] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is D, a deuterated C₁-C₆ alkyl (e.g. –CD₃), or a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is D. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is a deuterated C₁-C₆ alkyl (e.g. –CD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁷ is a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). [0288] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁸ is D, a deuterated C₁-C₆ alkyl (e.g. –CD₃), or a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁸ is D. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁸ is a deuterated C₁-C₆ alkyl (e.g. –CD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁸ is a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). [0289] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁹ is D, a deuterated C₁-C₆ alkyl (e.g. –CD₃), or a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁹ is D. In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁹ is a deuterated C₁-C₆ alkyl (e.g. –CD₃). In other embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R⁹ is a deuterated C₁-C₆ alkoxy (e.g. –OCD₃). [0290] In some embodiments, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein at least one R^a is –OCD₃. [0291] In another aspect, the invention relates to pharmaceutically acceptable salts of the radiolabeled analogs, in accordance with any of the embodiments described herein in connection with the compounds of the invention. [0292] In another aspect, the invention relates to pharmaceutical compositions comprising the radiolabeled analogs, or pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle, in accordance with any of the embodiments described herein in connection with the compounds of the invention. [0293] In another aspect, the invention relates to methods of inhibiting EGFR and methods of treating or lessening the severity of various diseases and disorders, including various cancers, in a subject comprising administering an effective amount of the radiolabeled analogs, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, in accordance with any of the embodiments described herein in connection with the compounds of the invention. [0294] In another aspect, the invention relates to radiolabeled analogs, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, for use, in accordance with any of the embodiments described herein in connection with the compounds of the invention. [0295] In another aspect, the invention relates to the use of the radiolabeled analogs, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, for the manufacture of medicaments, in accordance with any of the embodiments described herein in connection with the compounds of the invention. [0296] In another aspect, the radiolabeled analogs, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, can be employed in combination therapies, in accordance with any of the embodiments described herein in connection with the compounds of the invention. IV. MODES OF ADMINISTRATION A. Pharmaceutical Compositions [0297] While it may be possible for the compounds disclosed herein to be administered as the raw chemical, it is also possible to present them as a pharmaceutical composition (i.e., as a formulation). Accordingly, provided herein are pharmaceutical compositions which comprise one or more of the compounds disclosed herein, or one or more pharmaceutically acceptable salts, esters, prodrugs, amides, or solvates thereof, together with one or more pharmaceutically acceptable carriers and optionally one or more other therapeutic ingredients. The carrier(s) should be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. Proper formulation is dependent upon the route of administration chosen. Any of the well-known techniques, carriers, and excipients may be used as suitable and as understood in the art; e.g., in Remington's Pharmaceutical Sciences. The pharmaceutical compositions disclosed herein may be manufactured in any manner known in the art, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or compression processes. [0298] In an aspect, provided herein is a pharmaceutical composition including a compound of of the invention, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. Pharmaceutical compositions containing a compound of the invention or a pharmaceutically acceptable salt thereof as the active ingredient can be prepared by intimately mixing the compound of the invention, or a pharmaceutically acceptable salt thereof, with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier can take a wide variety of forms depending upon the desired route of administration (e.g., oral, parenteral). [0299] The pharmaceutical compositions and methods of the present disclosure may be utilized to treat an individual in need thereof. In embodiments, the individual is a mammal such as a human, or a non-human mammal. When administered to an animal, such as a human, the composition or the compound is preferably administered as a pharmaceutical composition including, for example, a compound of the invention and a pharmaceutically acceptable carrier and/or excipient. Pharmaceutically acceptable carriers and excipients are well known in the art and include, for example, aqueous solutions such as water or physiologically buffered saline or other solvents or vehicles such as glycols, glycerol, oils such as olive oil, or injectable organic esters. In preferred embodiments, when such pharmaceutical compositions are for human administration, particularly for invasive routes of administration (i.e., routes, such as injection or implantation, that circumvent transport or diffusion through an epithelial barrier), the aqueous solution is pyrogen-free, or substantially pyrogen-free. The excipients can be chosen, for example, to effect delayed release of an agent or to selectively target one or more cells, tissues, or organs. The pharmaceutical composition can be in dosage unit form such as tablet, capsule (including sprinkle capsule and gelatin capsule), granule, lyophiles for reconstitution, powder, solution, syrup, suppository, injection, or the like. The composition can also be present in a transdermal delivery system, e.g., a skin patch. The composition can also be present in a solution suitable for topical administration, such as a lotion, cream, or ointment. [0300] A pharmaceutically acceptable carrier can contain physiologically acceptable agents that act, for example, to stabilize, increase solubility or to increase the absorption of a compound. Such physiologically acceptable agents include, for example, carbohydrates, such as glucose, sucrose or dextrans, antioxidants, such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins or other stabilizers or excipients. The choice of a pharmaceutically acceptable carrier, including a physiologically acceptable agent, depends, for example, on the route of administration of the composition. The preparation or pharmaceutical composition can be a self-emulsifying drug delivery system or a self microemulsifying drug delivery system. The pharmaceutical composition (preparation) also can be a liposome or other polymer matrix, which can have incorporated therein, for example, a compound of the invention. Liposomes, for example, which comprise phospholipids or other lipids, are nontoxic, physiologically acceptable, and metabolizable carriers that are relatively simple to make and administer. [0301] The phrase "pharmaceutically acceptable" is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. [0302] The phrase "pharmaceutically acceptable carrier" as used herein means a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil, (10) glycols, such as propylene glycol; ( 11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; ( 12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations. [0303] A pharmaceutical composition (preparation) can be administered to a subject by any of a number of routes of administration including, for example, orally (for example, drenches as in aqueous or non-aqueous solutions or suspensions, tablets, capsules (including sprinkle capsules and gelatin capsules), boluses, powders, granules, pastes for application to the tongue); absorption through the oral mucosa (e.g., sublingually); subcutaneously; transdermally (for example as a patch applied to the skin); and topically (for example, as a cream, ointment or spray applied to the skin). The compound may also be formulated for inhalation. In embodiments, a compound may be simply dissolved or suspended in sterile water. Details of appropriate routes of administration and compositions suitable for same can be found in, for example, U.S. Pat. Nos.6, 110,973, 5,763,493, 5,731,000, 5,541,231, 5,427,798, 5,358,970 and 4,172,896, as well as in patents and published applications cited therein. [0304] The formulations may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will vary depending upon the host being treated, the particular mode of administration. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound that produces a therapeutic effect. Generally, out of one hundred percent, this amount will range from about 1 percent to about ninety-nine percent of active ingredient, preferably from about 5 percent to about 70 percent, most preferably from about 10 percent to about 30 percent. [0305] Formulations of the compounds disclosed herein suitable for oral administration may be in the form of capsules (including sprinkle capsules and gelatin capsules), cachets, pills, tablets, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), lyophile, powders, granules, or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia) and/or as mouth washes and the like, each containing a predetermined amount of a compound of the present disclosure as an active ingredient. Compositions or compounds may also be administered as a bolus, electuary, or paste. [0306] Solid dosage forms for oral administration (e.g., capsules (including sprinkle capsules and gelatin capsules), tablets, pills, dragees, powders, granules and the like), may include the active ingredient mixed with one or more pharmaceutically acceptable earners, such as sodium citrate or dicalcium phosphate, and/or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; (2) binders, such as. for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds; (7) wetting agents, such as, for example, cetyl alcohol and glycerol monostearate; (8) absorbents, such as kaolin and bentonite clay; (9) lubricants, such a talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; (50) complexing agents, such as, modified and unmodified cyclodextrins; and (11) coloring agents. In the case of capsules (e.g., sprinkle capsules and gelatin capsules), tablets, and pills, the pharmaceutical compositions may also include buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like. [0307] Compressed tablets may be prepared using binders (for example, gelatin or hydroxypropylmethyl cellulose), lubricants, inert diluents, preservatives, disintegrants (for example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), and/or surface- active or dispersing agents. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. [0308] The tablets, and other solid dosage forms of the pharmaceutical compositions, such as dragees, capsules, pills and granules, may be prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical-formulating art. They may also be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and/or microspheres. They may be sterilized by, for example, filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved in sterile water, or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredients) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. The active ingredient can also be in micro-encapsulated form, if appropriate, with one or more of the above-described excipients. [0309] Liquid dosage forms useful for oral administration include pharmaceutically acceptable emulsions, lyophiles for reconstitution, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active ingredient, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, cyclodextrins and derivatives thereof, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3- butylene glycol, oils (in particular, cottonseed, groundnut, com, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. [0310] Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming, and preservative agents. [0311] Suspensions, in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof. [0312] Dosage forms for the topical or transdermal administration include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants. The active compound may be mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants that may be required. [0313] The ointments, pastes, creams, and gels may contain, in addition to an active compound, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. [0314] Powders and sprays can contain, in addition to an active compound, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbon s and volatile unsubstituted hydrocarbons, such as butane and propane. [0315] The phrases "parenteral administration" and "administered parenterally" as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrastemal injection and infusion. Pharmaceutical compositions suitable for parenteral administration comprise one or more active compounds in combination with one or more pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, or sterile powders which may be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain antioxidants, buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the intended recipient or suspending or thickening agents. [0316] Examples of suitable aqueous and non-aqueous carriers that may be employed in the pharmaceutical compositions include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. [0317] These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like into the compositions. In addition, prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents that delay absorption such as aluminum monostearate and gelatin. [0318] For use in the methods of this invention, active compounds can be given per se or as a pharmaceutical composition containing, for example, 0.1 to 99.5% (more preferably, 0.5 to 90%) of active ingredient in combination with a pharmaceutically acceptable carrier. [0319] Actual dosage levels of the active ingredients in the pharmaceutical compositions may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. [0320] The selected dosage level will depend upon a variety of factors including the activity of the particular compound or combination of compounds employed, or the ester, salt or amide thereof) the route of administration, the time of administration, the rate of excretion of the particular compound(s) being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compound(s) employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. B. Combination Therapies [0321] In certain instances, it may be appropriate to administer at least one of the compounds described herein (or a pharmaceutically acceptable salt, ester, or prodrug thereof) in combination with one or more additional therapeutic agent. In some embodiments, the additional therapeutic agent includes an anti-cancer agent. The anti-cancer agent may be a chemotherapeutic, radiation, or surgical removal of the cancer. [0322] In any case, the multiple therapeutic agents (at least one of which is a compound of the various embodiments disclosed herein) may be administered in any order or even simultaneously. If simultaneously, the multiple therapeutic agents may be provided in a single, unified form, or in multiple forms (by way of example only, either as a single pill or as two separate pills). One of the therapeutic agents may be given in multiple doses, or both may be given as multiple doses. If not simultaneous, the timing between the multiple doses may be any duration of time ranging from a few minutes to four weeks. [0323] In some embodiments, the one or more additional therapies or therapeutic agents are independently selected from: secondary EGFR inhibitors (e.g., afatinib, erlotinib, gefitinib, lapatinib, cetuximab, panitumumab, osimertinib, and olmutinib), ErbB2/Her2 inhibitors (e.g., afatinib, lapatinib, trastuzumab, and pertuzumab), ALK inhibitors (e.g., crizotinib, alectinib, entrectinib, brigatinib), ROS1 inhibitors (e.g., crizotinib, entrectinib, lorlatinib, ceritinib, and merestinib), MEK inhibitors (e.g., trametinib, cobimetinib, binimetinib, selumetinib, refametinib), RAS (KRas, HRas, and/or NRas) inhibitors (e.g., MRTX849, LY3499446, JNJ-74699157, AMG 510, and AZD4785), Bcr-Abl inhibitors (e.g., imatinib, dasatinib, nilotinib), FGFR1, 2, or 3 inhibitors (e.g., nintedanib), MET inhibitors (e.g., capmatinib), AXL inhibitors (e.g., sitravatinib), RET inhibitors (e.g., sunitinib and selpercatinib), ERK inhibitors (e.g., ulixertinib), Shp2 inhibitors (e.g., RLY-1971, RMC-4630, TNO155, and JAB-3068), Bcl-2 inhibitors (e.g., ABT-263, obatoclax, ABT-737, and navitoclax), mTOR inhibitors (e.g., everolimus and tacrolimus), Trk inhibitors (e.g., larotrectinib and entrectinib), checkpoint inhibitors (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and pidilizumab) or other immunotherapies (e.g., monoclonal antibodies), PARP inhibitors (e.g., olaparib), PI3K inhibitors (e.g., buparlisib), BET inhibitors (e.g., GSK1210151A), Raf inhibitors (e.g., encorafenib), MCL-1 inhibitors (e.g., AZD5991), AKT inhibitors (e.g., miltefosine), PDK1 inhibitors (e.g., GSK 2334470), and other chemotherapeutic agents such as taxanes (e.g., paclitaxel and docetaxel), platinum-based agents (e.g., cisplatin and carboplatin), cytoxic agents (e.g., 5-fluorouracil, capecitabine, floxuridine, cytarabine, and gemcitabine), farnesyltransferase inhibitors, topoisomerase inhibitors (e.g., topotecan and irinotecan), DNA synthesis inhibitors (e.g., capecitabine (Xeloda®) and gemcitabine hydrochloride (Gemzar®)), alkylating agents (e.g., temozolomide (Temodar® and Temodal®), dactinomycin (also known as actinomycin-D, Cosmegen®), carmustine (BiCNU®), bendamustine (Treanda®), and lomustine (CeeNU®)), and cytotoxic agents (e.g., vincristine, cytarabine, and pemetrexed). [0324] Epidermal growth factor receptor (EGFR) inhibitors such as osimertinib (AZD9291, merelectinib, TAGRISSO®), erlotinib (TARCEVA®), gefitinib (IRESSA®), cetuximab (ERBITUX®), necitumumab (PORTRAZZA®, IMC-11F8), neratinib (HKI-272, NERLYNX®), lapatinib (TYKERB®), panitumumab (ABX-EGF, VECTIBIX®), vandetanib (CAPRELSA®), rociletinib (CO-1686), olmutinib (OLITA®, HM61713, BI-1482694), naquotinib (ASP8273), nazartinib (EGF816, NVS-816), PF-06747775, icotinib (BPI-2009H), afatinib (BIBW 2992, GILOTRIF®), dacomitinib (PF-00299804, PF-804, PF-299, PF-299804), avitinib (AC0010), AC0010MA EAI045, matuzumab (EMD-7200), nimotuzumab (h-R3, BIOMAb EGFR®), zalutumab, MDX447, depatuxizumab (humanized mAb 806, ABT-806), depatuxizumab mafodotin (ABT-414), ABT-806, mAb 806, canertinib (CI-1033), shikonin, shikonin derivatives (e.g., deoxyshikonin, isobutyrylshikonin, acetylshikonin, β,β-dimethylacrylshikonin and acetylalkannin), poziotinib (NOV120101, HM781-36B), AV-412, ibrutinib, WZ4002, brigatinib (AP26113, ALUNBRIG®), pelitinib (EKB-569), tarloxotinib (TH-4000, PR610), BPI-15086, Hemay022, ZN-e4, tesevatinib (KD019, XL647), YH25448, epitinib (HMPL-813), CK-101, MM-151, AZD3759, ZD6474, PF-06459988, varlintinib (ASLAN001, ARRY-334543), AP32788, HLX07, D-0316, AEE788, HS-10296, avitinib, GW572016, pyrotinib (SHR1258), SCT200, CPGJ602, Sym004, MAb-425, Modotuximab (TAB-H49), futuximab (992 DS), zalutumumab, KL-140, RO5083945, IMGN289, JNJ-61186372, LY3164530, Sym013, AMG 595, BDTX-189, avatinib, Disruptin, CL-387785, EGFRBi-Armed Autologous T Cells, and EGFR CAR-T Therapy. In some embodiments, the additional EGFR-targeted therapeutic agent is selected from osimertinib, gefitinib, erlotinib, afatinib, lapatinib, neratinib, AZD-9291, CL-387785, CO-1686, or WZ4002. [0325] In some aspects, the invention relates to a method of treating any of the diseases or disorders disclosed herein in a subject, wherein said subject is treated with one or more additional therapeutic agents administered concurrently with, prior to, or subsequent to treatment with the compound, pharmaceutically acceptable salt, or pharmaceutical composition. In other aspects, the one or more additional therapeutic agents includes osimertinib (AZD9291, merelectinib, TAGRISSO®), erlotinib (TARCEVA®), gefitinib (IRESSA®), cetuximab (ERBITUX®), necitumumab (PORTRAZZA®, IMC-11F8), neratinib (HKI-272, NERLYNX®), lapatinib (TYKERB®), panitumumab (ABX-EGF, VECTIBIX®), vandetanib (CAPRELSA®), rociletinib (CO-1686), olmutinib (OLITA®, HM61713, BI-1482694), naquotinib (ASP8273), nazartinib (EGF816, NVS-816), PF-06747775, icotinib (BPI-2009H), afatinib (BIBW 2992, GILOTRIF®), dacomitinib (PF-00299804, PF-804, PF-299, PF-299804), avitinib (AC0010), AC0010MA EAI045, matuzumab (EMD-7200), nimotuzumab (h-R3, BIOMAb EGFR®), zalutumab, MDX447, depatuxizumab (humanized mAb 806, ABT-806), depatuxizumab mafodotin (ABT-414), ABT-806, mAb 806, canertinib (CI-1033), shikonin, shikonin derivatives (e.g., deoxyshikonin, isobutyrylshikonin, acetylshikonin, β,β-dimethylacrylshikonin and acetylalkannin), poziotinib (NOV120101, HM781-36B), AV-412, ibrutinib, WZ4002, brigatinib (AP26113, ALUNBRIG®), pelitinib (EKB-569), tarloxotinib (TH-4000, PR610), BPI-15086, Hemay022, ZN-e4, tesevatinib (KD019, XL647), YH25448, epitinib (HMPL-813), CK-101, MM-151, AZD3759, ZD6474, PF-06459988, varlintinib (ASLAN001, ARRY-334543), AP32788, HLX07, D-0316, AEE788, HS-10296, avitinib, GW572016, pyrotinib (SHR1258), SCT200, CPGJ602, Sym004, MAb-425, Modotuximab (TAB-H49), futuximab (992 DS), zalutumumab, KL-140, RO5083945, IMGN289, JNJ-61186372, LY3164530, Sym013, AMG 595, BDTX-189, avatinib, Disruptin, CL-387785, EGFRBi-Armed Autologous T Cells, or EGFR CAR-T Therapy. In yet other aspects, the one or more additional therapeutic agent includes osimertinib (AZD9291, merelectinib, TAGRISSO®). In yet other aspects, the one or more additional therapeutic agent includes erlotinib (TARCEVA®). In yet other aspects, the one or more additional therapeutic agent includes gefitinib (IRESSA®). In yet other aspects, the one or more additional therapeutic agent includes cetuximab (ERBITUX®). In yet other aspects, the one or more additional therapeutic agent includes necitumumab (PORTRAZZA®, IMC-11F8). In yet other aspects, the one or more additional therapeutic agent includes neratinib (HKI-272, NERLYNX®). In yet other aspects, the one or more additional therapeutic agent includes lapatinib (TYKERB®). In yet other aspects, the one or more additional therapeutic agent includes panitumumab (ABX-EGF, VECTIBIX®). In yet other aspects, the one or more additional therapeutic agent includes vandetanib (CAPRELSA®). In yet other aspects, the one or more additional therapeutic agent includes rociletinib (CO-1686). In yet other aspects, the one or more additional therapeutic agent includes olmutinib (OLITA®, HM61713, BI-1482694). In yet other aspects, the one or more additional therapeutic agent includes naquotinib (ASP8273). In yet other aspects, the one or more additional therapeutic agent includes nazartinib (EGF816, NVS-816). In yet other aspects, the one or more additional therapeutic agent includes PF-06747775, icotinib (BPI-2009H). In yet other aspects, the one or more additional therapeutic agent includes afatinib (BIBW 2992, GILOTRIF®). In yet other aspects, the one or more additional therapeutic agent includes dacomitinib (PF-00299804, PF-804, PF-299, PF-299804). In yet other aspects, the one or more additional therapeutic agent includes avitinib (AC0010). In yet other aspects, the one or more additional therapeutic agent includes AC0010MA EAI045. In yet other aspects, the one or more additional therapeutic agent includes matuzumab (EMD-7200). In yet other aspects, the one or more additional therapeutic agent includes nimotuzumab (h-R3, BIOMAb EGFR®). In yet other aspects, the one or more additional therapeutic agent includes zalutumab. In yet other aspects, the one or more additional therapeutic agent includes MDX447. In yet other aspects, the one or more additional therapeutic agent includes depatuxizumab (humanized mAb 806, ABT-806). In yet other aspects, the one or more additional therapeutic agent includes depatuxizumab mafodotin (ABT-414). In yet other aspects, the one or more additional therapeutic agent includes ABT-806. In yet other aspects, the one or more additional therapeutic agent includes mAb 806. In yet other aspects, the one or more additional therapeutic agent includes canertinib (CI-1033). In yet other aspects, the one or more additional therapeutic agent includes shikonin. In yet other aspects, the one or more additional therapeutic agent includes one or more shikonin derivatives (e.g., deoxyshikonin, isobutyrylshikonin, acetylshikonin, β,β-dimethylacrylshikonin and acetylalkannin). In yet other aspects, the one or more additional therapeutic agent includes poziotinib (NOV120101, HM781-36B). In yet other aspects, the one or more additional therapeutic agent includes AV-412. In yet other aspects, the one or more additional therapeutic agent includes ibrutinib. In yet other aspects, the one or more additional therapeutic agent includes WZ4002. In yet other aspects, the one or more additional therapeutic agent includes brigatinib (AP26113, ALUNBRIG®). In yet other aspects, the one or more additional therapeutic agent includes pelitinib (EKB-569). In yet other aspects, the one or more additional therapeutic agent includes tarloxotinib (TH-4000, PR610). In yet other aspects, the one or more additional therapeutic agent includes BPI-15086. In yet other aspects, the one or more additional therapeutic agent includes Hemay022. In yet other aspects, the one or more additional therapeutic agent includes ZN-e4. In yet other aspects, the one or more additional therapeutic agent includes tesevatinib (KD019, XL647). In yet other aspects, the one or more additional therapeutic agent includes YH25448. In yet other aspects, the one or more additional therapeutic agent includes epitinib (HMPL-813). In yet other aspects, the one or more additional therapeutic agent includes CK-101. In yet other aspects, the one or more additional therapeutic agent includes MM-151. In yet other aspects, the one or more additional therapeutic agent includes AZD3759. In yet other aspects, the one or more additional therapeutic agent includes ZD6474. In yet other aspects, the one or more additional therapeutic agent includes PF-06459988. In yet other aspects, the one or more additional therapeutic agent includes varlintinib (ASLAN001, ARRY-334543). In yet other aspects, the one or more additional therapeutic agent includes AP32788. In yet other aspects, the one or more additional therapeutic agent includes HLX07. In yet other aspects, the one or more additional therapeutic agent includes D-0316. In yet other aspects, the one or more additional therapeutic agent includes AEE788. In yet other aspects, the one or more additional therapeutic agent includes HS-10296. In yet other aspects, the one or more additional therapeutic agent includes avitinib. In yet other aspects, the one or more additional therapeutic agent includes GW572016. In yet other aspects, the one or more additional therapeutic agent includes pyrotinib (SHR1258). In yet other aspects, the one or more additional therapeutic agent includes SCT200. In yet other aspects, the one or more additional therapeutic agent includes CPGJ602. In yet other aspects, the one or more additional therapeutic agent includes Sym004. In yet other aspects, the one or more additional therapeutic agent includes MAb-425. In yet other aspects, the one or more additional therapeutic agent includes Modotuximab (TAB-H49). In yet other aspects, the one or more additional therapeutic agent includes futuximab (992 DS). In yet other aspects, the one or more additional therapeutic agent includes zalutumumab. In yet other aspects, the one or more additional therapeutic agent includes KL-140. In yet other aspects, the one or more additional therapeutic agent includes RO5083945. In yet other aspects, the one or more additional therapeutic agent includes IMGN289. In yet other aspects, the one or more additional therapeutic agent includes JNJ-61186372. In yet other aspects, the one or more additional therapeutic agent includes LY3164530. In yet other aspects, the one or more additional therapeutic agent includes Sym013. In yet other aspects, the one or more additional therapeutic agent includes AMG 595. In yet other aspects, the one or more additional therapeutic agent includes BDTX-189. In yet other aspects, the one or more additional therapeutic agent includes avatinib. In yet other aspects, the one or more additional therapeutic agent includes Disruptin. In yet other aspects, the one or more additional therapeutic agent includes CL-387785. In yet other aspects, the one or more additional therapeutic agent includes EGFRBi-Armed Autologous T Cells. In yet other aspects, the one or more additional therapeutic agent includes EGFR CAR-T Therapy. [0326] Human Epidermal Growth Factor Receptor 2 (HER2 receptor) (also known as Neu, ErbB-2, CD340, or p185) inhibitors such as trastuzumab (e.g., TRAZIMERA™, HERCEPTIN®), pertuzumab (e.g., PERJETA®), trastuzumab emtansine (T-DM1 or ado-trastuzumab emtansine, e.g., KADCYLA®), lapatinib, KU004, neratinib (e.g., NERLYNX®), dacomitinib (e.g., VIZIMPRO®), afatinib (GILOTRIF®), tucatinib (e.g., TUKYSA™), erlotinib (e.g., TARCEVA®), pyrotinib, poziotinib, CP-724714, CUDC-101, sapitinib (AZD8931), tanespimycin (17-AAG), IPI-504, PF299, pelitinib, S-222611, and AEE-788. [0327] In some embodiments, the FGFR inhibitor is selected from infigratinib, AZD4547, erdafitinib (JNJ-42756493), nintedanib dovitinib, ponatinib, and TAS120. [0328] In some embodiments, the ALK inhibitor is selected from alectinib, crizotinib (XALKORI®), ceritinib, AP26113, ASP3026, TSR-011, PF-06463922, X-396, and CEP-37440. [0329] In some embodiments, the ROS1 inhibitor is selected from crizotinib (XALKORI®), ceritinib, lorlatinib, brigatinib, cabozantinib, and repotrectinib. [0330] In some embodiments, the mTOR inhibitor is selecte from everolimus, tacrolimus rapamycin, perifosine, and temsirolimus. [0331] In some embodiments, the Trk inhibitor is selected from larotrectinib, lestaurtinib, and entrectinib. [0332] In some embodiments, the RET inhibitors is selected from sunitinib (Sutent®), selpercatinib (RETEVMO®), vandetanib (Caprelsa®), motesanib (AMG706), sorafenib, regorafenib, and danusertib. [0333] In some embodiments, the MET inhibitor is selected from capmatinib, tepotinib, savolitinib, crizotinib, cabozantinib, tivantinib, bozitinib, merestinib, glesatinib, sitravatinib, onartuzumab, and emibetuzumab. [0334] In some embodiments, the AXL inhibitor is selected from sitravatinib, bemcentinib, dubermatinib, DS-1205, SLC-391, INCB081776, ONO-7475, and BA3011. [0335] In some embodiments, the Shp2 inhibitor is selected from TNO155, BBP-398, JAB-3068, RMC-4360, and RLY-1971. [0336] In some embodiments, the RAF inhibitor is a BRAF inhibitor, such as vemurafenib (ZELBORAF®), dabrafenib (TAFINLAR®), encorafenib (BRAFTOVI®), BMS-908662, sorafenib, LGX818, PLX3603, RAF265, RO5185426, GSK2118436, ARQ 736, GDC-0879, PLX-4720, AZ304, PLX-8394, HM95573, RO5126766, and LXH254. [0337] In some embodiments, the PI3K inhibitor is selected from buparlisib (BKM120), alpelisib (BYL719), WX-037, copanlisib (ALIQOPA®, BAY80-6946), dactolisib (NVP-BEZ235, BEZ-235), taselisib (GDC-0032, RG7604), sonolisib (PX-866), CUDC-907, PQR309, ZSTK474, SF1126, AZD8835, GDC-0077, ASN003, pictilisib (GDC-0941), pilaralisib (XL147, SAR245408), gedatolisib (PF-05212384, PKI-587), serabelisib (TAK-117, MLN1117, INK 1117), BGT-226 (NVP-BGT226), PF-04691502, apitolisib (GDC-0980), omipalisib (GSK2126458, GSK458), voxtalisib (XL756, SAR245409), AMG 511, CH5132799, GSK1059615, GDC-0084 (RG7666), VS-5584 (SB2343), PKI-402, wortmannin, LY294002, PI-103, rigosertib, XL-765, LY2023414, SAR260301, KIN-193 (AZD-6428), GS-9820, AMG319, and GSK2636771. [0338] In some embodiments, the AKT inhibitor is selected from miltefosine (IMPADIVO®), wortmannin, NL-71-101, H-89, GSK690693, CCT128930, AZD5363, ipatasertib (GDC-0068, RG7440), A-674563, A-443654, AT7867, AT13148, uprosertib, afuresertib, DC120, MK-2206, edelfosine, miltefosine, perifosine, erucylphophocholine, erufosine, SR13668, OSU-A9, PH-316, PHT-427, PIT-1, DM-PIT-1, triciribine, API-1, ARQ092, BAY 1125976, 3-oxo-tirucallic acid, lactoquinomycin, GSK2141795, ONC201, tricirbine, A674563, and AT7867. [0339] In some embodiments, the MEK inhibitor is selected from trametinib (MEKINIST®), cobimetinib (COTELLIC®), binimetinib (MEKTOVI®), selumetinib (AZD6244), PD0325901, MSC1936369B, SHR7390, TAK-733, RO5126766, CS3006, WX-554, PD98059, CI1040 (PD184352), and hypothemycin. [0340] In some embodiments, the ERK inhibitor is selected from FRI-20 (ON-01060), VTX-11e, 25-OH-D3-3-BE (B3CD, bromoacetoxycalcidiol), FR-180204, AEZ-131 (AEZS-131), AEZS-136, AZ-13767370, BL-EI-001, LY-3214996, LTT-462, KO-947, MK-8353 (SCH900353), SCH772984, ulixertinib (BVD-523), CC-90003, GDC-0994 (RG-7482), ASN007, FR148083, 5-7-Oxozeaenol, 5-iodotubercidin, GDC0994, and ONC201. [0341] In some embodiments, the PARP inhibitors include olaparib (LYNPARZA®), talazoparib, rucaparib, niraparib, veliparib, BGB-290 (pamiparib), CEP 9722, E7016, iniparib, IMP4297, NOV1401, 2X-121, ABT-767, RBN-2397, BMN 673, KU-0059436 (AZD2281), BSI-201, PF-01367338, INO-1001, and JPI-289. [0342] In some embodiments, the RAS inhibitor is MRTX849, LY3499446, JNJ-74699157, AMG 510, ARS3248, ARS853, ARS1620, AZD4785, JNJ-74699157, SML-8-73-1, SML-10-70-1, VSA9, AA12, and MRTX-849. [0343] In some embodiments, the PDK-1 inhibitor is selected from GSK 2334470, JX06, SNS-510, and AR-12. [0344] In some embodiments, the BET inhibitor is selected from GSK1210151A, GSK525762, OTX-015, TEN-010, CPI-203, CPI-0610, olinone, RVX-208, ABBV-744, LY294002, AZD5153, MT-1, and MS645. [0345] In some embodiments, the MCL-1 inhibitor is AZD5991. [0346] In some embodiments, the Bcl-2 protein family inhibitor is selected from ABT-263, Tetrocarcin A, Antimycin, Gossypol ((−)BL-193), obatoclax, HA14-1, oblimersen (Genasense®); (−)-Gossypol acetic acid (AT-101); ABT-737, and navitoclax. [0347] In some embodiments, the Bcr/Abl kinase inhibitor is selected from imatinib (Gleevec®), inilotinib, nilotinib (Tasigna®), dasatinib (BMS-345825), bosutinib (SKI-606), ponatinib (AP24534), bafetinib (INNO406), danusertib (PHA-739358), AT9283, saracatinib (AZD0530), and PF-03814735. [0348] In some embodiments, the checkpoint inhibitor is selected from ipilimumab (YERVOY®), pembrolizumab (KEYTRUDA®), nivolumab (OPDIVO®), cemiplimab (LIBTAYO®), atezolizumab (TECENTRIQ®), avelumab (BAVENCIO®), durvalumab (IMFINZI®), IMP701 (LAG525), CPI-444, MBG453, enoblituzumab, JNJ-61610588, and indoximod. See, e.g., Marin-Acevedo, et. al., J Hematol Oncol.11: 39 (2018). [0349] In some embodiments, the other immunotherapy is an antibody therapy (e.g., a monoclonal antibody). In some embodiments, the antibody therapy is selected from bevacizumab (Mvasti™, Avastin®), trastuzumab (Herceptin®), rituximab (MabThera™, Rituxan®), edrecolomab (Panorex), daratumuab (Darzalex®), olaratumab (Lartruvo™), ofatumumab (Arzerra®), alemtuzumab (Campath®), cetuximab (Erbitux®), oregovomab, dinutiximab (Unituxin®), obinutuzumab (Gazyva®), tremelimumab (CP-675,206), ramucirumab (Cyramza®), ublituximab (TG-1101), panitumumab (Vectibix®), elotuzumab (Empliciti™), necitumumab (Portrazza™), cirmtuzumab (UC-961), ibritumomab (Zevalin®), isatuximab (SAR650984), nimotuzumab, fresolimumab (GC1008), lirilumab (INN), mogamulizumab (Poteligeo®), ficlatuzumab (AV-299), denosumab (Xgeva®), ganitumab, urelumab, pidilizumab, and amatuximab. [0350] In some embodiments, the other chemotherapeutic agents are selected from an anthracycline, an alkylating agent, a taxane, a platinum-based agent, eribulin (HALAVEN^TM), a farnesyl transferase inhibitor, a topoisomerase inhibitor, a DNA synthesis inhibitor, and cytotoxic agents. [0351] In some embodiments, the taxane is selected from paclitaxel, docetaxel, cabazitaxel, abraxane, and taxotere. [0352] In some embodiments, the anthracycline is selected from daunorubicin, doxorubicin, epirubicin, idarubicin, and combinations thereof. [0353] In some embodiments, the platinum-based agent is selected from carboplatin, cisplatin, oxaliplatin, nedplatin, triplatin tetranitrate, phenanthriplatin, picoplatin, and satraplatin. [0354] In some embodiments, the farnesyl transferase inhibitor is selected from lonafarnib, tipifarnib, BMS-214662, L778123, L744832, and FTI-277. [0355] In some embodiments, the topoisomerase inhibitor is a topoisomerase I inhibitor (e.g., irinotecan (Camptosar®), topotecan (Hycamtin®), and 7-Ethyl-10-hydroxycampothecin (SN38)) or a topoisomerase II inhibitor (e.g., etoposide (Toposar®, VePesid®, and Etopophos®), teniposide (VM-26, Vumon®), and tafluposide. [0356] In some embodiments, the DNA synthesis inhibitor is selected from capecitabine (Xeloda®), gemcitabine hydrochloride (Gemzar®), nelarabine (Arranon® and Atriance®), and sapacitabine. [0357] In some embodiments, the alkylating agent is selected from temozolomide (Temodar® and Temodal®), dactinomycin (also known as actinomycin-D, Cosmegen®), melphalan (Alkeran®), altretamine (Hexalen®), carmustine (BiCNU®), bendamustine (Treanda®), busulfan (Busulfex® and Myleran®), lomustine (CeeNU®), chlorambucil (Leukeran®), cyclophosphamide (Cytoxan® and Neosar®), dacarbazine (DTIC-Dome®), altretamine (Hexalen®), ifosfamide (Ifex®), prednumustine, procarbazine (Matulane®), mechlorethamine (Mustargen®), streptozocin (Zanosar®), and thiotepa (Thioplex®). [0358] In some embodiments, the cytotoxic agent is selected from bleomycin, cytarabine, dacarbazine, methotrexate, mitomycin C, pemetrexed, and vincristine. [0359] In any case, the multiple therapeutic agents (at least one of which is a compound of the various embodiments disclosed herein) may be administered in any order or even simultaneously. If simultaneously, the multiple therapeutic agents may be provided in a single, unified form, or in multiple forms (by way of example only, either as a single pill or as two separate pills). One of the therapeutic agents may be given in multiple doses, or both may be given as multiple doses. If not simultaneous, the timing between the multiple doses may be any duration of time ranging from a few minutes to four weeks. [0360] Also provided herein is (i) a pharmaceutical combination for treating a cancer in a subject in need thereof, which includes (a) a compound of the invention, or a pharmaceutically acceptable salt thereof, (b) at least one additional therapeutic agent (e.g., any of the exemplary additional therapeutic agents described herein or known in the art), and (c) optionally at least one pharmaceutically acceptable carrier for simultaneous, separate or sequential use for the treatment of cancer, wherein the amounts of the compound of the invention, or pharmaceutically acceptable salt thereof, and of the additional therapeutic agent are together effective in treating the cancer; (ii) a pharmaceutical composition including such a combination; (iii) the use of such a combination for the preparation of a medicament for the treatment of cancer; and (iv) a commercial package or product including such a combination as a combined preparation for simultaneous, separate or sequential use; and to a method of treatment of cancer in a subject in need thereof. In some embodiments, the cancer is an EGFR pathway-associated cancer. [0361] The term “pharmaceutical combination”, as used herein, refers to a pharmaceutical therapy resulting from the mixing or combining of more than one active ingredient and includes both fixed and non-fixed combinations of the active ingredients. The term “fixed combination” means that a compound of the invention, or a pharmaceutically acceptable salt thereof, and at least one additional therapeutic agent (e.g., a chemotherapeutic agent), are both administered to a subject simultaneously in the form of a single composition or dosage. The term “non-fixed combination” means that a compound of the invention, or a pharmaceutically acceptable salt thereof, and at least one additional therapeutic agent (e.g., chemotherapeutic agent) are formulated as separate compositions or dosages such that they may be administered to a subject in need thereof simultaneously, concurrently or sequentially with variable intervening time limits, wherein such administration provides effective levels of the two or more compounds in the body of the subject. These also apply to cocktail therapies, e.g., the administration of three or more active ingredients. C. Dosage [0362] The compositions including a compound of the invention or a pharmaceutically acceptable salt thereof can be formulated in a unit dosage form, each dosage containing from about 5 to about 1,000 mg (1 g), more usually about 100 mg to about 500 mg, of the active ingredient. The term “unit dosage form” refers to physically discrete units suitable as unitary dosages for human subjects and other subjects, each unit containing a predetermined quantity of active material (i.e., a compound of the invention or a pharmaceutically acceptable salt thereof) calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient. [0363] In some embodiments, the compositions provided herein contain from about 5 mg to about 50 mg of the active ingredient. [0364] In some embodiments, the compositions provided herein contain from about 50 mg to about 500 mg of the active ingredient. In some embodiments, the compositions provided herein contain about 10 mg, about 20 mg, about 80 mg, or about 160 mg of the active ingredient. [0365] In some embodiments, the compositions provided herein contain from about 500 mg to about 1,000 mg of the active ingredient. [0366] The daily dosage of the compound of the invention or a pharmaceutically acceptable salt thereof can be varied over a wide range from 1.0 to 10,000 mg per adult human per day, or higher, or any range therein. For oral administration, the compositions are preferably provided in the form of tablets containing, 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 15.0, 25.0, 50.0, 100, 150, 160, 200, 250 and 500 milligrams of the active ingredient for the symptomatic adjustment of the dosage to the subject to be treated. An effective amount of the drug is ordinarily supplied at a dosage level of from about 0.1 mg/kg to about 1000 mg/kg of body weight per day, or any range therein. Preferably, the range is from about 0.5 to about 500 mg/kg of body weight per day, or any range therein. In an example, the range can be from about 0.1 to about 50.0 mg/kg of body weight per day, or any amount or range therein. In another example, the range can be from about 0.1 to about 15.0 mg/kg of body weight per day, or any range therein. In yet another example, the range can be from about 0.5 to about 7.5 mg/kg of body weight per day, or any amount to range therein. Pharmaceutical compositions containing a compound of the invention or a pharmaceutically acceptable salt thereof can be administered on a regimen of 1 to 4 times per day or in a single daily dose. [0367] The active compound may be effective over a wide dosage range and is generally administered in a pharmaceutically effective amount. Optimal dosages to be administered can be readily determined by those skilled in the art. It will be understood, therefore, that the amount of the compound actually administered will usually be determined by a physician, and will vary according to the relevant circumstances, including the mode of administration, the actual compound administered, the strength of the preparation, the condition to be treated, and the advancement of the disease condition. In addition, factors associated with the particular subject being treated, including subject response, age, weight, diet, time of administration and severity of the subject’s symptoms, will result in the need to adjust dosages. [0368] In some embodiments, the compounds provided herein can be administered in an amount ranging from about 1 mg/kg to about 100 mg/kg. In some embodiments, the compound provided herein can be administered in an amount of about 1 mg/kg to about 20 mg/kg, about 5 mg/kg to about 50 mg/kg, about 10 mg/kg to about 40 mg/kg, about 15 mg/kg to about 45 mg/kg, about 20 mg/kg to about 60 mg/kg, or about 40 mg/kg to about 70 mg/kg. In some embodiments, such administration can be once-daily or twice-daily (BID) administration. [0369] One skilled in the art will recognize that both in vivo and in vitro trials using suitable, known and generally accepted cell and/or animal models are predictive of the ability of a test compound to treat or prevent a given disorder. [0370] One skilled in the art will further recognize that human clinical trials including first-in-human, dose ranging and efficacy trials, in healthy subjects and/or those suffering from a given disorder, can be completed according to methods well known in the clinical and medical arts. [0371] Provided herein are pharmaceutical kits useful, for example, in the treatment of EGFR pathway-associated diseases or disorders, such as cancer, which include one or more containers containing a pharmaceutical composition including an effective amount of a compound provided herein. Such kits can further include, if desired, one or more of various conventional pharmaceutical kit components, such as, for example, containers with one or more pharmaceutically acceptable carriers, additional containers, etc., as will be readily apparent to those skilled in the art. Instructions, either as inserts or as labels, indicating quantities of the components to be administered, guidelines for administration, and/or guidelines for mixing the components, can also be included in the kit. V. USES OF COMPOUNDS, PHARMACEUTICALLY ACCEPTABLE SALTS, AND PHARMACEUTICAL COMPOSITIONS OF THE INVENTION A. Methods of Treatment Using Compounds, Pharmaceutically Acceptable Salts, and Compositions of the Invention [0372] Provided herein is a method of treating cancer (e.g., an EGFR-associated cancer) in a subject in need of such treatment. The method includes administering to the subject an effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof. In some embodiments, a cancer is an EGFR-associated cancer. In some embodiments, a cancer is associated with a dysregulation of an EGFR pathway gene, an EGFR pathway protein, or expression or activity or level of any of the same. [0373] For example, provided herein are methods for treating an EGFR pathway-associated cancer (e.g., an EGFR-associated cancer), a RAS-associated cancer, an ErbB2-associated cancer, an ErbB3-associated cancer, an ErbB4-associated cancer, a NF1-associated cancer, a PDGFR-A-associated cancer, a PDGFR-B-associated cancer, a FGFR1-associated cancer, FGFR2-associated cancer, FGFR3-associated cancer, a IGF1 R-associated cancer, a INSR-associated cancer, a ALK-associated cancer, a ROS-associated cancer, a TrkA-associated cancer, a TrkB-associated cancer, a TrkC-associated cancer, a RET-associated cancer, a c-MET-associated cancer, a VEGFR1-associated cancer, a VEGFR2-associated cancer, a VEGFR3-associated cancer, an AXL-associated cancer, a SHP2-associated cancer, a RAF-associated cancer (e.g., a BRAF-associated cancer), a PI3K-associated cancer, an AKT-associated cancer, an mTOR-associated cancer, a MEK-associated cancer, an ERK-associated cancer, or a combination thereof) in a subject in need of such treatment. The method includes a) detecting a dysregulation of an EGFR pathway gene, an EGFR pathway protein, or the expression or activity or level of any of the same in a sample from the subject; and b) administering an effective amount of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof. [0374] In some aspects, embodiments herein relate to methods of treating a subject with cancer (e.g., a cancer associated with a dysregulation of an EGFR gene, an EGFR protein, or the expression or activity or level of any of the same) including administering to the subject a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. [0375] For example, provided herein is a method of treating an EGFR-associated cancer in a subject in need of such treatment, including administering to the subject an effective amount of a compound of of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. [0376] The term “EGFR-associated cancer” as used herein refers to cancers associated with or having a dysregulation of an EGFR gene, an EGFR protein, or the expression or activity or level of any (e.g., one or more) of the same (e.g., any of the types of dysregulation of an EGFR gene, an EGFR protein, or the expression or activity or level of any of the same, as described herein). Examples of an EGFR-associated cancer include, but are not limited to cancers of the head and neck, breast, colon, prostate, lung (e.g., NSCLC, adenocarcinoma and squamous lung cancer), ovaries, gastrointestinal cancers (gastric, colon, pancreatic), renal cell cancer, bladder cancer, glioma, glioblastoma, gynecological carcinomas, and prostate cancer. [0377] The phrase “dysregulation of an EGFR gene, an EGFR protein, or the expression or activity or level of any of the same” refers to a genetic mutation that results in the expression of a mutation in an EGFR gene that results in the expression of an EGFR protein that includes a deletion of at least one amino acid as compared to a wild type EGFR protein, a mutation in an EGFR gene that results in the expression of an EGFR protein with one or more point mutations as compared to a wild type EGFR protein, a mutation in an EGFR gene that results in the expression of an EGFR protein with at least one inserted amino acid as compared to a wild type EGFR protein, a gene duplication that results in an increased level of EGFR protein in a cell, or a mutation in a regulatory sequence (e.g., a promoter and/or enhancer) that results in an increased level of EGFR protein in a cell), an alternative spliced version of an EGFR mRNA (e.g., that results in an EGFR protein having a deletion of at least one amino acid in the EGFR protein as compared to the wild type EGFR protein or that results in an EGFR protein having an insertion of at least one amino acid in the EGFR protein as compared to the wild type EGFR protein), or increased expression (e.g., increased levels) of a wild type EGFR protein in a mammalian cell due to aberrant cell signaling and/or dysregulated autocrine/paracrine signaling (e.g., as compared to a control non-cancerous cell). [0378] In some embodiments, the subject has been identified or diagnosed as having an EGFR-associated cancer. As such, provided herein is a method for treating cancer in a subject in need thereof, including: (a) determining that the cancer is associated with a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same; and (b) administering to the subject an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. [0379] For example, provided herein are methods for treating an EGFR-associated cancer in a subject in need of such treatment. The method includes a) detecting a dysregulation of an EGFR gene, an EGFR protein, or the expression or activity or level of any of the same in a sample from the subject; and b) administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. [0380] Also provided are methods for treating cancer in a subject in need thereof, the method includes: (a) detecting an EGFR-associated cancer in the subject; and (b) administering to the subject an effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. Some embodiments of these methods further include administering to the subject another anticancer agent (e.g., a small molecule or an immunotherapy). In some embodiments, the subject was previously treated with another anticancer treatment, e.g., at least partial resection of the tumor or radiation therapy. In some embodiments, the subject is determined to have an EGFR-associated cancer through the use of a regulatory agency-approved, e.g., FDA-approved test or assay for identifying a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, in a subject or a biopsy sample from the subject or by performing any of the non-limiting examples of assays described herein. In some embodiments, the test or assay is provided as a kit. [0381] EGFR is a transmembrane protein tyrosine kinase of the ErbB receptor family. When bound to a growth factor ligand (e.g., epidermal growth factor (EGF)), the receptor can homodimerize with an additional EGFR molecule, or it may heterodimerize with another family member (e.g., ErbB2 (HER2), ErbB3 (HER3), or ErbB4 (HER4)). Homologous dimerization and/or heterodimerization of the ErbB receptor results in phosphorylation of key tyrosine residues in the intracellular domain and results in stimulation of many intracellular signaling pathways involved in cell proliferation and survival. [0382] EGFR inhibitors are capable of decreasing both the mitogen-activated protein kinase (MAPK) and PI3K/AKT protein kinase pathways (Phuchareon et al., Proc Natl Acad Sci USA 112(29):E3855-63 (2015)). The MAPK pathway is involved in the regulation of cell growth, survival, and differentiation, and elevated level of MAPK expression have been detected in a variety of human tumors and may be associated with invasive, metastatic and angiogenic activities of tumor cells. (Hoshino, R. et al., Oncogene 18:813-822 (1999); Salh, B et al., Anticancer Res.19:741-48 (1999); Sivaraman, V S et al., J. Clin. Invest.99:1478-483 (1997); Mandell, J W et al., Am. J. Pathol.153: 1411-23 (1998); Licato, L. L. et al. Digestive Diseases and Sciences 43, 1454-1464 (1998)). The phoshatidylinositol 3-kinase (Pi3K)/Akt protein kinase pathway is thought to be central to the control of cell growth, proliferation, and survival, driving progression of tumors. In some embodiments, the EGFR pathway-associated cancer is a MAPK-associated cancer, a Pi3K associated cancer and/or an AKT-associated cancer. [0383] Also provided herein is a method of treating an EGFR pathway-associated disease or disorder in a subject in need of such treatment, including administering to the subject an effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as defined herein. In some embodiments, the EGFR pathway-associated disease or disorder is an EGFR-associated cancer. In some embodiments, the EGFR pathway-associated cancer is a MAPK-associated cancer, a Pi3K associated cancer and/or an AKT-associated cancer. In accordance with this aspect, also provided herein is a compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as defined herein for use in the treatment of an EGFR pathway-associated disease or disorder (e.g., an EGFR-associated cancer). [0384] Also provided are methods for treating cancer in a subject in need thereof, the method includes: administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to the subject. In some embodiments, the subject is determined to have a cancer associated with a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same. Some embodiments of these methods further include administering to the subject another anticancer agent (e.g., a small molecule or an immunotherapy). In some embodiments, the subject was previously treated with another anticancer treatment, e.g., at least partial resection of the tumor or radiation therapy. In some embodiments, the subject is determined to have an EGFR-associated cancer through the use of a regulatory agency-approved, e.g., FDA-approved test or assay for identifying dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, in a subject or a biopsy sample from the subject or by performing any of the non-limiting examples of assays described herein. In some embodiments, the test or assay is provided as a kit. [0385] Also provided are methods of treating a subject that include performing an assay on a sample obtained from the subject to determine whether the subject has a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, and administering (e.g., specifically or selectively administering) an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, to the subject determined to have a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same. Some embodiments of these methods further include administering to the subject another anticancer agent (e.g., a small molecule or immunotherapy). In some embodiments of these methods, the subject was previously treated with another anticancer treatment, e.g., at least partial resection of a tumor or radiation therapy. In some embodiments, the subject is a subject suspected of having an EGFR-associated cancer, a subject presenting with one or more symptoms of an EGFR-associated cancer, or a subject having an elevated risk of developing an EGFR-associated cancer. In some embodiments, the assay utilizes next generation sequencing, pyrosequencing, immunohistochemistry, or break apart FISH analysis. In some embodiments, the assay is a regulatory agency-approved assay, e.g., FDA-approved kit. In some embodiments, the assay is a liquid biopsy. Additional, non-limiting assays that may be used in these methods are described herein. Additional assays are also known in the art. [0386] Also provided is a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in treating an EGFR-associated cancer in a subject identified or diagnosed as having an EGFR-associated cancer through a step of performing an assay (e.g., an in vitro assay) on a sample obtained from the subject to determine whether the subject has a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, where the presence of a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, identifies that the subject has an EGFR-associated cancer. Also provided is the use of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating an EGFR-associated cancer in a subject identified or diagnosed as having an EGFR-associated cancer through a step of performing an assay on a sample obtained from the subject to determine whether the subject has a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same where the presence of dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, identifies that the subject has an EGFR-associated cancer. Some embodiments of any of the methods or uses described herein further include recording in the subject’s clinical record (e.g., a computer readable medium) that the subject is determined to have a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, through the performance of the assay, should be administered a compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the assay utilizes next generation sequencing, pyrosequencing, immunohistochemistry, or break apart FISH analysis. In some embodiments, the assay is a regulatory agency-approved assay, e.g., FDA-approved kit. In some embodiments, the assay is a liquid biopsy. [0387] In some embodiments of any of the methods or uses described herein, the subject has been identified or diagnosed as having a cancer with a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same. In some embodiments of any of the methods or uses described herein, the subject has a tumor that is positive for a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same. In some embodiments of any of the methods or uses described herein, the subject can be a subject with a tumor(s) that is positive for a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same. In some embodiments of any of the methods or uses described herein, the subject can be a subject whose tumors have a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same. In some embodiments of any of the methods or uses described herein, the subject is suspected of having an EGFR-associated cancer. In some embodiments, provided herein are methods for treating an EGFR-associated cancer in a subject in need of such treatment. The method includes a) detecting a dysregulation of an EGFR gene, an EGFR protein, or the expression or activity or level of any of the same in a sample from the subject; and b) administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the dysregulation of an EGFR gene, an EGFR protein, or the expression or activity or level of any of the same includes one or more EGFR protein point mutations/insertions/deletions. [0388] In some embodiments, the cancer with a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same is determined using a regulatory agency-approved, e.g., FDA-approved, assay or kit. In some embodiments, the tumor with a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same is determined using a regulatory agency-approved, e.g., FDA-approved, assay or kit. [0389] In some embodiments of any of the methods or uses described herein, the subject has a clinical record indicating that the subject has a tumor that has a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same. Also provided are methods of treating a subject that include administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, to a subject having a clinical record that indicates that the subject has a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same. [0390] In some embodiments, the methods provided herein include performing an assay on a sample obtained from the subject to determine whether the subject has a dysregulation of an EGFR gene, an EGFR protein, or expression or level of any of the same. In some such embodiments, the method also includes administering to a subject determined to have a dysregulation of an EGFR gene, an EGFR protein, or expression or activity, or level of any of the same an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the method includes determining that a subject has a dysregulation of an EGFR gene, an EGFR protein, or expression or level of any of the same via an assay performed on a sample obtained from the subject. In such embodiments, the method also includes administering to a subject an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. [0391] In some embodiments of any of the methods or uses described herein, the cancer is a solid tumor (e.g., solid tumors that are EGFR-associated cancers). Examples of solid tumors include, but are not limited to, thyroid cancer (e.g., papillary thyroid carcinoma, medullary thyroid carcinoma), lung cancer (e.g., non-small cell lung cancer, small-cell lung carcinoma, bronchial adenoma, and pleuropulmonary blastoma), pancreatic cancer, pancreatic ductal carcinoma, biliary tract cancer, breast cancer (e.g., invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, and lobular carcinoma in situ), stomach cancer, small intestinal cancer, colon cancer, colorectal cancer, peritoneal cancer, ovarian cancer, uterine cancer, liver cancer, endometrial cancer, prostate cancer (including benign prostatic hyperplasia), testicular cancer, bladder cancer, urinary tract cancer, cervical cancer, head and neck cancer, brain cancer (e.g., glioblastoma, brain stem and hypophtalmic glioma, cerebellar and cerebral astrocytoma, medulloblastoma, and ependymoma), squamous cell carcinoma, and melanoma. In other embodiments, the cancer is thyroid cancer. In other embodiments, the cancer is papillary thyroid carcinoma. In other embodiments, the cancer is medullary thyroid carcinoma. In other embodiments, the cancer is lung cancer. In other embodiments, the cancer is non-small cell lung cancer. In other embodiments, the cancer is EGFR-associated non-small cell lung cancer. In other embodiments, the cancer is EGFR-mutated non-small cell lung cancer. In other embodiments, the cancer is small-cell lung carcinoma. In other embodiments, the cancer is bronchial adenoma. In other embodiments, the cancer is pleuropulmonary blastoma. In other embodiments, the cancer is pancreatic cancer. In other embodiments, the cancer is pancreatic ductal carcinoma. In other embodiments, the cancer is biliary tract cancer. In other embodiments, the cancer is breast cancer. In other embodiments, the cancer is invasive ductal carcinoma. In other embodiments, the cancer is invasive lobular carcinoma. In other embodiments, the cancer is ductal carcinoma in situ. In other embodiments, the cancer is and lobular carcinoma in situ. In other embodiments, the cancer is stomach cancer. In other embodiments, the cancer is small intestinal cancer. In other embodiments, the cancer is colon cancer. In other embodiments, the cancer is colorectal cancer. In other embodiments, the cancer is peritoneal cancer. In other embodiments, the cancer is ovarian cancer. In other embodiments, the cancer is uterine cancer. In other embodiments, the cancer is liver cancer. In other embodiments, the cancer is endometrial cancer. In other embodiments, the cancer is prostate cancer. In other embodiments, the cancer is benign prostatic hyperplasia. In other embodiments, the cancer is testicular cancer. In other embodiments, the cancer is bladder cancer. In other embodiments, the cancer is urinary tract cancer. In other embodiments, the cancer is cervical cancer. In other embodiments, the cancer is head and neck cancer. In other embodiments, the cancer is brain cancer. In other embodiments, the cancer is glioblastoma. In other embodiments, the cancer is brain stem and hypophtalmic glioma. In other embodiments, the cancer is cerebellar and cerebral astrocytoma. In other embodiments, the cancer is medulloblastoma. In other embodiments, the cancer is ependymoma. In other embodiments, the cancer is squamous cell carcinoma. In other embodiments, the cancer is melanoma. [0392] In some embodiments, the invention relates to a method of treating non-small cell lung cancer in a subject in need thereof, the method including administering to the subject an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the invention relates to a method of treating EGFR-associated non-small cell lung cancer in a subject in need thereof, the method including administering to the subject an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the invention relates to a method of treating EGFR-mutated non-small cell lung cancer in a subject in need thereof, the method including administering to the subject an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. [0393] In some embodiments, the invention relates to a method of treating non-small cell lung cancer in a subject, the method including administering to the subject a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the invention relates to a method of treating EGFR-associated non-small cell lung cancer in a subject, the method including administering to the subject a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the invention relates to a method of treating EGFR-mutated non-small cell lung cancer in a subject, the method including administering to the subject an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. [0394] In some embodiments, the subject is a human. [0395] Compounds of Formula (I) and pharmaceutically acceptable salts and solvates thereof are also useful for treating an EGFR-associated cancer. As such, also provided herein is a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as defined herein for use in the treatment of cancer. [0396] Accordingly, also provided herein is a method for treating a subject diagnosed with or identified as having an EGFR-associated cancer, e.g., any of the exemplary EGFR-associated cancers disclosed herein, including administering to the subject an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the compound of the invention is selected from Examples 1-77, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. [0397] Dysregulation of an EGFR pathway protein, an EGFR pathway gene, or the expression or activity or level of any (e.g., one or more) of the same can contribute to tumorigenesis. For example, a specific deletion-mutation in the EGFR gene (EGFRvIII) has been found to increase cellular tumorigenicity as compared to a wild type EGFR gene. Activation of EGFR stimulated signaling pathways promote multiple processes that are potentially cancer-promoting, e.g., proliferation, angiogenesis, cell motility and invasion, decreased apoptosis and induction of drug resistance. Increased EGFR expression is frequently linked to advanced disease, metastases, and poor prognosis. For example, in NSCLC and gastric cancer, increased EGFR expression has been shown to correlate with a high metastatic rate, poor tumor differentiation, and increased tumor proliferation. [0398] Cancers associated with mutations of the EGFR gene and/or protein are often associated with poor prognosis. Lung cancer patients harboring EGFR mutations frequently develop progressive cancer while receiving therapy. A secondary EGFR mutation, T790M, can render some EGFR inhibitors ineffective. The EGFR T790M mutation is found in approximately 50% of tumors from patients that acquire resistance to gefitinib or erlotinib. This secondary genetic alteration occurs in the “gatekeeper” residue and in an analogous position to other secondary resistance alleles in diseases treated with kinase inhibitors, e.g., T315I in ABL in imatinib resistant chronic myeloid leukemia (CML). [0399] The predominant oncogenic EGFR mutations (L858R and ex19del) account for about 90% of EGFR NSCLC. Besides the classic EGFR mutations (L858R and Ex19Del), EGFR Exon 20 insertion mutations (Ex20ins) were described to account for 4-10% of all EGFR mutations in patients, the third largest EGFR mutant patient population behind the classic (L858R and ex19del) EGFR mutations. Somatic mutations in lung cancer identified to date include point mutations in which a single amino acid residue is altered in the expressed protein (e.g. L858R, G719S, G719C, G719A, L861Q), as well as small in frame deletions in exon 19 or insertions in exon 20. [0400] In some embodiments, the EGFR-associated cancer is linked to an EGFR mutation, including, but not limited to L858R, C797S, E746-A750 deletions, T790M, G719S, G719C, G719A, L861Q, and any combination thereof. [0401] In some embodiments, of any of the methods or uses described herein, the EGFR gene and/or protein has developed a resistance to inhibition with a previous tyrosine kinase inhibitor (e.g., gefitinib, erlotinib, and/or lapatinib). [0402] In some embodiments, the compounds provided herein are selective EGFR inhibitors. As used herein, the term “selective EGFR inhibitor” means a compound that selectively inhibits certain mutant EGFR kinases over wild-type EGFR and the kinome. Said another way, a selective EGFR inhibitor has no or low activity against wild-type EGFR and the kinome. A selective EGFR inhibitor’s inhibitory activity against certain mutant EGFR kinases is more potent in terms of IC₅₀ value (i.e., a nanomolar IC₅₀ value) when compared with its inhibitory activity against wild-type EGFR and many other kinases. Potency can be measured using known biochemical assays. [0403] In some embodiments, the compounds provided herein exhibit brain and/or central nervous system (CNS) penetrance. Such compounds are capable of crossing the blood brain barrier and inhibiting the EGFR pathway (e.g., EGFR, MAPK, and/or AKT or a combination thereof) activity in the brain and/or other CNS structures. In some embodiments, the compounds provided herein are capable of crossing the blood brain barrier in an effective amount. For example, treatment of a subject with cancer (e.g., an EGFR pathway-associated cancer such as an EGFR-associated brain or CNS cancer) can include administration (e.g., oral administration) of the compound of the invention to the subject. In some such embodiments, the compounds provided herein are useful for treating a primary brain tumor or metastatic brain tumor. For example, the compounds can be used in the treatment of one or more of gliomas such as glioblastoma (also known as glioblastoma multiforme), astrocytomas, oligodendrogliomas, ependymomas, and mixed gliomas, meningiomas, medulloblastomas, gangliogliomas, schwannomas (neurilemmomas), and craniopharyngiomas (see, for example, the tumors listed in Louis, D.N. et al., Acta Neuropathol 131(6), 803-820 (June 2016)). In some embodiments, the brain tumor is a primary brain tumor. In some embodiments, the subject has previously been treated with another anticancer agent, e.g., another EGFR pathway inhibitor (e.g., a compound that is not a compound of the invention), or an inhibitor of another tumorgenic pathway gene or protein (e.g., Ras (e.g., KRas, HRas, and/or NRas), ErbB2, ErbB3, ErbB4, NF1, PDGFR-A, PDGFR-B, FGFR1, FGFR2, FGFR3, IGF1 R, INSR, ALK, ROS, TrkA, TrkB, TrkC, RET, c-MET, VEGFR1, VEGFR2, VEGFR3, AXL, SHP2, RAF (e.g., BRAF), PI3K, AKT, mTOR, MEK, ERK, or a combination thereof). In some embodiments, the brain tumor is a metastatic brain tumor. [0404] The ability of the compounds described herein, to cross the BBB can be demonstrated by assays known in the art. Such assays include BBB models such as the transwell system, the hollow fiber (dynamic in vitro BBB) model, other microfluidic BBB systems, the BBB spheroid platform, and other cell aggregate-based BBB models. See, e.g., Cho et al. Nat Commun. 2017; 8: 15623; Bagchi, et al. Drug Des Devel Ther. 2019; 13: 3591–3605; Gastfriend, et al. Curr Opin Biomed Eng. 2018 Mar; 5: 6–12; and Wang et al. Biotechnol Bioeng. 2017 Jan; 114(1): 184–194. In some embodiments, the compounds described herein, are fluorescently labeled, and the fluorescent label can be detected using microscopy (e.g., confocal microscopy). In some such embodiments, the ability of the compound to penetrate the surface barrier of the model can be represented by the fluorescence intensity at a given depth below the surface. In some assays, such as a calcein-AM-based assay, the fluorescent label is non-fluorescent until it permeates live cells and is hydrolyzed by intracellular esterases to produce a fluorescent compound that is retained in the cell and can be quantified with a spectrophotometer. Non-limiting examples of fluorescent labels that can be used in the assays described herein include Cy5, rhodamine, infrared IRDye® CW-800 (LICOR #929-71012), far-red IRDye® 650 (LICOR #929-70020), sodium fluorescein (Na-F), lucifer yellow (LY), 5’carboxyfluorescein, and calcein-acetoxymethylester (calcein-AM). In some embodiments, the BBB model (e.g., the tissue or cell aggregate) can be sectioned, and a compound described herein can be detected in one or more sections using mass spectrometry (e.g., MALDI-MSI analyses). In some embodiments, the ability of a compound described herein to cross the BBB through a transcellular transport system, such as receptor-mediated transport (RMT), carrier-mediated transport (CMT), or active efflux transport (AET), can be demonstrated by assays known in the art. See, e.g., Wang, et al. Drug Deliv. 2019; 26(1): 551–565. In some embodiments, assays to determine if compounds can be effluxed by the P-glycoprotein (Pgp) include monolayer efflux assays in which movement of compounds through Pgp is quantified by measuring movement of digoxin, a model Pgp substrate (see, e.g., Doan et al.2002. J Pharmacol Exp Ther. 303(3):1029-1037). Alternative in vivo assays to identify compounds that pass through the blood-brain barriers include phage-based systems (see, e.g., Peng et al.2019. ChemRxiv. Preprint doi.org/10.26434/chemrxiv.8242871.v1). In some embodiments, binding of the compounds described herein to brain tissue is quantified. For example, a brain tissue binding assay can be performed using equilibrium dialysis, and the fraction of a compound described herein unbound to brain tissue can be detected using LC-MS/MS (Cyprotex: Brain Tissue Binding Assay www.cyprotex.com/admepk/protein_binding/brain-tissue-binding/). [0405] In some embodiments, the subject has been identified or diagnosed as having a cancer with a dysregulation of an EGFR gene, an EGFR protein, or expression or activity, or level of any of the same (e.g., having an EGFR-associated cancer) (e.g., as determined using a regulatory agency-approved, e.g., FDA-approved, assay or kit). In some embodiments, the subject has a tumor that is positive for a dysregulation of an EGFR gene, an EGFR protein, or expression or activity, or level of any of the same (e.g., as determined using a regulatory agency-approved assay or kit). The subject can be a subject with a tumor(s) that is positive for a dysregulation of an EGFR gene, an EGFR protein, or expression or activity, or level of any of the same (e.g., identified as positive using a regulatory agency-approved, e.g., FDA-approved, assay or kit). The subject can be a subject whose tumors have a dysregulation of an EGFR gene, an EGFR protein, or expression or activity, or a level of the same (e.g., where the tumor is identified as such using a regulatory agency-approved, e.g., FDA-approved, kit or assay). In some embodiments, the subject is suspected of having an EGFR-associated cancer. In some embodiments, the subject has a clinical record indicating that the subject has a tumor that has a dysregulation of an EGFR gene, an EGFR protein, or expression or activity, or level of any of the same (and optionally the clinical record indicates that the subject should be treated with any of the compositions provided herein). [0406] In some embodiments of any of the methods or uses described herein, an assay used to determine whether the subject has a dysregulation of an EGFR gene, or an EGFR protein, or expression or activity or level of any of the same, using a sample from a subject can include, for example, next generation sequencing, immunohistochemistry, fluorescence microscopy, break apart FISH analysis, Southern blotting, Western blotting, FACS analysis, Northern blotting, and PCR-based amplification (e.g., RT-PCR and quantitative real-time RT-PCR). As is well known in the art, the assays are typically performed, e.g., with at least one labelled nucleic acid probe or at least one labelled antibody or antigen-binding fragment thereof. Assays can utilize other detection methods known in the art for detecting dysregulation of an EGFR gene, an EGFR protein, or expression or activity or levels of any of the same. In some embodiments, the sample is a biological sample or a biopsy sample (e.g., a paraffin-embedded biopsy sample) from the subject. In some embodiments, the subject is a subject suspected of having an EGFR-associated cancer, a subject having one or more symptoms of an EGFR-associated cancer, and/or a subject that has an increased risk of developing an EGFR-associated cancer). [0407] Activation of EGFR triggers multiple cascades of signal transduction pathways. EGFR contains at least six autophosphorylation sites that serve as docking nodes for a multitude of intracellular signaling molecules including adapter proteins and other enzymes. Therefore, rather than regulating a single linear pathway, activation of EGFR modulates entire networks of cellular signal transduction cascades. These signals affect both cell cycle progression/proliferation and apoptosis. Two signal transduction cascades that lie downstream of EGFR are the MAPK (mitogen activated protein kinase) and Akt pathways. In the MAPK pathway, EGFR activates the small GTP binding protein Ras to transfer cell growth signals through the Raf-MEK-ERK cascade, culminating in the regulation of transcription factors important for cell cycle progression. [0408] It is believed that the MAPK network involves at least twelve cloned highly conserved, proline-directed serine-threonine kinases which, when activated by cell stresses (e.g., oxidative stress, DNA damage, heat or osmotic shock, ultraviolet irradiation, ischemia-reperfusion), exogenous agents (e.g., anisomycin, Na arsenite, lipopolysaccharide, LPS) or pro-inflammatory cytokines, TNF-α and IL-1β, can phosphorylate and activate other kinases or nuclear proteins such as transcription factors in either the cytoplasm or the nucleus. [0409] The activation of the MAPK pathway may play an central role in: (1) production of proinflammatory cytokines such as IL-1β, TNF-α and IL-6; (2) induction of enzymes such as COX-2, which controls connective tissue remodeling in pathological condition; (3) expression of an intracellular enzyme such as iNOS, which regulates oxidation; (4) induction of adherent proteins such as VCAM-1 and many other inflammatory related molecules. In addition to these, the MAPK pathway may play a regulatory role in the proliferation and differentiation of cells of the immune system. Deviation from the strict control of MAPK signaling pathways has been implicated in the development of a variety of diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple types of cancers (Kim et al., Biochim Biophys Acta 1802(4):396-405 (2010)). [0410] Another aspect of the present application relates to a method of treating a MAPK-associated disease or disorder in a subject, including administering to a subject identified or diagnosed as having a MAPK-associated disease or disorder an effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as defined herein, to the subject. [0411] The term “MAPK-associated disease or disorder” as used herein refers to diseases or disorders associated with or having a dysregulation of a gene in a MAPK pathway, a protein in a MAPK pathway, or the expression or activity or level of any (e.g., one or more) of the same (e.g., any of the types of dysregulation of a gene in a MAPK pathway, a protein in a MAPK pathway, or the expression or activity or level of any of the same, as described herein). Non-limiting examples of a MAPK-associated diseases or disorders include, for example, neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis) as well as hyperproliferative disorders (e.g., cancer). [0412] EGFR can activate PI3K (through homodimers or heterodimers with HER3) to initiate signals through the PDK1-Akt pathway. Akt can positively regulate anti-apoptotic factors within the cell to promote cell survival. In addition, Akt can activate the protein kinase mTOR (mammalian target of rapamycin) to promote cell growth and proliferation. mTOR is a major regulator of cell growth and proliferation in response to both growth factors and cellular nutrients. It is a key regulator of the rate-limiting step for translation of mRNA into protein, the binding of the ribosome to mRNA. Here mTOR directly modulates the activities of a number of downstream signaling proteins involved in protein synthesis. [0413] Also provided herein is a method of treating an AKT-associated disease or disorder in a subject, including administering to a subject identified or diagnosed as having a AKT-associated disease or disorder an effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as defined herein, to the subject. [0414] The term “AKT-associated disease or disorder” as used herein refers to diseases or disorders associated with or having a dysregulation of a gene in a AKT pathway, a protein in a AKT pathway, or the expression or activity or level of any (e.g., one or more) of the same (e.g., any of the types of dysregulation of a gene in a AKT pathway, a protein in a AKT pathway, or the expression or activity or level of any of the same, as described herein). Non-limiting examples of a AKT-associated diseases or disorders include, for example, AKT-associated diseases or disorders, such as hyperproliferative disorders including lymphomas, melanomas, prostate cancer, breast cancer, prostate cancer, ovarian cancer, pancreatic cancer, thyroid cancer, and colorectal cancer; cancer metastasis; as well as inflammatory disorders, including diabetes, and schizophrenia. [0415] The present invention also provides methods for the treatment of disorders associated with aberrant mitogen extracellular kinase activity, including, but not limited to stroke, heart failure, hepatomegaly, cardiomegaly, diabetes, Alzheimer's disease, cystic fibrosis, symptoms of xenograft rejections, septic shock or asthma. Effective amounts of compounds of the present invention can be used to treat such disorders. [0416] The phrase "aberrant kinase activity" or "aberrant tyrosine kinase activity," includes any abnormal expression or activity of the gene encoding the kinase or of the polypeptide it encodes. Examples of such aberrant activity, include, but are not limited to, over- expression of the gene or polypeptide; gene amplification; mutations which produce constitutively-active or hyperactive kinase activity; gene mutations, deletions, substitutions, additions, etc. [0417] Also provided is a method for inhibiting EGFR activity in a mammalian cell, including contacting the mammalian cell with a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. In some embodiments, the contacting is in vivo, wherein the method includes administering an effective amount of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof to a subject having a mammalian cell having EGFR activity. In some embodiments, the mammalian cell is a mammalian cancer cell. In some embodiments, the mammalian cancer cell is any cancer as described herein. In some embodiments, the mammalian cancer cell is an EGFR pathway-associated cancer cell (e.g., an EGFR-associated cancer). [0418] As used herein, the term “contacting” refers to the bringing together of indicated moieties in an in vitro system or an in vivo system. For example, “contacting” an EGFR protein with a compound provided herein includes the administration of a compound provided herein to a subject, such as a human, having an EGFR protein, as well as, for example, introducing a compound provided herein into a sample containing a mammalian cellular or purified preparation containing the EGFR protein. [0419] Also provided herein is a method of inhibiting mammalian cell proliferation, in vitro or in vivo. The method includes contacting a mammalian cell with an effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as defined herein. B. Combination Treatments [0420] The compounds of this invention can be administered as the sole pharmaceutical agent or in combination with one or more other pharmaceutical agents where the combination causes no unacceptable adverse effects. In the field of medical oncology, it is normal practice to use a combination of different forms of treatment to treat each subject with cancer. In medical oncology the other component(s) of such conjoint treatment or therapy in addition to compositions provided herein may be, for example, surgery, radiotherapy, and chemotherapeutic agents, such as Ras pathway inhibitors, kinase inhibitors, signal transduction inhibitors, and/or monoclonal antibodies. For example, a surgery may be open surgery or minimally invasive surgery. Compounds of the invention, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, therefore, may also be useful as adjuvants to cancer treatment, that is, they can be used in combination with one or more additional therapies or therapeutic agents, for example, a chemotherapeutic agent that works by the same or by a different mechanism of action. In some embodiments, a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof can be used prior to administration of an additional therapeutic agent or additional therapy. For example, a subject in need thereof can be administered one or more doses of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for a period of time and then undergo at least partial resection of the tumor. In some embodiments, the treatment with one or more doses of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof reduces the size of the tumor (e.g., the tumor burden) prior to the at least partial resection of the tumor. In some embodiments, a subject in need thereof can be administered one or more doses of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof for a period of time and under one or more rounds of radiation therapy. In some embodiments, the treatment with one or more doses of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof reduces the size of the tumor (e.g., the tumor burden) prior to the one or more rounds of radiation therapy. [0421] In some embodiments, the one or more additional therapies or therapeutic agents are independently selected from those therapeutic agents described supra. [0422] In some embodiments, the compound of the invention and the one or more additional therapies or therapeutic agents are both administered to a subject simultaneously in the form of a single composition or dosage. Alternatively, the compound of the invention and the one or more additional therapies or therapeutic agents are both administered to a subject sequentially with variable intervening time limits. [0423] Accordingly, also provided herein is a method of treating a cancer, including administering to a subject in need thereof a pharmaceutical combination for treating cancer which includes (a) a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, and (b) an additional therapeutic agent, wherein the compound of the invention and the additional therapeutic agent are administered simultaneously, separately or sequentially, wherein the amounts of the compound of the invention, or pharmaceutically acceptable salt thereof, and the additional therapeutic agent are together effective in treating the cancer. In some embodiments, the compound of the invention, or pharmaceutically acceptable salt thereof, and the additional therapeutic agent are administered simultaneously as separate dosages. In some embodiments, the compound of the invention, or pharmaceutically acceptable salt thereof, and the additional therapeutic agent are administered as separate dosages sequentially in any order, in jointly effective amounts, e.g., in daily or intermittently dosages. In some embodiments, the compound of the invention, or pharmaceutically acceptable salt thereof, and the additional therapeutic agent are administered simultaneously as a combined dosage. In some embodiments, the cancer is an EGFR pathway-associated cancer (e.g., an EGFR-associated cancer). [0424] Accordingly, also provided herein are methods for inhibiting, preventing, aiding in the prevention, or decreasing the symptoms of metastasis of a cancer in a subject in need thereof. The method includes administering to the subject an effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof. Such methods can be used in the treatment of one or more of the cancers described herein. See, e.g., US Publication No. 2013/0029925; International Publication No. WO 2014/083567; and US Patent No.8,568,998. See also, e.g., Hezam K et al., Rev Neurosci 2018 Jan 26;29:93-98; Gao L et al., Pancreas 2015 Jan; 44:134-143; Ding K et al., J Biol Chem 2014 Jun 6; 289:16057-71; and Amit M et al., Oncogene 2017 Jun 8; 36:3232- 3239. In some embodiments, the cancer is an EGFR pathway-associated cancer (e.g., an EGFR- associated cancer). In some embodiments, the compound of the invention, or a pharmaceutically acceptable salt thereof, is used in combination with an additional therapy or another therapeutic agent, such as those described herein. [0425] Also provided herein is a compound of the invention, or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof as defined herein for use in the treatment of cancer and/or inhibiting metastasis associated with a particular cancer. [0426] The term “metastasis” is an art known term and means the formation of an additional tumor (e.g., a solid tumor) at a site distant from a primary tumor in a subject, where the additional tumor includes the same or similar cancer cells as the primary tumor. [0427] Also provided are methods of decreasing the risk of developing a metastasis or an additional metastasis in a subject having an EGFR-associated cancer that include: selecting, identifying, or diagnosing a subject as having an EGFR-associated cancer, and administering an effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof to the subject selected, identified, or diagnosed as having an EGFR-associated cancer. Also provided are methods of decreasing the risk of developing a metastasis or an additional metastasis in a subject having an EGFR-associated cancer that includes administering an effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof to a subject having an EGFR-associated cancer. The decrease in the risk of developing a metastasis or an additional metastasis in a subject having an EGFR-associated cancer can be compared to the risk of developing a metastasis or an additional metastasis in the subject prior to treatment, or as compared to a subject or a population of subjects having a similar or the same EGFR-associated cancer that has received no treatment or a different treatment. In some embodiments, the additional therapeutic agent is selected from any of the therapeutic agents identified herein. In some embodiments, the subject has been administered one or more doses of a compound of the invention, or a pharmaceutically acceptable salt thereof, prior to administration of the pharmaceutical composition. [0428] The phrase “risk of developing a metastasis” means the risk that a subject having a primary tumor will develop an additional tumor (e.g., a solid tumor) at a site distant from a primary tumor in a subject over a set period of time, where the additional tumor includes the same or similar cancer cells as the primary tumor. Methods for reducing the risk of developing a metastasis in a subject having a cancer are described herein. [0429] The phrase “risk of developing additional metastases” means the risk that a subject having a primary tumor and one or more additional tumors at sites distant from the primary tumor (where the one or more additional tumors include the same or similar cancer cells as the primary tumor) will develop one or more further tumors distant from the primary tumor, where the further tumors include the same or similar cancer cells as the primary tumor. Methods for reducing the risk of developing additional metastasis are described herein. C. Compounds, Pharmaceutically Acceptable Salts, and Compositions for Use [0430] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use as a medicament. [0431] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in inhibiting EGFR. [0432] Compounds of the invention, pharmaceutically acceptable salts and solvates thereof, and pharmaceutical compositions thereof are also useful for treating an EGFR-associated cancer. As such, also provided herein is a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in the treatment of cancer. [0433] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating cancer. In some embodiments, the cancer is an EGFR-associated cancer. In some embodiments, the cancer is associated with a dysregulation of an EGFR pathway gene, an EGFR pathway protein, or expression or activity or level of any of the same. [0434] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating an EGFR pathway-associated cancer. In some embodiments, the EGFR pathway-associated cancer is selected from a RAS-associated cancer, an ErbB2-associated cancer, an ErbB3-associated cancer, an ErbB4-associated cancer, a NF1-associated cancer, a PDGFR-A-associated cancer, a PDGFR-B-associated cancer, a FGFR1-associated cancer, FGFR2-associated cancer, FGFR3-associated cancer, a IGF1 R-associated cancer, a INSR-associated cancer, a ALK-associated cancer, a ROS-associated cancer, a TrkA-associated cancer, a TrkB-associated cancer, a TrkC-associated cancer, a RET-associated cancer, a c-MET-associated cancer, a VEGFR1-associated cancer, a VEGFR2-associated cancer, a VEGFR3-associated cancer, an AXL-associated cancer, a SHP2-associated cancer, a RAF-associated cancer (e.g., a BRAF-associated cancer), a PI3K-associated cancer, an AKT-associated cancer, an mTOR-associated cancer, a MEK-associated cancer, an ERK-associated cancer, or a combination thereof). [0435] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating a cancer associated with a dysregulation of an EGFR gene, an EGFR protein, or the expression or activity or level of any of the same. [0436] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating an EGFR-associated cancer in a subject. [0437] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating an EGFR pathway-associated disease or disorder in a subject. In some embodiments, the EGFR pathway-associated disease or disorder is an EGFR-associated cancer. In some embodiments, the EGFR pathway-associated cancer is a MAPK-associated cancer, a Pi3K associated cancer and/or an AKT-associated cancer. [0438] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating cancer in a subject, wherein the subject is determined to have a cancer associated with a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same. In some embodiments, the subject was previously treated with another anticancer treatment, e.g., at least partial resection of the tumor or radiation therapy. In some embodiments, the subject is determined to have an EGFR-associated cancer through the use of a regulatory agency-approved test or assay for identifying dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, in a subject or a biopsy sample from the subject or by performing any of the non-limiting examples of assays described herein. In some embodiments, the test or assay is provided as a kit. [0439] Also provided is a compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in treating an EGFR-associated cancer in a subject identified or diagnosed as having an EGFR-associated cancer through a step of performing an assay (e.g., an in vitro assay) on a sample obtained from the subject to determine whether the subject has a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, where the presence of a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, identifies that the subject has an EGFR-associated cancer. [0440] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating a subject diagnosed with or identified as having an EGFR-associated cancer. [0441] In some embodiments, the invention relates to a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating non-small cell lung cancer in a subject in need thereof. In some embodiments, the invention relates to a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating EGFR-associated non-small cell lung cancer in a subject in need thereof. In some embodiments, the invention relates to a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating EGFR-mutated non-small cell lung cancer in a subject in need thereof. [0442] In some embodiments, the invention relates to a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating non-small cell lung cancer in a subject. In some embodiments, the invention relates to a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating EGFR-associated non-small cell lung cancer in a subject. In some embodiments, the invention relates to a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating EGFR-mutated non-small cell lung cancer in a subject. [0443] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating one or more gliomas. In some embodiments, the one or more gliomas is selected from glioblastoma (also known as glioblastoma multiforme), astrocytomas, oligodendrogliomas, ependymomas, and mixed gliomas, meningiomas, medulloblastomas, gangliogliomas, schwannomas (neurilemmomas), and craniopharyngiomas. In some embodiments, the brain tumor is a primary brain tumor. In some embodiments, the subject has previously been treated with another anticancer agent, e.g., another EGFR pathway inhibitor (e.g., a compound that is not a compound of the invention), or an inhibitor of another tumorgenic pathway gene or protein (e.g., Ras (e.g., KRas, HRas, and/or NRas), ErbB2, ErbB3, ErbB4, NF1, PDGFR-A, PDGFR-B, FGFR1, FGFR2, FGFR3, IGF1 R, INSR, ALK, ROS, TrkA, TrkB, TrkC, RET, c-MET, VEGFR1, VEGFR2, VEGFR3, AXL, SHP2, RAF (e.g., BRAF), PI3K, AKT, mTOR, MEK, ERK, or a combination thereof). In some embodiments, the brain tumor is a metastatic brain tumor. [0444] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating a MAPK-associated disease or disorder in a subject. [0445] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating an AKT-associated disease or disorder in a subject. [0446] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in treating disorders associated with aberrant mitogen extracellular kinase activity. In some embodiments, the disorder is selected from stroke, heart failure, hepatomegaly, cardiomegaly, diabetes, Alzheimer's disease, cystic fibrosis, symptoms of xenograft rejections, septic shock, or asthma. [0447] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in inhibiting mammalian cell proliferation, in vitro or in vivo. [0448] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method wherein the subject is treated with one or more additional therapeutic agents administered concurrently with, prior to, or subsequent to treatment with an effective amount of the compound, pharmaceutically acceptable salt or pharmaceutical composition. In some embodiments, the additional therapeutic agent is selected from the agents described herein. D. Manufacture of Medicaments [0449] In another aspect, the invention provides the use of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for the manufacture of a medicament. [0450] In another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in inhibiting EGFR. [0451] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating cancer. In some embodiments, the cancer is an EGFR-associated cancer. In some embodiments, the cancer is associated with a dysregulation of an EGFR pathway gene, an EGFR pathway protein, or expression or activity or level of any of the same. [0452] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating an EGFR pathway-associated cancer. In some embodiments, the EGFR pathway-associated cancer is selected from a RAS-associated cancer, an ErbB2-associated cancer, an ErbB3-associated cancer, an ErbB4-associated cancer, a NF1-associated cancer, a PDGFR-A-associated cancer, a PDGFR-B-associated cancer, a FGFR1-associated cancer, FGFR2-associated cancer, FGFR3-associated cancer, a IGF1 R-associated cancer, a INSR-associated cancer, a ALK-associated cancer, a ROS-associated cancer, a TrkA-associated cancer, a TrkB-associated cancer, a TrkC-associated cancer, a RET-associated cancer, a c-MET-associated cancer, a VEGFR1-associated cancer, a VEGFR2-associated cancer, a VEGFR3-associated cancer, an AXL-associated cancer, a SHP2-associated cancer, a RAF-associated cancer (e.g., a BRAF-associated cancer), a PI3K-associated cancer, an AKT-associated cancer, an mTOR-associated cancer, a MEK-associated cancer, an ERK-associated cancer, or a combination thereof). [0453] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating a cancer associated with a dysregulation of an EGFR gene, an EGFR protein, or the expression or activity or level of any of the same. [0454] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating an EGFR-associated cancer in a subject. [0455] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating an EGFR pathway-associated disease or disorder in a subject. In some embodiments, the EGFR pathway-associated disease or disorder is an EGFR-associated cancer. In some embodiments, the EGFR pathway-associated cancer is a MAPK-associated cancer, a Pi3K associated cancer and/or an AKT-associated cancer. [0456] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating cancer in a subject, wherein the subject is determined to have a cancer associated with a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same. In some embodiments, the subject was previously treated with another anticancer treatment, e.g., at least partial resection of the tumor or radiation therapy. In some embodiments, the subject is determined to have an EGFR-associated cancer through the use of a regulatory agency-approved test or assay for identifying dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, in a subject or a biopsy sample from the subject or by performing any of the non-limiting examples of assays described herein. In some embodiments, the test or assay is provided as a kit. [0457] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating an EGFR-associated cancer in a subject identified or diagnosed as having an EGFR-associated cancer through a step of performing an assay (e.g., an in vitro assay) on a sample obtained from the subject to determine whether the subject has a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, where the presence of a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, identifies that the subject has an EGFR-associated cancer. [0458] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating a subject diagnosed with or identified as having an EGFR-associated cancer. [0459] In some embodiments, the invention relates to the use of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, in the manufacture of a medicament for use in treating non-small cell lung cancer in a subject in need thereof. In some embodiments, the invention relates to the use of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, in the manufacture of a medicament for use in treating EGFR-associated non-small cell lung cancer in a subject in need thereof. In some embodiments, the invention relates to the use of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, in the manufacture of a medicament for use in treating EGFR-mutated non-small cell lung cancer in a subject in need thereof. [0460] In some embodiments, the invention relates to the use of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, in the manufacture of a medicament for use in treating non-small cell lung cancer in a subject. In some embodiments, the invention relates to the use of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, in the manufacture of a medicament for use in treating EGFR-associated non-small cell lung cancer in a subject. In some embodiments, the invention relates to the use of a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, in the manufacture of a medicament for use in treating EGFR-mutated non-small cell lung cancer in a subject. [0461] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating one or more gliomas. In some embodiments, the one or more gliomas is selected from glioblastoma (also known as glioblastoma multiforme), astrocytomas, oligodendrogliomas, ependymomas, and mixed gliomas, meningiomas, medulloblastomas, gangliogliomas, schwannomas (neurilemmomas), and craniopharyngiomas. In some embodiments, the brain tumor is a primary brain tumor. In some embodiments, the subject has previously been treated with another anticancer agent, e.g., another EGFR pathway inhibitor (e.g., a compound that is not a compound of the invention), or an inhibitor of another tumorgenic pathway gene or protein (e.g., Ras (e.g., KRas, HRas, and/or NRas), ErbB2, ErbB3, ErbB4, NF1, PDGFR-A, PDGFR-B, FGFR1, FGFR2, FGFR3, IGF1 R, INSR, ALK, ROS, TrkA, TrkB, TrkC, RET, c-MET, VEGFR1, VEGFR2, VEGFR3, AXL, SHP2, RAF (e.g., BRAF), PI3K, AKT, mTOR, MEK, ERK, or a combination thereof). In some embodiments, the brain tumor is a metastatic brain tumor. [0462] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating a MAPK-associated disease or disorder in a subject. [0463] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating an AKT-associated disease or disorder in a subject. [0464] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in treating disorders associated with aberrant mitogen extracellular kinase activity. In some embodiments, the disorder is selected from stroke, heart failure, hepatomegaly, cardiomegaly, diabetes, Alzheimer's disease, cystic fibrosis, symptoms of xenograft rejections, septic shock, or asthma. [0465] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in inhibiting mammalian cell proliferation, in vitro or in vivo. [0466] Also provided is the use of a compound of the invention, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating an EGFR-associated cancer in a subject identified or diagnosed as having an EGFR-associated cancer through a step of performing an assay on a sample obtained from the subject to determine whether the subject has a dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same where the presence of dysregulation of an EGFR gene, an EGFR protein, or expression or activity or level of any of the same, identifies that the subject has an EGFR-associated cancer. [0467] In yet another aspect, the invention provides the use of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the manufacture of a medicament for use in combination with one or more additional therapeutic agents administered concurrently with, prior to, or subsequent to treatment with the compound or pharmaceutical composition. In some embodiments, the additional therapeutic agent is selected from the agents described herein. VI. ENUMERATED EMBODIMENTS [0468] Additional embodiments, features, and advantages of the disclosure will be apparent from the following detailed description and through practice of the disclosure. The compounds and methods of the present disclosure can be described as embodiments in any of the following enumerated clauses. It will be understood that any of the embodiments described herein can be used in connection with any other embodiments described herein to the extent that the embodiments do not contradict one another. [0469] 1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein: Ring A is an aryl or 5- to 10-membered heteroaryl; X is CH or N; R¹ is hydrogen or C₁-C₃ alkyl; R², R³, R⁴ and R⁵ are independently selected at each occurrence from the group consisting of hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy and –(C₁-C₃ alkylene)-O-R¹¹, wherein R² and R³ or R⁴ and R⁵ may optionally be taken together with the atom to which they are attached to form a 3- to 6-membered cycloalkyl, or R² or R³ and R⁴ or R⁵ may optionally be taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring; R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, phenyl, C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –(CH₂)_mO(CH₂)_m-(C₁-C₃ alkoxy), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(aryl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(heteroaryl), –NH-aryl, –C(O)-( 4- to 7-membered heterocyclyl), heteroaryl, 4- to 10-membered heterocyclyl, 3- to 6-membered cycloalkyl, –CH₂S(O)₂CH₃, –CH₂S(O)NCH₃ and cyano; R⁷ is selected from hydrogen, halo, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₄ alkylene-(C₁-C₃ alkoxy), 3- to 6-membered cycloalkyl, –O-(3- to 6-membered cycloalkyl), –O-heteroaryl, –O-(C₁-C₄ alkylene)-(C₁-C₃ alkoxy), –O-(C₁-C₃ alkoxy)-heteroaryl, –O-(C₁-C₄ alkylene)-(4- to 7-membered heterocyclyl), –O-(C₁-C₄ alkylene)-O-(3- to 6-membered cycloalkyl), –NH-CH₂-heteroaryl, –O-CH₂-heteroaryl and ; R⁸ is hydrogen, C₁-C₃ alkyl, or C₁-C₆ haloalkyl; or R⁷ and R⁸ are taken together to form a fused bicyclic heteroaromatic ring; R⁹ is independently selected at each occurrence thereof from the group consisting of halogen, cyano, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl and –O-(C₁-C₃ haloalkyl); R¹⁰ is selected from heterocyclyl, cycloalkyl and heteroaryl; R¹¹ is C₁-C₃ alkyl or heteroaryl; m is 0, 1, 2 or 3; and n is 0, 1, 2, 3, 4 or 5; wherein each alkyl is optionally substituted with one or more substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₃-C₆ cycloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy and –OCD₃; each cycloalkyl is optionally substituted with one to three substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy and –OCD₃; each heterocyclyl ring is optionally substituted with one to four substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₃-C₆ cycloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy, OCD₃, -S(O)₂CH₃, –C(O)-C₁-C₃ alkyl, and 5-membered heteroaryl optionally substituted with one C₁-C₃ alkyl; each aryl is optionally substituted with one to three substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl and C₁-C₃ alkoxy; and each heteroaryl, or bicyclic heteroaryl is optionally substituted with one to three substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, , an optionally substituted –O-(C₃-C₆ cycloalkyl) and an optionally substituted -O-(4- to 6-membered heterocyclyl). [0470] 2. The compound of clause 1, where Ring A is phenyl. [0471] 3. The compound of clause 1, wherein X is CH. [0472] 4. The compound of clause 1, wherein X is N. [0473] 5. The compound of any one of clauses 1-4, wherein R¹ is hydrogen or methyl. [0474] 6. The compound of any one of clauses 1-5, wherein R², R³, R⁴ and R⁵ are hydrogen. [0475] 7. The compound of any one of clauses 1-5, wherein R² and R³ or R⁴ and R⁵ are taken together to form a 3- to 6-membered cycloalkyl. [0476] 8. The compound of any one of clauses 1-5, wherein R⁵ is selected from hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy and -(C₁-C₃ alkylene)-O-R¹¹. [0477] 9. The compound of clause 8, wherein R¹¹ is methyl or heteroaryl. [0478] 10. The compound of any one of clauses 1-6, wherein R⁶ is hydrogen or C₁-C₃ alkyl. [0479] 11. The compound of any one of clauses 1-10, wherein: R⁷ is hydrogen, -O-CH₂-heteroaryl

R⁸ is hydrogen. [0480] 12. The compound of any one of clauses 1-10, wherein R⁷ and R⁸ are taken together to form a fused bicyclic heteroaromatic ring. [0481] 13. The compound of any one of clauses 1-12, wherein n is 0. [0482] 14. The compound of any one of clauses 1-12, wherein R⁹ is halogen. [0483] 15. The compound of any one of clauses 1-12, wherein R⁹ is C₁-C₃ alkoxy. [0484] 16. The compound of any one of clauses 1-12, wherein Ring A is a 5- to 10-membered heteroaryl. ,

, ,

,

,

,

[0486] 18. The compound of any one of clauses 1-17, wherein the compound is an EGFR inhibitor selective to a mutant EGFR protein or gene. [0487] 19. A pharmaceutical composition comprising a compound of any one of clauses 1-17, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. [0488] 20. A method for treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of a compound of any one of clauses 1-17. [0489] 21. The method according to clause 20, wherein the cancer is an EGFR-associated cancer. VII. GENERAL SYNTHETIC METHODS FOR PREPARING COMPOUNDS [0490] The compounds of the invention can be prepared from known materials by the methods described in the Examples, other similar methods, and other methods known to one skilled in the art. As one skilled in the art would appreciate, the functional groups of the intermediate compounds in the methods described below may need to be protected by suitable protecting groups. Protecting groups may be added or removed in accordance with standard techniques, which are well-known to those skilled in the art. The use of protecting groups is described in detail in T.G.M. Wuts et al., Greene’s Protective Groups in Organic Synthesis (4th ed.2006). [0491] The following schemes can be used to practice the various embodiments disclosed herein. It will be understood that these schemes are merely exemplary and that they provide ready access to core structures with variable functionality. For a more detailed description of the individual reaction steps, see the Examples section below. Those skilled in the art will appreciate that other synthetic routes may be used. Although some specific starting materials and reagents are depicted in the Schemes and discussed below, other starting materials and reagents can be substituted to provide a variety of derivatives or reaction conditions. In addition, many of the compounds prepared by the methods described below can be further modified in light of this disclosure using conventional chemistry well known to those skilled in the art. [0492] Generally, the compounds of the invention can be prepared by one or more of the processes outlined in General Synthetic Schemes 1-4, below. As used in the compounds of the General Synthetic Schemes, the definitions of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, and X are the same as those recited above with respect to formula (I). Where the schemes refer to R¹⁰, R¹¹, R¹², and R¹³, one will appreciate that these are alternative, location-specific substituents equivalent in scope to R⁹ as recited above with respect to formula (I). [0493] General Synthetic Scheme 1: Preparation of compounds of Formula (I). 1

[0494] General Synthetic Scheme 2: Preparation of compounds of Formula (I).

IV IX LG¹ = halogen preferabaly Cl or Br LG² = halogen preferabaly I PG = protecting groups such as Boc, Bn, FMoc, SEM, etc. 1

[0495] General Synthetic Scheme 3: Preparation of compounds of Formula (I).

[0496] General Synthetic Scheme 4. Preparation of compounds of Formula (I).

[0497] Some compounds in following schemes are depicted with generalized substituents; however, one skilled in the art will immediately appreciate that the nature of the substituents can varied to afford the various compounds contemplated in the present embodiments. Moreover, the reaction conditions are exemplary and alternative conditions are well known. The reaction sequences in the following examples are not meant to limit the scope of the embodiments as set forth in the claims. EXAMPLES I. GENERAL METHODS [0498] The compounds provided herein, including salts thereof, can be prepared using known organic synthesis techniques and can be synthesized according to any of numerous possible synthetic routes. [0499] The reactions for preparing the compounds provided herein can be carried out in suitable solvents which can be readily selected by one of skill in the art of organic synthesis. Suitable solvents can be substantially non-reactive with the starting materials (reactants), the intermediates, or products at the temperatures at which the reactions are carried out, e.g., temperatures which can range from the solvent's freezing temperature to the solvent's boiling temperature. A given reaction can be carried out in one solvent or a mixture of more than one solvent. Depending on the particular reaction step, suitable solvents for a particular reaction step can be selected by the skilled artisan. [0500] Preparation of the compounds provided herein can involve the protection and deprotection of various chemical groups. The need for protection and deprotection, and the selection of appropriate protecting groups, can be readily determined by one skilled in the art. The chemistry of protecting groups can be found, for example, in Protecting Group Chemistry, 1^st Ed., Oxford University Press, 2000; March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5^th Ed., Wiley- Interscience Publication, 2001; and Peturssion, S. et al., “Protecting Groups in Carbohydrate Chemistry,” J. Chem. Educ., 74(11), 1297 (1997). [0501] Reactions can be monitored according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g., ¹H or ¹³C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), mass spectrometry, or by chromatographic methods such as high performance liquid chromatography (HPLC), liquid chromatography-mass spectroscopy (LCMS), or thin layer chromatography (TLC). Compounds can be purified by those skilled in the art by a variety of methods, including high performance liquid chromatography (HPLC) (“Preparative LC-MS Purification: Improved Compound Specific Method Optimization” K.F. Blom, et al., J. Combi. Chem.6(6), 874 (2004), normal phase silica chromatography, and supercritical fluid chromatography (SFC). [0502] The following Examples are provided to illustrate exemplary embodiments of the compounds disclosed herein and their preparation. II. ABBREVIATIONS [0503] Unless otherwise noted, or where the context dictates otherwise, the following abbreviations shall be understood to have the following meanings: Abbreviation Meaning AA ammonium acetate ACN or MeCN acetonitrile appt apparent triplet apps apparent singlet AcOH acetic acid Aq. aqueous Bispin bis(pinacolato)diboron Boc tert-butoxycarbonyl (Boc)₂O Di-tert-butyl dicarbonate brs broad singlet CO carbon monoxide con. concentrated Abbreviation Meaning d doublet dd doublet of doublet DCM dichloromethane DIPEA or DIEA N,N-diisopropylethylamine Dikis bis(triphenylphosphine)palladium(II) dichloride DMAc N,N-dimethylacetamide DME dimethoxyethane DMF N,N-dimethylformamide DMSO dimethylsulfoxide EDCI 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Et ethyl EtOAc or EA ethyl acetate EtOH ethanol ESI electrospray ionization FA formic acid HATU (1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5- b]pyridinium 3-oxide hexafluorophosphate HOBt 1-hydroxybenzotriazole IPA 2-propanol LDA lithium diisopropylamide LiOH lithium hydroxide LAH or LiAlH₄ lithium aluminium hydride m/z mass-to-charge ratio Me methyl MeI iodomethane MeOH methanol MSA Metanesulfonic acid MsCl methanesulfonyl chloride MTBA Methyl tert-butyl ether NaOMe sodium methoxide NaO-tBu sodium tert-butoxide NaN₃ sodium azide NaSMe sodium thiomethoxide NBS N-bromosuccinimide _NH2OH^HCl ^{hydroxylamine hydrochloride} NMP N-methyl pyrrolidinone obsd. observed OB reagent Ohira-Bestmann reagent Abbreviation Meaning Pd(OAc)₂ palladium (II) acetate Pd(dppf)Cl₂ (1,1'-Bis(diphenylphosphino)ferrocene)palladium(II) dichloride PE petroleum ether PhI(OAc)₂ (Diacetoxyiodo)benzene PPh₃ triphenylphosphine s singlet SEM 2-(Trimethylsilyl)ethoxymethyl SEM-Cl 2-(Trimethylsilyl)ethoxymethyl chloride SPhos-Pd-G3 (2-Dicyclohexylphosphino-2′,6′-dimethoxybiphenyl)[2-(2′-amino-1,1′- biphenyl)]palladium(II) methanesulfonate t-BuXphos PdG3 [(2-Di-tert-butylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′- amino-1,1′-biphenyl)] palladium(II) methanesulfonate TBACN tetrabutylammoniumcyanide td triplet of doublet Tetrakis tetrakis(triphenylphosphine)palladium(0) TES triethylsilane Tf trifluoromethanesulfonyl TfOH trifluoromethanesulfonic acid T₃P Propylphosphonic anhydride t triplet TBAF tetrabutylammonium fluoride TEA/Et₃N triethylamine TFA trifluoroacetic acid THF tetrahydrofuran TMSOTf trimethylsilyl trifluoromethanesulfonate TMSI trimethylsilyl iodide °C degrees Celsius rt Room temperature NMR Nuclear magnetic resonance ¹H NMR proton nuclear magnetic resonance ESI-MS Electrospray mass spectrometry MS Mass spectrum LC/MS Liquid chromatography-mass spectrometry UPLC Ultra performance liquid chromatography HPLC/MS/MS High performance liquid chromatography/tandem mass spectrometry IS Internal standard HPLC High performance liquid chromatography SFC Supercritical fluid chromatography Abbreviation Meaning ESI Electrospray ionization MW microwave TLC Thin-layer chromatography kg Kilogram g Grams mg Milligrams L Liter(s) mL Milliliters μL Microliters nL Nanoliters mol Mole mmol Millimoles hr, h Hours min Minutes ms Millisecond mm Millimeters μm Micrometers nm Nanometer MHz Megahertz Hz Hertz N Normal (concentration) M Molar (concentration) mM Millimolar (concentration) μM Micromolar (concentration) ppm Parts per million % w/v Weight-volume concentration % w/w Weight-weight concentration

III. INTERMEDIATES USED IN THE PREPARATION OF THE EXAMPLE COMPOUNDS: Intermediate 1: 8-chloro-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-1)

Step-1: methyl 4-bromo-3-chloro-1H-pyrrole-2-carboxylate (1-2) [0504] To a stirred solution of methyl 3-chloro-1H-pyrrole-2-carboxylate (1-1) (40 g) in ACN was added NBS (44 g) at RT. The RM was stirred at RT for 24 h, diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (5% ethyl acetate in hexane) to afford the title compound (1-2). MS (ESI⁺): m/z 236.07 [M (⁷⁹Br)–H]⁺, 238.07 [M (⁸¹Br)–H]⁺. Step-2: methyl 4-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-3-chloro-1H-pyrrole-2-carboxylate (1-3) [0505] A mixture of methyl 4-bromo-3-chloro-1H-pyrrole-2-carboxylate (1-2) (45 g), tert-butyl (2-hydroxyethyl) carbamate (46 g) and PPh₃ (99 g) in THF was treated with DIAD (76 g) at RT for 2 h, diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (20% ethyl acetate in hexane) to afford the title compound (1-3). MS (ESI⁺): m/z 381.09 [M (⁷⁹Br)+H]⁺, 383.09 [M (⁸¹Br)+H]⁺. Step-3: methyl 4-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-3-chloro-1H-pyrrole-2-carboxylate (1-4) [0506] To a stirred solution of methyl 4-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-3-chloro- 1H-pyrrole-2-carboxylate (1-3) (5 g) in 1,4-dioxane: water (4:1 ratio) was added pyridin-4-ylboronic acid (2.4 g) and Na₂CO₃ (5.4 g) at RT. The RM was purged under a stream of argon for 15 min and treated with Tetrakis Pd(0) (0.5 g). The RM was stirred at 100 °C for 24 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (5% methanol in DCM) to afford the title compound (1-4). MS (ESI⁺): m/z 380.17 [M+H]⁺. Step-4: 8-chloro-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-1) [0507] An ice-cold solution of methyl 1-(2-((tert-butoxycarbonyl)amino)ethyl)-3-chloro-4-(pyridin- 4-yl)-1H-pyrrole-2-carboxylate (1-4) (22 g) in DCM was treated with TFA. The RM stirred at RT for 24 h and concentrated under reduced pressure. The residue was then diluted with DCM and neutralized to pH ~7 with saturated aqueous NaHCO₃ solution. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude methyl 1-(2-aminoethyl)-3-chloro-4- (pyridin-4-yl)-1H-pyrrole-2-carboxylate, which was dissolved in methanol and treated with CS₂CO₃ (8.7 g). The RM was stirred at RT for 24 h, evaporated and purified by column chromatography on silica gel (5% methanol in DCM) to afford the title compound (Int-1). MS (ESI⁺): m/z 248.20 [M+H]⁺. [0508] The intermediates listed in Table 1 (Int-2 and Int-3) were prepared using similar methods to those described for the synthesis of Int-1 by changing corresponding alcohol (step-2) and the analytical data are described below. [0509] Table 1. Intermediate-2 and Intermediate-3.

Intermediate 4: 8-((2,3-difluorophenyl)amino)-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-4)

Step-1: 8-chloro-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (4-1) [0510] NaH (60% dispersion in mineral oil) (97 mg) was treated with an ice-cold solution of 8- chloro-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (500 mg) in DMF and stirred for 30 min, followed by the addition of PMB-Cl (348 mg) in DMF at 0 °C. The RM was stirred at RT for 2 h, diluted with ice-cold water and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (1.5% methanol in DCM) to afford the title compound (4-1). MS (ESI⁺): m/z 368.49 [M+H]⁺. Step-2: 8-((2,3-difluorophenyl)amino)-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Int-4) [0511] To a stirred solution of 8-chloro-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (450 mg) in 1,4-dioxane was added 2,3-difluoroaniline (237 mg) and CS₂CO₃ (1.2 g) at RT. The RM was purged under a stream of argon for 10 min before the addition of Xantphos (141 mg) and Pd₂(dba)₃ (112 mg). The RM was heated at 120 °C for 36 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (1.3% methanol in DCM) to afford the title compound (Int-4). MS (ESI⁺): m/z 461.00 [M+H]⁺. [0512] The intermediate shown in Table 2 (Int-5) was prepared using similar methods to those described for the synthesis of Int-4 by changing corresponding aniline (step-2) and the analytical data are described below. [0513] Table 2. Intermediate-5

Intermediate 6: 8-(benzo[d]thiazol-4-ylamino)-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-6)

Step-1: methyl 3-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrole-2-carboxylate (6-2) [0514] Prepared using a similar method described for the synthesis of (1-3). MS (ESI⁺): m/z 347.21 [M (⁷⁹Br)+H]⁺, 349.21 [M (⁸¹Br)+H]⁺. Step-2: methyl 3-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-4-iodo-1H-pyrrole-2-carboxylate (6-3) [0515] To a stirred solution of methyl 3-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrole- 2-carboxylate (6-2) (1 g) in DMF was added NIS (0.6 g) at RT. The RM was stirred at RT for 16 h, diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (20% ethyl acetate in hexane) to afford the title compound (6-3). MS (ESI⁺): m/z 373.09 [M (⁷⁹Br)-100]⁺, 375.09 ([M (⁸¹Br) -100]⁺. Step-3: methyl 3-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-4-(pyridin-4-yl)-1H-pyrrole-2- carboxylate (6-4) [0516] To a stirred solution of methyl 3-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-4-iodo-1H- pyrrole-2-carboxylate (6-3) (10 g) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (8.3 g) in 1,4-dioxane were added Na₂CO₃ (16 g) in water (20 mL) at RT. The RM was purged with argon gas for 10 min before the addition of Pd(dppf)Cl₂ (1.6 g). The RM was heated at 100 °C for 16 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (5% methanol in DCM) to afford the title compound (6-4). MS (ESI⁺): m/z 424.25 [M (⁷⁹Br)+H]⁺, 426.25 [M (⁸¹Br)+H]⁺. Step-4: 8-bromo-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (6-5) [0517] Prepared using a similar method described for the synthesis of (Int-1). MS (ESI⁺): m/z 292.10 [M (⁷⁹Br)+H]⁺, 294.10 [M (⁸¹Br)+H]⁺. Step-5: 8-bromo-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (6-6) [0518] Prepared using a similar method described for the synthesis of (4-1). MS (ESI⁺): m/z 411.92 [M (⁷⁹Br)+H]⁺, and 412.92 [M (⁸¹Br)+H]⁺. Step-6: 8-(benzo[d]thiazol-4-ylamino)-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Int-6) [0519] To a stirred solution of 8-bromo-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (6-6) (400 mg) and 1,3-benzothiazol-4-amine (218 mg) in DMAc was added Cs₂CO₃ (1.1 g) at RT. The RM was purged under a stream of argon for 15 min and treated with xantphos (561 mg) and Pd₂(dba)₃ (710 mg). The RM was heated at 170 °C for 16 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (2.5% methanol in DCM) to afford the title compound (Int-6). MS (ESI⁺): m/z 482.35 [M+H]⁺. [0520] The intermediate listed in Table 3 (Int-7) was prepared using similar methods to those described for the synthesis of Int-6 by changing corresponding aniline (step-2) and the analytical data are described below. [0521] Table 3. Intermediate-7

Intermediate 8: 8'-bromo-7'-iodo-2'-(4-methoxybenzyl)-4'H-spiro[cyclobutane-1,3'-pyrrolo[1,2- a]pyrazin]-1'(2'H)-one (Int-8)

Step-1: methyl 3-bromo-1-((1-((tert-butoxycarbonyl)amino)cyclobutyl)methyl)-1H-pyrrole-2-carboxylate (8-1) [0522] To a stirred solution of methyl 3-bromo-1H-pyrrole-2-carboxylate (6-1) (5 g) in DMF were added Cs₂CO₃ (16 g) and [1-(tert-butoxycarbonylamino)cyclobutyl]methyl methanesulfonate (6.8 g) at RT. The RM was heated at 80 °C for 16 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (20% ethyl acetate in hexane) to afford the title compound (8-1). MS (ESI⁺): m/z 387.20 [M (⁷⁹Br)+H]⁺, 389.20 [M (⁸¹Br)+H]⁺. Step-2: methyl 3-bromo-1-((1-((tert-butoxycarbonyl)amino)cyclobutyl)methyl)-4-iodo-1H-pyrrole-2- carboxylate (8-2) [0523] Prepared using a similar method described for the synthesis of (6-3). MS (ESI⁺): m/z 413.03 [M (⁷⁹Br) -100]⁺, 415.03 ([M (⁸¹Br) -100]⁺. Step-3: 8'-bromo-7'-iodo-4'H-spiro[cyclobutane-1,3'-pyrrolo[1,2-a]pyrazin]-1'(2'H)-one (8-3) [0524] Prepared using a similar method described for the synthesis of (Int-1). MS (ESI⁺): m/z 380.85 [M (⁷⁹Br)+H]⁺, 382.85 [M (⁸¹Br)+H]⁺. Step-4:8-bromo-7-iodo-2-[(4-methoxyphenyl)methyl]spiro[4H-pyrrolo[1,2-a]pyrazine-3,1'-cyclobutane]- 1-one (Int-8) [0525] Prepared using a similar method described for the synthesis of (4-1). MS (ESI⁺): m/z 501.15 [M (⁷⁹Br)+H]⁺, 503.15 [M (⁸¹Br)+H]⁺. [0526] The intermediates shown in Table 4 (Int-9 and Int-10) were prepared using similar methods to those described for the synthesis of Int-8 by changing corresponding mesylate derivative (step-1) and the analytical data are described below. [0527] Table 4. Intermediate-9 and Intermediate-10

Intermediate-11: 8'-((3-chloro-2-methylphenyl)amino)-2'-(4-methoxybenzyl)-7'-(thieno[3,2-b]pyridin-7- yl)-4'H-spiro[cyclobutane-1,3'-pyrrolo[1,2-a]pyrazin]-1'(2'H)-one (Int-11)

Step-1: 8'-bromo-2'-(4-methoxybenzyl)-7'-(thieno[3,2-b]pyridin-7-yl)-4'H-spiro[cyclobutane-1,3'- pyrrolo[1,2-a]pyrazin]-1'(2'H)-one (11-1) [0528] To a stirred solution of 8'-bromo-7'-iodo-2'-(4-methoxybenzyl)-4'H-spiro[cyclobutane-1,3'- pyrrolo[1,2-a]pyrazin]-1'(2'H)-one (Int-8) (500 mg) and thieno[3,2-b]pyridin-7-ylboronic acid (357 mg) in 1,4-dioxane: water (4:1 ratio) was added K₂CO₃ (414 mg) at RT. The RM was purged under a stream of argon for 15 min and treated with Pd(dppf)Cl_2.DCM (73 mg). The RM was stirred at 80 °C for 4 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (4% methanol in DCM) to afford the title compound (11-1). MS (ESI⁺): m/z 508.14 [M (⁷⁹Br)+H]⁺, 510.14 [M (⁸¹Br)+H]⁺. Step-2: 8'-((3-chloro-2-methylphenyl)amino)-2'-(4-methoxybenzyl)-7'-(thieno[3,2-b]pyridin-7-yl)-4'H- spiro[cyclobutane-1,3'-pyrrolo[1,2-a]pyrazin]-1'(2'H)-one (Int-11) [0529] Prepared using a similar method described for the synthesis of (Int-6). MS (ESI⁺): m/z 569.18 [M+H]⁺.

[0530] The intermediates listed in Table 5 (Int-12 to Int-15) were prepared using similar methods to those described for the synthesis of Int-11 by changing corresponding boronic acids (step-1) and anilines (step-2). The analytical data are described below. [0531] Table 5. Intermediate-12 to Intermediate-15

Intermediate 16: 7-bromo-6-(hydroxymethyl)-8-iodo-2-(4-methoxybenzyl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Int-16)

Step-1: ethyl 4-bromo-5-methyl-1H-pyrrole-2-carboxylate (16-2) [0532] To a stirred solution of ethyl 5-methyl-1H-pyrrole-2-carboxylate (16-1) (15 g) in DMF was added NBS (17 g) at 0 °C. The RM was stirred at RT for 12 h, diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (20% ethyl acetate in hexane) to afford the title compound (16-2). MS (ESI⁺): m/z 232.08 [M (⁷⁹Br)+H]⁺, 234.08 [M (⁸¹Br)+H]⁺. Step-2: ethyl 4-bromo-3-iodo-5-methyl-1H-pyrrole-2-carboxylate (16-3) [0533] To a stirred solution of ethyl 4-bromo-5-methyl-1H-pyrrole-2-carboxylate (16-2) (20 g) in DMF was added NIS (23 g) at 0 °C. The RM was stirred at RT for 12 h, diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine solution (500 mL), dried over anhydrous Na₂SO_4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (20% ethyl acetate in hexane) to afford the title compound (16-3). MS (ESI⁺): m/z 357.88 [M (⁷⁹Br)+H]⁺, 359.88 [M (⁸¹Br)+H]⁺ Step-3: ethyl 4-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-3-iodo-5-methyl-1H-pyrrole-2- carboxylate (16-4) [0534] Prepared using a similar method described for the synthesis of (1-3). MS (ESI⁺): m/z 501.03 [M (⁷⁹Br)+H]⁺, 503.03 [M (⁸¹Br)+H]⁺. Step-4: 7-bromo-8-iodo-6-methyl-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (16-5) [0535] Prepared using a similar method described for the synthesis of (Int-1). MS (ESI⁺): m/z 354.99 [M (⁷⁹Br)+H]⁺, 356.99 [M (⁸¹Br)+H]⁺. Step-5: 7-bromo-8-iodo-2-(4-methoxybenzyl)-6-methyl-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (16-6) [0536] Prepared using a similar method described for the synthesis of (4-1). MS (ESI⁺): m/z 474.88 [M (⁷⁹Br)+H]⁺, 476.88 [M (⁸¹Br)+H]⁺. Step-6: 7-bromo-8-iodo-2-(4-methoxybenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-6- carbaldehyde (Int-16-7) and 7-bromo-6-(hydroxymethyl)-8-iodo-2-(4-methoxybenzyl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-16) [0537] A solution of 7-bromo-8-iodo-2-(4-methoxybenzyl)-6-methyl-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (16-6) (20 g) in THF: water (1:1 ratio) and acetic acid was treated with CAN (79 g) in several portions at RT. The RM was stirred at RT for 18 h, diluted with ice-cold water and extracted using ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (15% ethyl acetate in hexane) to afford the title compound (16-7). MS (ESI⁺): m/z 488.85 [M (⁷⁹Br)+H]⁺, 490.85 [M (⁸¹Br) +H]⁺ and compound (Int-16). MS (ESI⁺): m/z 490.87 [M (⁷⁹Br)+H]⁺, 492.87 [M (⁸¹Br)+H]⁺. Intermediate 17: 7-bromo-8-iodo-2-(4-methoxybenzyl)-6-(((tetrahydro-2H-pyran-4-yl)oxy)methyl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-17)

Step-1: 7-bromo-6-(chloromethyl)-8-iodo-2-(4-methoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)- one (17-1) [0538] To a stirred solution of 7-bromo-6-(hydroxymethyl)-8-iodo-2-[(4-methoxyphenyl)methyl]- 3,4-dihydropyrrolo [1,2-a]pyrazin-1-one (Int-16) (0.5 g) in DCM was added SOCl₂ (0.4 g) at 0 °C. The RM was stirred at RT for 3 h, cooled to RT, diluted with DCM, and saturated NaHCO₃ solution and extracted with DCM. The organic layer was dried over Na₂SO₄ and evaporated under reduced pressure to obtain the crude product (17-1) (0.5 g), which was used as such in the next step without further purification and characterization. Step-2: 7-bromo-8-iodo-2-(4-methoxybenzyl)-6-(((tetrahydro-2H-pyran-4-yl)oxy)methyl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-17) [0539] NaH (60% in mineral oil) (90 mg) was treated with an ice-cold solution of tetrahydropyran-4- ol (145 mg) in DMF and stirred for 30 min, followed by addition of 7-bromo-6-(chloromethyl)-8-iodo-2- [(4-methoxyphenyl)methyl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one (17-1) (600 mg) in DMF at 0 °C. The RM was stirred at RT for 2 h, diluted with ice-cold water. The resulting solid was collected by filtration, washed with cold water, and dried under vacuum pressure to afford the title compound (Int-17). MS (ESI⁺): m/z 575.23 [M (⁷⁹Br)+H]⁺, 577.23 [M (⁸¹Br)+H]⁺. [0540] The intermediates listed in Table 6 (Int-18 to Int-27) were prepared using similar methods to those described for the synthesis of Int-17 by changing corresponding alcohol and amine (step-2). The analytical data are described below. [0541] Table 6. Intermediate-18 to Intermediate-27

Intermediate 28: 7-bromo-6-((oxetan-3-yloxy)methyl)-8-(phenylamino)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Int-28)

Step-1: 7-bromo-8-iodo-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-6-carbaldehyde (28-1) [0542] Prepared using a similar method described for the synthesis of (Int-16-7 and Int-16). MS (ESI⁺): m/z 368.84 [M (⁷⁹Br)+H]⁺, 370.84 [M (⁸¹Br)+H]⁺. Step-2: 7-bromo-6-(hydroxymethyl)-8-iodo-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (28-2) [0543] To a stirred solution of 7-bromo-8-iodo-1-oxo-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazine-6- carbaldehyde (2 g) in MeOH was added NaBH₄ (0.2 g) in several portions at 0 °C. The RM was stirred at 0 °C for 2 h, diluted with cold water. The solid was collected by filtration, washed with cold water and dried under vacuum to afford the title compound (28-2). MS (ESI⁺): m/z 370.82 [M (⁷⁹Br)+H]⁺, 372.82 [M (⁸¹Br)+H]⁺. Step-3: 7-bromo-6-(chloromethyl)-8-iodo-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (28-3) [0544] Prepared using a similar method described for the synthesis of (17-1), which was used as such in the next step without further purification and characterization. Step-4: 7-bromo-8-iodo-6-((oxetan-3-yloxy)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (28-4) [0545] Prepared using a similar method described for the synthesis of (Int-17). MS (ESI⁺): m/z 427.00 [M (⁷⁹Br)+H]⁺, 429.02 [M (⁸¹Br)+H]⁺. Step-5: 7-bromo-6-((oxetan-3-yloxy)methyl)-8-(phenylamino)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)- one (Int-28) [0546] To a stirred solution of 7-bromo-8-iodo-6-((oxetan-3-yloxy)methyl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (28-5) (400 mg) and aniline (218 mg) in DMF was added Cs₂CO₃ (762 mg) at RT. The RM was purged under a stream of argon for 15 min and treated with xantphos (108 mg) and Pd₂(dba)₃ (85 mg). The RM was heated at 120 °C for 1 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (3% methanol in DCM) to afford the title compound (Int-28). MS (ESI⁺): m/z 392.03 [M (⁷⁹Br)+H]⁺, 394.03 [M (⁸¹Br)+H]⁺. [0547] The intermediate listed in Table 7 (Int-29) was prepared using similar methods to those described for the synthesis of Int-28 by changing corresponding aniline (step-5) and the analytical are described below. [0548] Table 7. Intermediate-29

Intermediate 30: 7-bromo-8-iodo-2-(4-methoxybenzyl)-6-(methoxymethyl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Int-30)

Step-1: 7-bromo-8-iodo-2-(4-methoxybenzyl)-6-(methoxymethyl)-3,4-dihydropyrrolo[1,2-a]pyrazin- 1(2H)-one (Int-30) [0549] NaH (60% in mineral oil) (112mg) was treated with an ice-cold solution of 7-bromo-6- (hydroxymethyl)-8-iodo-2-(4-methoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-16) (600 mg) in THF and stirred for 30 min, followed by addition of MeI (693 mg) in THF at 0 °C. The RM was stirred at RT for 5 h, diluted with ice-cold water and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (50% ethyl acetate in hexane) to afford the title compound (Int-30). MS (ESI⁺): m/z 505.18 [M (⁷⁹Br)+H]⁺, 507.18 [M (⁸¹Br)+H]⁺. [0550] The intermediate listed in Table 8 (Int-31) was prepared using similar methods to those described for the synthesis of Int-30 by changing corresponding halide (step-1) and the analytical data are described below. [0551] Table 8. Intermediate-31

Intermediate 32: 8-((3-chloro-2-methylphenyl)amino)-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-6- (((tetrahydro-2H-pyran-4-yl)oxy)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-32)

Step-1: 7-bromo-8-((3-chloro-2-methylphenyl)amino)-2-(4-methoxybenzyl)-6-(((tetrahydro-2H-pyran-4- yl)oxy)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (32-1) [0552] Prepared using a similar method described for the synthesis of (Int-4). MS (ESI⁺): m/z 588.25 [M (⁷⁹Br)+H]⁺, 590.30 [M (⁸¹Br)+H]⁺. Step-2: 8-((3-chloro-2-methylphenyl)amino)-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-6-(((tetrahydro-2H- pyran-4-yl)oxy)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-32) [0553] To a stirred solution of 7-bromo-8-((3-chloro-2-methylphenyl)amino)-2-(4-methoxybenzyl)- 6-(((tetrahydro-2H-pyran-4-yl)oxy)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (32-1) (380 mg) in 1,4-dioxane: water (4:1 ratio) was added K₃PO₄ (410 mg) and 4-pyridylboronic acid (95 mg) at RT. The RM was purged under a stream of argon for 15 min and treated with X-PhosPdG₂ (50 mg). The RM was then stirred at 100 °C for 3 h, cooled to ambient temperature, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (1% methanol in DCM) to afford the title compound (Int-32). MS (ESI⁺): m/z 587.17 [M+H]⁺.

[0554] The intermediates listed in Table 9 (Int-33 to Int-47) were prepared using similar methods to those described for the synthesis of Int-32 by changing corresponding anilines (step-1) and boronic acids (step-2). The analytical data are described below. [0555] Table 9. Intermediate-33 to Intermediate-47

Intermediate 48: 8-((3-chloro-2-methylphenyl)amino)-2-(4-methoxybenzyl)-6-(((1-methyl-1H-pyrazol-3- yl)oxy)methyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-48)

Step-1: 7-bromo-8-((3-chloro-2-methylphenyl)amino)-6-(hydroxymethyl)-2-(4-methoxybenzyl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (48-1) [0556] Prepared using a similar method described for the synthesis of (Int-28). MS (ESI⁺): m/z 504.15 [M (⁷⁹Br)+H]⁺, 506.15 [M (⁸¹Br)+H]⁺. Step-2: 8-((3-chloro-2-methylphenyl)amino)-6-(hydroxymethyl)-2-(4-methoxybenzyl)-7-(pyridin-4-yl)- 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (48-2) [0557] Prepared using a similar method described for the synthesis of (Int-32). MS (ESI⁺): m/z 503.16 [M+H]⁺. Step-3: 8-((3-chloro-2-methylphenyl)amino)-2-(4-methoxybenzyl)-6-(((1-methyl-1H-pyrazol-3- yl)oxy)methyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-48) [0558] A mixture of 8-(3-chloro-2-methyl-anilino)-6-(hydroxymethyl)-2-[(4- methoxyphenyl)methyl]-7-(4-pyridyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one (100 mg) (48-2), 1- methylpyrazol-3-ol (29 mg) and PPh₃ (97 mg) in toluene was treated with DIAD (60 mg) at RT. The RM was stirred for 2 h, diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (20% ethyl acetate in hexane) to afford the title compound (Int-48). MS (ESI⁺): m/z 583.15 [M+H]⁺. [0559] The intermediate listed in Table 10 (Int-49 and Int-50) were prepared using similar methods to those described for the synthesis of Int-48 by changing corresponding aniline (step-1) and corresponding alcohol (step-3). The analytical data are described below. [0560] Table 10. Intermediate-49 and Intermediate-50

Step-1: 8-chloro-6-iodo-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (51-1) [0561] To a stirred solution of 8-chloro-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-1) (3 g) in DMF was added NIS (2.7 g) at RT. The RM was heated at 80 °C for 24 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (3% methanol in DCM) to afford the title compound (51-1).¹H NMR (400 MHz, DMSO-d6): δ 8.66 (d, J = 4.8 Hz, 2H), 7.99 (s, 1H), 7.41 (m, 2H), 4.09 (t, J = 11.6 Hz, 2H), 3.54 (t, J = 11.2, 2H). Step-2: 8-chloro-6-iodo-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)- one (Int-51) [0562] Prepared using a similar method described for the synthesis of (4-1). MS (ESI⁺): m/z 494.19 [M+H]⁺. Intermediate 52: 7-bromo-8-chloro-2-(4-methoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-52)

Step-1: methyl 1-(2-aminoethyl)-4-bromo-3-chloro-1H-pyrrole-2-carboxylate (52-1) [0563] Prepared using a similar method described for the synthesis of (Int-1). MS (ESI⁺): m/z 248.94 [M (⁷⁹Br)+H]⁺, 250.94 [M (⁸¹Br)+H]⁺. Step-3:7-bromo-8-chloro-2-(4-methoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-52) [0564] Prepared using a similar method described for the synthesis of (4-1). MS (ESI⁺): m/z 369.17 [M (⁷⁹Br)+H]⁺, 371.17 [M (⁸¹Br)+H]⁺.

Intermediate-53: 2-(4-methoxybenzyl)-8-(phenylamino)-7-(thieno[2,3-d]pyrimidin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-53)

Step-1: 8-chloro-2-(4-methoxybenzyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (53-1) [0565] To a stirred solution of 7-bromo-8-chloro-2-(4-methoxybenzyl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Int-52) (1 g) and bispin (0.7 g) in dioxane was added KOAc (0.8 g) at RT. The RM was purged under a stream of argon for 15 min and treated with Xphos (0.3 g) and Pd₂(dba)₃ (0.3 g). The RM was heated at 100 °C for 2 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure to afford the crude title compound (53-1), which was used for next step without purification and characterization. Step-2: 8-chloro-2-(4-methoxybenzyl)-7-(thieno[2,3-d]pyrimidin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin- 1(2H)-one (53-2) [0566] To a stirred solution of 8-chloro-2-(4-methoxybenzyl)-7-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (53-1) (1.1 g) and 4-chlorothieno[2,3- d]pyrimidine (0.4 g) in 1,4-dioxane: water (4:1 ratio) was added K₂CO₃ (0.8 g) at RT. The RM was purged under a stream of argon for 15 min and treated with tetrakis Pd(0) (0.3 g). The RM was stirred at 110 °C for 1 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (6% methanol in DCM) to afford the title compound (53-2). MS (ESI⁺): m/z 425.11 [M+H]⁺. Step-3: 2-(4-methoxybenzyl)-8-(phenylamino)-7-(thieno[2,3-d]pyrimidin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Int-53) [0567] To a stirred solution of 8-chloro-2-(4-methoxybenzyl)-7-(thieno[2,3-d]pyrimidin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (53-2) (200 mg) and aniline (219 mg) in DMF was added Cs₂CO₃ (383 mg) at RT, purged under stream of argon for 15 min and treated with EPhos PdG₄ (216 mg) and EPhos (251 mg). The RM was stirred at 80 °C for 4 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (80% ethyl acetate in hexane) to afford the title compound (Int-53). MS (ESI⁺): m/z 482.25 [M+H]⁺. [0568] The intermediate listed in Table 11 (Int-54 to Int-58) were prepared using similar methods to those described for the synthesis of Int-53 by changing corresponding halide (step-2) and corresponding aniline (step-3). The analytical data are described below. [0569] Table 11. Intermediate-54 to Intermediate-58

Intermediate-59: 2-(4-methoxybenzyl)-8-(phenylamino)-7-(pyridazin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Int-59)

Step-1: 8-chloro-2-(4-methoxybenzyl)-7-(pyridazin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (59-1) [0570] Prepared using a similar method described for the synthesis of (Int-32). MS (ESI⁺): m/z 369.17 [M+H]⁺. Step-2: 2-(4-methoxybenzyl)-8-(phenylamino)-7-(pyridazin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin- 1(2H)-one (Int-59) [0571] Prepared using a similar method described for the synthesis of (Int-53). MS (ESI⁺): m/z 426.31 [M+H]⁺. Intermediate 60: 8'-bromo-7'-(pyridin-4-yl)-4'H-spiro[oxetane-3,3'-pyrrolo[1,2-a]pyrazin]-1'(2'H)-one (Int-60)

Step-1: methyl 3-bromo-1-((3-((tert-butoxycarbonyl)amino)oxetan-3-yl)methyl)-1H-pyrrole-2- carboxylate (60-1) [0572] Prepared using a similar method described for the synthesis of (8-1). MS (ESI⁺): m/z 333.02 [M (⁷⁹Br)–56] ⁺, 335.02 [M (⁸¹Br)–56]⁺. Step-2: methyl 3-bromo-1-((3-((tert-butoxycarbonyl)amino)oxetan-3-yl)methyl)-4-iodo-1H-pyrrole-2- carboxylate (60-2) [0573] Prepared using a similar method described for the synthesis of (6-3). MS (ESI⁺): m/z 512.96 [M (⁷⁹Br)–H]⁺, 515.00 [M (⁸¹Br)–H]⁺. Step-3: methyl 3-bromo-1-((3-((tert-butoxycarbonyl)amino)oxetan-3-yl)methyl)-4-(pyridin-4-yl)-1H- pyrrole-2-carboxylate (60-3) [0574] Prepared using a similar method described for the synthesis of (1-4). MS (ESI⁺): m/z 466.04 [M (⁷⁹Br)+H] ⁺, 468.04 [M (⁸¹Br)+H] ⁺. Step-4: methyl 1-((3-aminooxetan-3-yl)methyl)-3-bromo-4-(pyridin-4-yl)-1H-pyrrole-2-carboxylate (60-4) [0575] To an ice cold solution of methyl 3-bromo-1-((3-((tert-butoxycarbonyl)amino)oxetan-3- yl)methyl)-4-(pyridin-4-yl)-1H-pyrrole-2-carboxylate (60-3) (0.45 g) in DCM was added TFA (1.1 g). The RM was stirred at RT for 6 h, basified with saturated NaHCO₃ solution (~pH 7-8) and extracted with DCM. The combined organic layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound (60-4), which was used in the next step without further purification and characterization. Step-5: 8'-bromo-7'-(pyridin-4-yl)-4'H-spiro[oxetane-3,3'-pyrrolo[1,2-a]pyrazin]-1'(2'H)-one (Int-60) [0576] To a stirred solution of methyl 1-((3-aminooxetan-3-yl)methyl)-3-bromo-4-(pyridin-4-yl)- 1H-pyrrole-2-carboxylate (60-4) (0.3 g) in MeOH was added K₂CO₃ (0.3 g) followed by addition of TEA (0.2 g) at 0 °C. The RM was stirred at RT for 6 h, concentrated under reduce pressure, diluted with water, and extracted with DCM. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (5% methanol in DCM) to afford the title compound (Int-60). MS (ESI⁺): m/z 334.08 [M (⁷⁹Br)+H]⁺, 336.08 [M (⁸¹Br)+H]⁺. Intermediate 61: 8-bromo-3,3-dimethyl-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-61)

Step-1: methyl 3-bromo-1-(2-((tert-butoxycarbonyl)amino)-2-methylpropyl)-1H-pyrrole-2-carboxylate (61-1) [0577] To a stirred solution of tert-butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2- dioxide (3.5 g) in 1,4-dioxane were added methyl 3-bromo-1H-pyrrole-2-carboxylate (6-1) (2.3 g), K₂CO₃ (13 g) and 18-crown-6 (0.7 g) at RT. The RM was heated at 100 °C for 12 h, cooled to RT, diluted with water, and extracted using ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (30% ethyl acetate in hexane) to afford the title compound (61-1). MS (ESI⁺): m/z 275.00 [M (⁷⁹Br) –100]⁺, 276.96 ([M (⁸¹Br) –100]⁺. Step-2 methyl 3-bromo-1-(2-((tert-butoxycarbonyl)amino)-2-methylpropyl)-4-iodo-1H-pyrrole-2- carboxylate (61-2) [0578] Prepared using a similar method described for the synthesis of (6-3). MS (ESI⁺): m/z 500.90 [M (⁷⁹Br)+H]⁺, 502.90 [M (⁸¹Br)+H]⁺. Step-3: methyl 3-bromo-1-(2-((tert-butoxycarbonyl)amino)-2-methylpropyl)-4-(pyridin-4-yl)-1H-pyrrole- 2-carboxylate (61-3) [0579] Prepared using a similar method described for the synthesis of (1-4). MS (ESI⁺): m/z 452.07 [M (⁷⁹Br)+H]⁺, 454.10 [M (⁸¹Br)+H]⁺. Step-4: 8-bromo-3,3-dimethyl-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-61) [0580] Prepared using a similar method described for the synthesis of (Int-1). MS (ESI⁺): m/z 320.00 [M (⁷⁹Br)+H]⁺, 321.99 [M (⁸¹Br)+H]⁺. Intermediate-62: 2-ethyl-3-fluoroaniline (Int-62)

Step-1: 1-fluoro-3-nitro-2-vinylbenzene (62-2) [0581] To a stirred solution of 2-bromo-1-fluoro-3-nitro-benzene (2 g) (62-1) in 1,4-dioxane was added K₂CO₃ (2.5 g) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (2.1 g) at RT. The RM was purged under a stream of argon for 15 min and treated with PdCl₂(dppf).DCM (0.7 g). The RM was stirred at 90 °C for 12 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (0.7% methanol in DCM) to afford the title compound (62-2).1H NMR (400 MHz, DMSO-d6): δ 7.84 (dd, J = 8.1, 1.3 Hz, 1H), 7.68 – 7.57 (m, 1H), 6.71 – 6.64 (m, 1H), 5.78 (s, 1H), 5.74 (dt, J = 11.7, 1.4 Hz, 2H). Step-2: 2-ethyl-3-fluoroaniline (Int-62) [0582] To a stirred solution of 1-fluoro-3-nitro-2-vinylbenzene (300 mg) in methanol was added 10% Pd/C (180 mg) at RT under N₂ atmosphere. The RM was stirred under H₂ atmosphere (balloon pressure) at RT for 3 h. The RM was filtered through celite bed and washed with 10% methanol in DCM solution, concentrated under reduced pressure to afford the title compound (Int-62). MS (ESI⁺): m/z 139.97 [M+H]⁺. Intermediate-63: 4-bromo-3-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridine (Int-63)

Step-1: 3-ethynyl-1-methyl-1H-pyrazole (63-2) [0583] To a stirred solution of 1-methyl-1H-pyrazole-3-carbaldehyde (5 g) in methanol was added CS₂CO₃ (22 g) at RT. The RM was cooled to 0 °C, treated with 1-diazo-1-dimethoxyphosphoryl- propan-2-one (13 g), stirred at RT for 48 h, concentrated under reduced pressure, diluted with water, and extracted with DCM. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (2% methanol in DCM) to afford the title compound (63-2). MS (ESI⁺): m/z 107.01 [M+H]⁺. Step-2: 4-bromo-3-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridine (Int-63) [0584] To a stirred solution of 4-bromo-3-iodo-pyridine (1.0 g) in ACN were added TEA (1.0 g) and dikis (0.5 g) at RT and stirred for 10 min. followed by the addition of 3-ethynyl-1-methyl-pyrazole (63-2) (0.4 g) and CuI (0.1 g) at RT and stirred for 2 h. The RM was filtered through celite bed, washed with ACN, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (2% methanol in DCM) to afford the compound (Int-63). MS (ESI⁺): m/z 261.95 [M (⁷⁹Br)+H]⁺, 263.95 [M (⁸¹Br)+H]⁺.

[0585] The intermediate listed in Table 12 (Int-64) was prepared using similar methods to those described for the synthesis of Int-63 by changing corresponding aldehyde (step-1) and the analytical data are described below. [0586] Table 12. Intermediate-64

IV. EXAMPLE COMPOUNDS Example 1: 8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

[0587] To a stirred solution of 8-chloro-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-1) (120 mg) and aniline (180 mg) in DMF (1.2 mL) was added CS₂CO₃ (473 mg) at RT. The RM was purged under stream of argon for 15 min and treated with xantphos (56 mg) and Pd₂(dba)₃ (44 mg) at RT. The RM was stirred at 150 °C for 2 h in microwave, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (3% methanol in DCM) to afford the title compound (Example-1). MS (ESI⁺): m/z 305.34 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.31 (s, 2H), 7.79 (s, 1H), 7.63 (d, J = 12.2 Hz, 2H), 7.42 (s, 2H), 7.02 (appt, J = 7.1 Hz, 2H), 6.63 – 6.61 (m, 3H), 4.12 (s, 2H), 3.51 (s, 2H). [0588] Following compounds listed in Table 13 (Examples 2–18) were prepared using similar methods to those described for the synthesis of Example 1 and the analytical data are described below. [0589] Table 13. Examples 2-18

Example 19: 8-((2,3-difluorophenyl)amino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)- one

[0590] To a stirred solution of 8-((2,3-difluorophenyl)amino)-2-(4-methoxybenzyl)-7-(pyridin-4-yl)- 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-4) (150 mg) in DCM was added triflic acid (146 mg) at 0 ^oC. The RM was stirred at RT for 2 h, diluted with saturated NaHCO₃ and extracted using DCM. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (2.5% methanol in DCM) to afford the title compound (Ex.19). MS (ESI⁺): m/z 341.28 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.39 (dd, J = 1.6, 4.8 Hz, 2H), 7.83 (s, 1H), 7.67 (s, 1H), 7.65 (s, 1H), 7.43 (dd, J = 4.8, 1.6 Hz, 2H), 6.75 – 6.60 (m, 2H), 6.18 (appt, J = 8.0 Hz, 1H), 4.16 (t, J = 5.6 Hz, 2H), 3.54 (s, 2H). [0591] The following compound shown in Table 14 (Examples 20–51) were prepared using similar methods to those described for the synthesis of Example 19 and the analytical data are described below. [0592] Table 14. Example 20-51

Example 52: (3aS,9aR)-6-((2,3-difluorophenyl)amino)-7-(3-fluoropyridin-4-yl)-1,2,3,3a,4,9a-hexahydro- 5H-cyclopenta[e]pyrrolo[1,2-a]pyrazin-5-one and Example 53: (3aR,9aS)-6-((2,3-difluorophenyl)amino)-7-(3-fluoropyridin-4-yl)-1,2,3,3a,4,9a-hexahydro- 5H-cyclopenta[e]pyrrolo[1,2-a]pyrazin-5-one

[0593] Prepared using a similar method described for the synthesis of (Ex.19). [0594] MS (ESI⁺): m/z 399.33 [M+H]⁺. The racemic mixture was purified by SFC to afford the title compound (Ex.52 and Ex.53). [0595] Example 52: (arbitrarily assigned stereochemistry) MS (ESI⁺): m/z 399.37 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ.8.47 (s, 1H), 8.35 (s, 1H), 8.22 (d, J = 5.1 Hz, 1H), 7.88 (s, 1H), 7.48 (s, 1H), 7.41 (s, 1H), 6.69 – 6.67 (m, 2H), 6.18 (d, J = 7.9 Hz, 1H), 3.92 – 3.90 (m, 1H), 3.57 (s, 1H), 2.39 – 2.38 (m, 1H), 1.95 (s, 3H), 1.81 – 1.79 (m, 1H), 1.58 (s, 1H). [0596] Example 53: (arbitrarily assigned stereochemistry) MS (ESI⁺): m/z 399.09 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ.8.48 (d, J = 2.7 Hz, 1H), 8.36 (s, 1H), 8.23 (d, J = 5.0 Hz, 1H), 7.89 (s, 1H), 7.51 (dd, J = 6.7, 5.0 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 6.71 – 6.64 (m, 2H), 6.21 (appt, J = 7.8 Hz, 1H), 3.92 – 3.90 (m, 1H), 3.59 – 3.58 (m, 1H), 2.39 – 2.38 (m, 1H), 1.96 (s, 3H), 1.82 – 1.79 (m, 1H), 1.59 (s, 1H).

Example 54: (R)-8-((3-chloro-2-methylphenyl)amino)-6-((3-methoxypyrrolidin-1-yl)methyl)-7-(pyridin-4- yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one and Example 55: (S)-8-((3-chloro-2-methylphenyl)amino)-6-((3-methoxypyrrolidin-1-yl)methyl)-7-(pyridin-4- yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

[0597] The racemic Int-33 was purified by SFC to afford the title compound (33-1 and 33-2). Prepared using a similar method described for the synthesis of (Ex.19). [0598] (33-1), MS (ESI⁺): m/z 586.40 [M+H]⁺ (33-2), MS (ESI⁺): m/z 586.19 [M+H]⁺. [0599] Example 54: (arbitrarily assigned stereochemistry) MS (ESI⁺): m/z 466.20 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ.8.36 (d, J = 5.1 Hz, 2H), 7.81 (s, 1H), 7.45 (s, 1H), 7.31 (d, J = 4.4 Hz, 2H), 6.68 – 6.60 (m, 2H), 6.25 (d, J = 7.8 Hz, 1H), 4.14 (s, 2H), 3.82 (s, 1H), 3.66 (s, 2H), 3.52 (s, 3H), 3.11 (s, 3H), 2.69 – 2.55 (m, 2H), 2.29 (s, 3H), 1.95 – 1.90 (m, 1H), 1.60 (s, 1H), 1.24 (s, 1H). [0600] Example 55: (arbitrarily assigned stereochemistry) MS (ESI⁺): m/z 466.38 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.37 (d, J = 5.1 Hz, 2H), 7.80 (s, 1H), 7.45 (s, 1H), 7.31 (d, J = 5.0 Hz, 2H), 6.68 – 6.60 (m, 2H), 6.26 (d, J = 7.8 Hz, 1H), 4.14 (s, 2H), 3.82 (s, 1H), 3.66 (s, 2H), 3.53 (s, 3H), 3.11 (s, 3H), 2.61 - 2.57 (m, 2H), 2.22 (s, 3H), 1.95 – 1.90 (m, 1H), 1.62 (d, J = 10.5 Hz, 1H), 1.24 (s, 1H). Example 56: 6-((oxetan-3-yloxy)methyl)-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one

[0601] Prepared using a similar method described for the synthesis of (Int-32). [0602] MS (ESI⁺): m/z 391.18 [M+H]⁺.¹H NMR (400 MHz, DMSO-d6): δ 8.41 (d, J = 5.1 Hz, 2H), 7.84 (s, 1H), 7.56 (s, 1H), 7.30 (d, J = 5.1 Hz, 2H), 6.92 (appt, J = 7.7 Hz, 2H), 6.54 – 6.52 (m, 3H), 4.58 (s, 3H), 4.44 (s, 2H), 4.40 (s, 2H), 4.14 (s, 2H), 3.55 (s, 2H). [0603] The following compound listed in Table 15 (Example 57) was prepared using similar methods to those described for the synthesis of Example 56 and the analytical data are described below. [0604] Table 15. Example 57

Example 58: 7-(pyridin-4-yl)-8-(quinolin-8-ylamino)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

[0605] Prepared using a similar method described for the synthesis of (Ex.1). MS (ESI⁺): m/z 356.21 [M+H]⁺.¹H NMR (400 MHz, DMSO-d6): δ 8.95 (s, 1H), 8.90 (dd, J = 4.2, 1.7 Hz, 1H), 8.32 (d, J = 6.2 Hz, 1H), 8.28 (dd, J = 8.3, 1.7 Hz, 2H), 7.78 (s, 1H), 7.70 (s, 1H), 7.59 (dd, J = 8.3, 4.2 Hz, 1H), 7.40 (appt, J = 4.8 Hz, 2H), 7.20 (d, J = 7.6 Hz, 1H), 7.11 (appt, J = 7.9 Hz, 1H), 6.37 (d, J = 7.6 Hz, 1H), 4.18 (t, J = 5.2 Hz, 2H), 3.53 (s, 2H). [0606] The following compounds listed in Table 16 (Example 59–61) were prepared using similar methods to those described for the synthesis of Example 58 and the analytical data are described below. [0607] Table 16. Example 59-61

Example 62: 6-(1-methyl-1H-pyrazol-3-yl)-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one

Step-1: 8-chloro-6-(1-methyl-1H-pyrazol-3-yl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)- one (62-3) [0608] To a stirred solution of 8-chloro-6-iodo-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin- 1(2H)-one (51-1) (350 mg) and 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (292 mg) in 1,4-dioxane: water (4:1 ratio) was added K2CO3 (258 mg) at RT. The RM was purged under a stream of argon for 10 min and treated with Pd(dppf)Cl2 (76 mg) at RT. The RM was stirred at 80 °C for 24 h, cooled to RT, diluted with water (100 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (5% methanol in DCM) to afford the title compound (62-3). MS (ESI⁺): m/z 328.25 [M+H]⁺ . Step-2: 8-chloro-2-(4-methoxybenzyl)-6-(1-methyl-1H-pyrazol-3-yl)-7-(pyridin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (62-4) [0609] Prepared using a similar method described for the synthesis of (4-1). MS (ESI⁺): m/z 448.43 [M+H]⁺ . Step-3: 6-(1-methyl-1H-pyrazol-3-yl)-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (62-5) [0610] Prepared using a similar method described for the synthesis of (Ex.1). MS (ESI⁺): m/z 505.18 [M+H]⁺ . Step-4: 6-(1-methyl-1H-pyrazol-3-yl)-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Example-62) [0611] Prepared using a similar method described for the synthesis of (Ex.19). MS (ESI⁺): m/z 385.12 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.25 (s, 2H), 7.80 (s, 1H), 7.75 (d, J = 2.3 Hz, 1H), 7.55 (s, 1H), 7.17 (d, J = 5.1 Hz, 2H), 6.93 (appt, J = 7.7 Hz, 2H), 6.57 – 6.53 (m, 3H), 6.10 (d, J = 2.3 Hz, 1H), 4.11 (t, J = 5.2 Hz, 2H), 3.89 (s, 3H), 3.50 (s, 2H). Example 63: 1-oxo-8-(phenylamino)-7-(pyridin-4-yl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-6- carbonitrile

Step-1: 8-chloro-2-(4-methoxybenzyl)-1-oxo-7-(pyridin-4-yl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-6- carbonitrile (63-3) [0612] To a stirred solution of 8-chloro-6-iodo-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-51) (250 mg) in DMF was added CuCN (113 mg) at RT. The RM was stirred at 150 °C for 24 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (1.5% methanol in DCM) to afford the title compound (63-3). MS (ESI⁺): m/z 393.20 [M+H]⁺. Step-2: 2-(4-methoxybenzyl)-1-oxo-8-(phenylamino)-7-(pyridin-4-yl)-1,2,3,4-tetrahydropyrrolo[1,2- a]pyrazine-6-carbonitrile (63-4) [0613] To a stirred solution of 8-chloro-2-(4-methoxybenzyl)-1-oxo-7-(pyridin-4-yl)-1,2,3,4- tetrahydropyrrolo[1,2-a]pyrazine-6-carbonitrile (63-3) (60 mg) in toluene was added aniline (42 mg) and NaOtBu (15 mg) at RT. The RM was purged under a stream of argon for 10 min before the addition of davephos (30 mg) and Pd₂(dba)₃ (30 mg) at RT. The RM was heated at 110 °C for 36 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (5% methanol in DCM) to afford the title compound (63-4). MS (ESI⁺): m/z 450.50 [M+H]⁺. Step-3: 1-oxo-8-(phenylamino)-7-(pyridin-4-yl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-6-carbonitrile (Example 63) [0614] Prepared using a similar method described for the synthesis of (Ex.19). MS (ESI⁺): m/z 330.25 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.50 (d, J = 5.3 Hz, 2H), 8.20 (s, 1H), 7.68 (s, 1H), 7.44 (d, J = 6.0 Hz, 2H), 6.97 (appt, J = 7.6 Hz, 2H), 6.61 – 6.56 (m, 3H), 4.29 (t, J = 5.9 Hz, 2H), 3.62 (s, 2H). Example 64: 7-(3-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)-8-(phenylamino)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

Step-1: 8-chloro-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin- 1(2H)-one (64-1) [0615] Prepared using a similar method described for the synthesis of (53-1). The obtained crude was used as such in the next step without further purification and characterization. Step-2: 8-chloro-7-(3-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (64-2) [0616] Prepared using a similar method described for the synthesis of (1-4). MS (ESI⁺): m/z 352.22 [M+H]⁺. Step-3: 7-(3-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)-8-(phenylamino)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Example 64) [0617] To a stirred solution of 8-chloro-7-(3-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (64-2) (80 mg) in 1,4-dioxane: water (7:3 ratio) was added aniline (63 mg) and Cs₂CO₃ (148 mg) at RT. The RM was purged under a stream of argon for 15 min and treated with brettphos (12 mg) and Pd₂(dba)₃ (21 mg). The RM was heated at 110 °C for 24 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (3.4 % methanol in DCM) to afford the title compound (Example 64). MS (ESI⁺): m/z 409.38 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.94 (s, 1H), 8.52 (d, J = 5.4 Hz, 1H), 8.37 (s, 1H), 8.16 (d, J = 5.4 Hz, 1H), 7.85 (s, 1H), 7.54 (s, 1H), 7.50 (d, J = 2.0 Hz, 1H), 7.01 (appt, J = 7.7 Hz, 2H), 6.63 (appt, J = 7.3 Hz, 1H), 6.44 (d, J = 7.9 Hz, 2H), 6.09 (d, J = 2.2 Hz, 1H), 4.42 (d, J = 4.4 Hz, 2H), 3.78 (s, 3H), 3.56 (s, 2H). [0618] The following compound shown in Table 17 (Example 65) was prepared using similar methods to those described for the synthesis of Example 64 and the analytical data are described below. [0619] Table 17. Example 65

Example 66: 2-methyl-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

Step-1: 8-chloro-2-methyl-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (66-1) [0620] NaH (60% in mineral oil) (29 mg) was treated with an ice-cold solution of 8-chloro-7- (pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-1) (200 mg) in DMF (2 mL) and stirred for 30 min, followed by addition of MeI (229 mg) in DMF (1 mL) at 0 °C. The RM was stirred at RT for 5 h, diluted with ice-cold water and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (5% methanol in DCM) to afford the title compound (66-1). MS (ESI⁺): m/z 262.20 [M+H]⁺. Step-2: 2-methyl-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Example 66) [0621] To a stirred solution of 8-chloro-2-methyl-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin- 1(2H)-one (130 mg) and aniline (138 mg) in DMF was added K3PO4 (316 mg) at RT. The RM was purged under a stream of argon for 15 min and treated with tBuXPhos PdG₃ (39 mg). The RM was stirred at 150°C for 2 h in microwave, cooled to RT, quenched with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (5% methanol in DCM) to afford the title compound (Ex.66). MS (ESI⁺): m/z 319.33 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.32 (d, J = 6.0 Hz, 2H), 7.64 (s, 1H), 7.60 (s, 1H), 7.42 (d, J = 6.0 Hz, 2H), 7.02 (appt, J = 7.8 Hz, 2H), 6.65 – 6.60 (m, 3H), 4.20 (t, J = 5.6 Hz, 2H), 3.66 (t, J = 5.6 Hz, 2H), 2.94 (s, 3H).

Example 67: 6-methyl-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

Step-1: 8-chloro-6-methyl-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (67-1) [0622] To a stirred solution of 8-chloro-6-iodo-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin- 1(2H)-one (Int- 51) (500 mg) and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (672 mg) in 1,4-dioxane: water (7:3 ratio) was added K2CO3 (369 mg) at RT. The RM was purged under a stream of argon for 10 min and treated with Pd(dppf)Cl2 (109 mg). The RM was stirred at 80 °C for 24 h, cooled to RT, quenched with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (2.5% methanol in DCM) to afford the title compound (67-1). MS (ESI⁺): m/z 262.21 [M+H]⁺ . Step-2: 6-methyl-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Example-67) [0623] Prepared using a similar method described for the synthesis of (Int-28). MS (ESI⁺): m/z 319.36 [M+H]⁺ ; ¹H NMR (400 MHz, DMSO-d6): δ 8.35 (d, J = 6.0 Hz, 2H), 7.64 (s, 1H), 7.59 (s, 1H), 7.21 (d, J = 6.0 Hz, 2H), 6.89 (appt, J = 7.7 Hz, 2H), 6.55 – 6.53 (m, 3H), 4.02 (s, 2H), 3.50 (s, 2H), 2.31 (s, 3H).

Example 68: 8-(phenylamino)-7-(pyridin-4-yl)-6-((2,2,2-trifluoroethoxy)methyl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one

Step-1: 2-(4-methoxybenzyl)-8-(phenylamino)-7-(pyridin-4-yl)-6-((2,2,2-trifluoroethoxy)methyl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (68-1) [0624] To a stirred solution of 6-(hydroxymethyl)-2-(4-methoxybenzyl)-8-(phenylamino)-7-(pyridin- 4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Int-16) (120 mg) and 2,2,2-trifluoroethan-1-ol (79 mg) in toluene was added Tsunoda reagent (191 mg) at RT. The RM was heated at 100°C for 24 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (5% methanol in DCM) to afford the title compound (Ex.68). MS (ESI⁺): m/z 537.33 [M+H]⁺. Step-2: 8-(phenylamino)-7-(pyridin-4-yl)-6-((2,2,2-trifluoroethoxy)methyl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Example 68) [0625] Prepared using a similar method described for the synthesis of (Ex.19). MS (ESI⁺): m/z 417.05 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.40 (d, J = 5.0 Hz, 2H), 7.86 (s, 1H), 7.56 (s, 1H), 7.29 (d, J = 5.0 Hz, 2H), 6.92 (appt, J = 7.6 Hz, 2H), 6.54 – 6.52 (m, 3H), 4.66 (s, 2H), 4.17 – 4.12 (m, 6H).

Example 69: 6-chloro-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

Step-1: 8-bromo-6-chloro-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (69-1) [0626] To a stirred solution of 8-bromo-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)- one (6-5) (0.5 g) in DMF was added NCS (0.5 g) at 0 °C. The RM was stirred at RT for 12 h, diluted with ice-cold water. The resulting precipitate was collected by filtration, washed with saturated aqueous NaHCO₃ solution, sodium thiosulphate solution and dried under vacuum to afford the title compound (69- 1). MS (ESI⁺): m/z 326.11 [M (⁷⁹Br)+H]⁺, 328.11 [M (⁸¹Br)+H]⁺. Step-2: 6-chloro-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Example 69) [0627] Prepared using a similar method described for the synthesis of (Int-4). MS (ESI⁺): m/z 339.03 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.41 (d, J = 5.3 Hz, 2H), 7.86 (s, 1H), 7.68 (s, 1H), 7.39 (d, J = 5.2 Hz, 2H), 6.94 (appt, J = 7.7 Hz, 2H), 6.59 (d, J = 7.7 Hz, 3H), 4.11 (t, J = 5.9 Hz, 2H), 3.56 (s, 2H).

Example 70: 6-(2-methoxyethyl)-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin- 1(2H)-one

Step-1: (E)-7-bromo-8-iodo-2-(4-methoxybenzyl)-6-(2-methoxyvinyl)-3,4-dihydropyrrolo[1,2-a]pyrazin- 1(2H)-one (70-1) [0628] To a stirred solution of Ph₃P(Cl)CH₂OCH₃ (0.8 g) in THF was added KOtBu (0.3 g) at –78 °C. The RM was stirred for 15 min at RT, followed by the addition of 7-bromo-8-iodo-2-(4- methoxybenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-6-carbaldehyde (1 g). The RM was slowly allowed to warm to RT and stirred for 12 h, diluted with water and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (2.5% methanol in DCM) to afford the title compound (70-1). MS (ESI⁺): m/z 516.67 [M (⁷⁹Br)+H]⁺, 518.67 [M (⁸¹Br)+H]⁺. Step-2: (E)-7-bromo-2-(4-methoxybenzyl)-6-(2-methoxyvinyl)-8-(phenylamino)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (70-2) [0629] Prepared using a similar method described for the synthesis of (Int-4). MS (ESI⁺): m/z 482.15 [M (⁷⁹Br)+H]⁺, 484.15 [M (⁸¹Br)+H]⁺. Step-3: (E)-2-(4-methoxybenzyl)-6-(2-methoxyvinyl)-8-(phenylamino)-7-(pyridin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (70-3) [0630] Prepared using a similar method described for the synthesis of (1-4). MS (ESI⁺): m/z 481.30 [M+H]⁺. Step-4: 2-(4-methoxybenzyl)-6-(2-methoxyethyl)-8-(phenylamino)-7-(pyridin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (70-4) [0631] Prepared using a similar method described for the synthesis of (Int-62). MS (ESI⁺): m/z 483.36 [M+H]⁺. Step-5: 6-(2-methoxyethyl)-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)- one (Example 70) [0632] Prepared using a similar method described for the synthesis of (Ex.19). MS (ESI⁺): m/z 363.28 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.62 (s, 2H), 8.34 (s, 1H), 7.43 (s, 3H), 7.34 (appt, J = 7.6 Hz, 1H), 7.28 (s, 1H), 7.20 (d, J = 7.6 Hz, 1H), 6.94 (appt, J = 7.4 Hz, 1H), 6.13 (s, 1H), 3.89 (s, 2H), 3.55 (t, J = 6.0 Hz, 2H), 3.39 (s, 2H), 3.25 (s, 3H), 2.81 (t, J = 6.6 Hz, 2H). Example 71: 7-(3-fluoropyridin-4-yl)-8-(phenylamino)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

Step-1: 8-chloro-7-(3-fluoropyridin-4-yl)-2-(4-methoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)- one (71-1) [0633] Prepared using a similar method described for the synthesis of (Int-32). MS (ESI⁺): m/z 386.09 [M+H]⁺. Step-2: 7-(3-fluoropyridin-4-yl)-2-(4-methoxybenzyl)-8-(phenylamino)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (71-2) [0634] Prepared using a similar method described for the synthesis of (Int-53).MS (ESI⁺): m/z 443.40 [M+H]⁺. Step-3: 7-(3-fluoropyridin-4-yl)-8-(phenylamino)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Example 71) [0635] Prepared using a similar method described for the synthesis of (Ex.19). MS (ESI⁺): m/z 323.20 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.46 (d, J = 2.9 Hz, 1H), 8.12 (d, J = 5.1 Hz, 1H), 7.82 (s, 1H), 7.69 (s, 1H), 7.53 – 7.49 (m, 2H), 7.01 (appt, J = 7.8 Hz, 2H), 6.63 (d, J = 7.6 Hz, 3H), 4.17 (s, 2H), 3.53 (s, 2H). Example 72: 8'-((3-chloro-2-methylphenyl)amino)-7'-(pyrimidin-4-yl)-4'H-spiro[cyclobutane-1,3'- pyrrolo[1,2-a]pyrazin]-1'(2'H)-one

Step-1: 7'-acetyl-8'-bromo-2'-(4-methoxybenzyl)-4'H-spiro[cyclobutane-1,3'-pyrrolo[1,2-a]pyrazin]- 1'(2'H)-one (72-1) [0636] To a stirred solution of 8'-bromo-7'-iodo-2'-(4-methoxybenzyl)-4'H-spiro[cyclobutane-1,3'- pyrrolo[1,2-a]pyrazin]-1'(2'H)-one (700 mg) in 1,4-dioxane were added tributyl(1-ethoxyvinyl)stannane (500 mg) and Pd(PPh₃)₂Cl₂ (39 mg) at RT. The RM was purged with argon gas for 10 min and heated at 100 °C for 4 h, cool to RT and was added 2N HCl in 1,4-dioxane. The RM was heated at 50 °C for 1 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (50 % ethyl acetate in hexane) to afford the title compound (72-1). MS (ESI⁺): m/z 417.27 [M (⁷⁹Br)+H]⁺, 419.27 [M (⁸¹Br)+H]⁺. Step-2: 8'-bromo-2'-(4-methoxybenzyl)-7'-(pyrimidin-4-yl)-4'H-spiro[cyclobutane-1,3'-pyrrolo[1,2- a]pyrazin]-1'(2'H)-one (72-2) [0637] To a stirred solution of 7'-acetyl-8'-bromo-2'-(4-methoxybenzyl)-4'H-spiro[cyclobutane-1,3'- pyrrolo[1,2-a]pyrazin]-1'(2'H)-one (150 mg) in toluene were added ammonium acetate (55 mg), ZnCl₂ (5 mg) and triethyl orthoformate (114 mg) at RT. The RM was heated at 120°C for 24 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (70 % ethyl acetate in hexane) to afford the title compound (72- 2).1H NMR (400 MHz, DMSO-d6): δ 9.13 (s, 1H), 8.80 (d, J = 5.5 Hz, 1H), 8.08 (d, J = 5.4 Hz, 1H), 7.95 (s, 1H), 7.26 (d, J = 8.3 Hz, 2H), 6.90 (d, J = 8.3 Hz, 2H), 4.84 (s, 2H), 4.44 (s, 2H), 3.73 (s, 3H), 2.40 – 2.38 (m, 2H), 1.81 (s, 4H). Step-3: 8'-((3-chloro-2-methylphenyl)amino)-2'-(4-methoxybenzyl)-7'-(pyrimidin-4-yl)-4'H- spiro[cyclobutane-1,3'-pyrrolo[1,2-a]pyrazin]-1'(2'H)-one (72-3) [0638] To a stirred solution of 8'-bromo-2'-(4-methoxybenzyl)-7'-(pyrimidin-4-yl)-4'H- spiro[cyclobutane-1,3'-pyrrolo[1,2-a]pyrazin]-1'(2'H)-one (80 mg) in DMF were added 3-chloro-2- methyl-aniline (75 mg) and CS₂CO₃ (143 mg) at RT. The RM was purged with argon gas for 10 min, followed by the addition of XantPhos (20 mg) and Pd₂(dba)₃ (16 mg). The RM was heated at 120 °C for 16 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (70 % ethyl acetate in hexane) to afford the title compound (72-3). MS (ESI⁺): m/z 514.43 [M+H]⁺. Step-4: 8'-((3-chloro-2-methylphenyl)amino)-7'-(pyrimidin-4-yl)-4'H-spiro[cyclobutane-1,3'-pyrrolo[1,2- a]pyrazin]-1'(2'H)-one (Example 72) [0639] Prepared using a similar method described for the synthesis of (Ex.19). MS (ESI⁺): m/z 394.36 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 9.01 (s, 1H), 8.53 (d, J = 5.5 Hz, 1H), 8.27 (s, 1H), 7.98 (s, 1H), 7.90 (s, 1H), 7.34 (d, J = 5.5 Hz, 1H), 6.87 – 6.81 (m, 2H), 6.39 (d, J = 4.0 Hz, 1H), 4.26 (s, 2H), 2.39 (s, 3H), 2.22 – 2.14 (m, 2H), 2.08 – 2.07 (m, 2H), 1.82 – 1.78 (m, 2H).

Example 73: 6-morpholino-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)- one

Step-1: 8-bromo-6-iodo-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (73-1) [0640] To a stirred solution of 8-bromo-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)- one (2 g) in DMF was added NIS (1.5 g) at RT. The RM was heated at 110 °C for 16 h, cooled to RT and concentrated under reduced pressure. The RM was quenched with saturated Na₂S₂O₃ solution and extracted with DCM. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (1.5% methanol in DCM) to afford the title compound (73-1). MS (ESI⁺): m/z 418.10 [M (⁷⁹Br)+H]⁺, 420.00 [M (⁸¹Br)+H]⁺. Step-2: 8-bromo-6-iodo-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)- one (73-2) [0641] Prepared using a similar method described for the synthesis of (4-1). MS (ESI⁺): m/z 538.27 [M (⁷⁹Br)+H]⁺, 540.30 [M (⁸¹Br)+H]⁺. Step-3: tert-butyl (8-bromo-2-(4-methoxybenzyl)-1-oxo-7-(pyridin-4-yl)-1,2,3,4-tetrahydropyrrolo[1,2- a]pyrazin-6-yl)carbamate (73-3) [0642] Prepared using a similar method described for the synthesis of (Int-4). MS (ESI⁺): m/z 527.09 [M (⁷⁹Br)+H]⁺, 529.09 [M (⁸¹Br)+H]⁺. Step-4: 6-amino-8-bromo-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1 )- one (73-4)

[0643] To an ice cold solution of 8-bromo-6-iodo-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4- dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (1.6 g) in DCM was added TFA (3.5 g), stirred at RT for 4 h, diluted with saturated aq. NaHCO₃ solution and extracted with DCM. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (3% methanol in DCM) to afford the title compound (73-4). MS (ESI⁺): m/z 427.11 [M (⁷⁹Br)+H]⁺, 429.11 [M (⁸¹Br)+H]⁺. Step-5: 8-bromo-2-(4-methoxybenzyl)-6-morpholino-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin- 1(2H)-one (73-5) [0644] NaH (60% in mineral oil) (50 mg) was added in portions to an ice-cold solution of 6-amino- 8-bromo-2-(4-methoxybenzyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (73-4) (380 mg) in DMF and stirred for 20 min, followed by addition of 1-bromo-2-(2-bromoethoxy)ethane (250 mg) at 0°C. The RM was stirred at 80°C for 4 h, diluted with ice-cold water and extracted with DCM. The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (1.5% methanol in MDC) to afford title compound (73-5). MS (ESI⁺): m/z 497.00 [M (⁷⁹Br)+H]⁺, 499.00 [M (⁸¹Br)+H]⁺. Step-6: 2-(4-methoxybenzyl)-6-morpholino-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (73-6) [0645] Prepared using a similar method described for the synthesis of (Int-28). MS (ESI⁺): m/z 510.41 [M+H]⁺. Step-7: 6-morpholino-8-(phenylamino)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Example 73) [0646] Prepared using a similar method described for the synthesis of (Ex.19). MS (ESI⁺): m/z 390.14 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.40 (d, J = 5.0 Hz, 2H), 7.63 (s, 1H), 7.45 (s, 1H), 7.31 (d, J = 5.4 Hz, 2H), 6.93 (appt, J = 7.7 Hz, 2H), 6.56 – 6.54 (m, 3H), 4.05 (s, 2H), 3.64 (s, 4H), 3.51 (s, 2H), 2.96 (s, 4H). Example 74: 2-(1-oxo-8-(phenylamino)-7-(pyridin-4-yl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-6- yl)acetonitrile

Step-1: 2-(7-bromo-8-iodo-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-6-yl)acetonitrile (74-1) [0647] To a stirred solution of 7-bromo-6-(chloromethyl)-8-iodo-3,4-dihydropyrrolo[1,2-a]pyrazin- 1(2H)-one (400 mg) in ACN (10 mL) were added TMSCN (122 mg) and K₂CO₃ (212 mg) at RT. The RM was heated at 70 °C for 1 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (1.5 % methanol in DCM) to afford the title compound (74-1).¹H NMR (400 MHz, DMSO-d6): δ 8.00 (s, 1H), 4.23 (s, 2H), 4.17 (t, J = 5.6 Hz, 2H), 3.53 (s, 2H). Step-2: 2-(7-bromo-1-oxo-8-(phenylamino)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-6-yl)acetonitrile (74-2) [0648] To a stirred solution 2-(7-bromo-8-iodo-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-6- yl)acetonitrile (80 mg) in DMF were added aniline (39 mg), EPhosPdG₄ (24 mg), Ephos (11 mg) and K₃PO₄ (111 mg), purged with argon for 10 min and heated at 50 °C for 3 h, cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (2.5 % methanol in DCM) to afford the title compound (74-2). MS (ESI⁺): m/z 345.25 [M (⁷⁹Br)+H]⁺, 347.25 [M (⁸¹Br)+H]⁺. Step-3: 2-(1-oxo-8-(phenylamino)-7-(pyridin-4-yl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-6- yl)acetonitrile (Example 74) [0649] To a stirred solution 2-(7-bromo-1-oxo-8-(phenylamino)-1,2,3,4-tetrahydropyrrolo[1,2- a]pyrazin-6-yl)acetonitrile (30 mg) in 1,4-dioxane:water (4:1) were added 4-pyridylboronic acid (42 mg), XPhos PdG₂ (13 mg) and K₃PO₄ (46 mg) at RT. The RM was purged with argon gas for 10 min and heated at 60 °C for 3 h, diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (2 % methanol in DCM) to afford the title compound (Ex.74). MS (ESI⁺): m/z 344.12 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d6): δ 8.42 (d, J = 5.2 Hz, 2H), 7.86 (s, 1H), 7.58 (s, 1H), 7.27 (d, J = 5.2 Hz, 2H), 6.91 (appt, J = 7.7 Hz, 2H), 6.54 (d, J = 8.0 Hz, 3H), 4.20 (s, 2H), 4.15 (d, J = 6.3 Hz, 2H), 3.56 (s, 2H). Example 75: 8-((2,3-difluorophenyl)amino)-6-(methoxymethyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one

Step-1: ethyl 4-bromo-5-formyl-1H-pyrrole-2-carboxylate (75-2) [0650] To a solution of DMF (30 g) in anhydrous DCM was added POCl₃ (63 g) dropwise at RT and stirred for 10 min, treated with ethyl 4-bromo-1H-pyrrole-2-carboxylate (75-1) (30 g) in anhydrous DCM, stirred for 20 h, diluted with water and extracted with DCM. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and concentrated under reduced pressure to afford the title compound (75-2) (31 g).¹H NMR (400 MHz, CDCl₃): δ 9.82 (s, 1H), 9.75 (s, 1H), 6.97 (d, J = 2.7 Hz, 1H), 4.43 – 4.33 (m, 2H), 1.40 (t, J = 7.1 Hz, 3H). Step-2: ethyl 4-bromo-5-formyl-3-iodo-1H-pyrrole-2-carboxylate (75-3) [0651] Prepared using a similar method described for the synthesis of (51-1).¹H NMR (300 MHz, DMSO- d6): δ 13.69 (s, 1H), 9.66 (s, 1H), 4.37 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H). Step-3: ethyl 4-bromo-5-(hydroxymethyl)-3-iodo-1H-pyrrole-2-carboxylate (75-4) [0652] To a stirred solution of ethyl 4-bromo-5-formyl-3-iodo-1H-pyrrole-2-carboxylate (75-3) (3.7 g) in THF was added NaBH₄ (0.2 g) portion wise at 0 °C. The RM was stirred at RT for 3 h, quenched with 2N HCl solution and concentrated under reduce pressure. The obtained solid was filtered and collected the filter cake to afford the title compound (75-4).¹H NMR (300 MHz, DMSO- d6): δ 12.47 (s, 1H), 5.12 (t, J = 5.5 Hz, 1H), 4.44 (d, J = 5.5 Hz, 2H), 4.27 (q, J = 7.1 Hz, 2H), 1.32 (t, J = 7.1 Hz, 3H). Step-4: ethyl 4-bromo-3-iodo-5-(methoxymethyl)-1H-pyrrole-2-carboxylate (75-5) [0653] Prepared using a similar method described for the synthesis of (Int-30).¹H NMR (400 MHz, DMSO- d6): δ 12.73 (s, 1H), 4.39 (s, 2H), 4.28 (q, J = 7.1 Hz, 2H), 3.22 (s, 3H), 1.32 (t, J = 7.1 Hz, 3H). Step-5: ethyl 4-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-3-iodo-5-(methoxymethyl)-1H-pyrrole-2- carboxylate (75-6) [0654] Prepared using a similar method described for the synthesis of (1-3).¹H NMR (300 MHz, DMSO- d6): δ 6.99 (t, J = 6.0 Hz, 1H), 4.52 (s, 2H), 4.37 (t, J = 5.9 Hz, 2H), 4.29 (q, J = 7.1 Hz, 2H), 3.26 (s, 3H), 3.20 (d, J = 6.0 Hz, 2H), 1.38 – 1.21 (m, 12H). Step-6: ethyl 4-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-3-((2,3-difluorophenyl)amino)-5- (methoxymethyl)-1H-pyrrole-2-carboxylate (75-7) [0655] To a stirred solution of ethyl 4-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-3-iodo-5- (methoxymethyl)-1H-pyrrole-2-carboxylate (75-6) (400 mg) and 2,3-difluoroaniline (194 mg) in dioxane were added XantPhos (43 mg), Cs₂CO₃ (490 mg) at RT. The RM was purged under a stream of N₂ for 15 min and treated with XantPhos PdG₃ (71 mg). The RM was stirred at 100 °C for 16 h, dilute with ice- water and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (2.5% methanol in DCM) to afford the title compound (75-7) (288 mg).¹H NMR (400 MHz, DMSO- d6): δ 7.37 (s, 1H), 7.14 – 7.00 (m, 1H), 6.85 (q, J = 7.6 Hz, 1H), 6.64 (q, J = 8.5 Hz, 1H), 6.36 (dd, J = 14.4, 6.4 Hz, 1H), 4.50 (s, 2H), 4.43 – 4.19 (m, 2H), 4.08 (q, J = 7.1 Hz, 2H), 3.30 (s, 3H), 3.28 – 3.17 (m, 2H), 1.36 (s, 9H), 1.02 (t, J = 7.1 Hz, 3H). Step-7: ethyl 1-(2-((tert-butoxycarbonyl)amino)ethyl)-3-((2,3-difluorophenyl)amino)-5-(methoxymethyl)- 4-(pyridin-4-yl)-1H-pyrrole-2-carboxylate (75-8) [0656] To a stirred solution of ethyl-4-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-3-((2,3- difluorophenyl) amino)-5-(methoxymethyl)-1H-pyrrole-2-carboxylate (75-7) (150 mg) and 4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (115 mg) in dioxane: water (8:2 ratio) were added K₃PO₄ (179 mg) and cataCXiumA (15 mg). The RM was purged with N₂ for 10 min before the addition of cataCXiumA Pd G₃ (10 mg). The RM was heated at 100 °C for 16 h, diluted with ice-water and extracted with ethyl acetate. The combined organic layer was washed with brine (30 mL), dried over anhydrous Na₂SO_4, and concentrated under reduced pressure to afford crude title compound (75-8), which was used as such in the next step without further purification and characterization. Step-8: ethyl 1-(2-aminoethyl)-3-((2,3-difluorophenyl)amino)-5-(methoxymethyl)-4-(pyridin-4-yl)-1H- pyrrole-2-carboxylate (75-9) [0657] Prepared using a similar method described for the synthesis of (Int-1). MS (ESI⁺): m/z 431.10 [M+H]⁺ Step-9: 8-((2,3-difluorophenyl)amino)-6-(methoxymethyl)-7-(pyridin-4-yl)-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (Example 75) [0658] Prepared using a similar method described for the synthesis of (Int-1). MS (ESI⁺): m/z 385.10 [M+H]⁺. ¹H NMR (400 MHz, DMSO- d6): δ 8.46 – 8.45 (m, 2H), 7.90 (d, J = 2.8 Hz, 1H), 7.63 (s, 1H), 7.31 – 7.29 (m, 2H), 6.65 – 6.52 (m, 2H), 6.12 (appt, J = 8.0 Hz, 1H), 4.40 (s, 2H), 4.15 (t, J = 5.2 Hz, 2H), 3.54 (s, 2H), 3.32 (s, 3H).

Example 76: (R)-8-((2,3-difluorophenyl)amino)-6-(methoxymethyl)-4,4-dimethyl-7-(thieno[3,2- d]pyrimidin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one and Example 77: (S)-8-((2,3-difluorophenyl)amino)-6-(methoxymethyl)-4,4-dimethyl-7-(thieno[3,2- d]pyrimidin-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

Step-1: 4-bromo-3-iodo-5-(methoxymethyl)-1H-pyrrole-2-carboxylic acid (76-1) [0659] To a stirred solution of t-BuOK (24.2 g) in THF and water at 0 °C was added ethyl 4-bromo- 3-iodo-5-(methoxymethyl)-1H-pyrrole-2-carboxylate (75-5) (9.3 g) in portions over 30 min at 0 °C. The RM was stirred at 0 °C for 1 h, quenched with saturated NH₄Cl solution, extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO₄ concentrated under reduced pressure. The residue was triturated with DCM to afford the title compound (76-1). MS (ESI⁺): m/z 358.00 [M (⁷⁹Br) –H]⁺, 360.00 [M (⁸¹Br) –H]⁺. Step-2: 4-bromo-N-(2-hydroxy-2-methylpropyl)-3-iodo-N-(4-methoxybenzyl)-5-(methoxymethyl)-1H- pyrrole-2-carboxamide (76-2) [0660] To a stirred solution of 4-bromo-3-iodo-5-(methoxymethyl)-1H-pyrrole-2-carboxylic acid (76-1) (7.9 g), HATU (12.5 g) and DIEA (8.5 g) in DMAc at RT was added 1-((4- methoxybenzyl)amino)-2-methylpropan-2-ol (5.5 g) in portions over 30 min at RT. The RM was stirred for 2 h, diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous Na₂SO_4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (50 % ethyl acetate in hexane) to afford the title compound (76-2). MS (ESI⁺): m/z 351.20 [M (⁷⁹Br)+H]⁺, 353.20 [M (⁸¹Br)+H]⁺. Step-3: 7-bromo-8-iodo-2-(4-methoxybenzyl)-6-(methoxymethyl)-4,4-dimethyl-3,4-dihydropyrrolo[1,2- a]pyrazin-1(2H)-one (76-3) [0661] Prepared using a similar method described for the synthesis of (1-3). MS (ESI⁺): m/z 533.00 [M+H]⁺ Step-4: 7-bromo-8-(2,3-difluoroanilino)-6-(methoxymethyl)-2-[(4-methoxyphenyl)methyl]-4,4-dimethyl- 3H-pyrrolo[1,2-a]pyrazin-1-one (76-4) [0662] To a stirred solution of 7-bromo-8-iodo-2-(4-methoxybenzyl)-6-(methoxymethyl)-4,4- dimethyl-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (76-3) (4 g) and 2,3-difluoroaniline (1.9 g) in toluene were added K₃PO₄ (1.8 g) and XantPhos (0.4 g). The RM was purged under a stream of N₂ for 15 min and treated with XantPhos PdG₃ (0.7 g). The RM was stirred at 100 °C for 18 h, dilute with water and extracted with ethyl acetate. The combined organic layer was washed with brine solution (30 mL), dried over anhydrous Na₂SO_4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (50 % ethyl acetate in hexane) to afford the title compound (76-4). MS (ESI⁺): m/z 534.11 [M (⁷⁹Br)+H]⁺, 536.11 [M (⁸¹Br)+H]⁺. Step-5: 8-((2,3-difluorophenyl)amino)-2-(4-methoxybenzyl)-6-(methoxymethyl)-4,4-dimethyl-7-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-on (76-5) [0663] To a stirred solution of 7-bromo-8-(2,3-difluoroanilino)-6-(methoxymethyl)-2-[(4- methoxyphenyl)methyl]-4,4-dimethyl-3H-pyrrolo[1,2-a]pyrazin-1-one (76-4) (1 g), 1,4-dioxane were added 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.7 g), TEA (0.6 g) at RT. The RM was purged under a stream of N₂ for 15 min and treated with tetrakis Pd(0) (0.2 g). The RM was stirred at 100 °C for 18 h, cooled to RT, diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine solution (15 mL), dried over anhydrous Na₂SO₄ and evaporated under reduced pressure. The residue was purified by reversed-phase flash chromatography (conditions: column, C18 silica gel; mobile phase, ACN in water (0.05% NH₄OH), 20% to 100% gradient in 10 min; detector, UV 254 nm) to afford the title compound (76-5). MS (ESI⁺): m/z 582.00 [M+H]⁺ Step-6: 8-(2,3-difluoroanilino)-6-(methoxymethyl)-2-[(4-methoxyphenyl)methyl]-4,4-dimethyl-7- thieno[3,2-d]pyrimidin-4-yl-3H-pyrrolo[1,2-a]pyrazin-1-one (76-6) [0664] Prepared using a similar method described for the synthesis of (53-2). MS (ESI⁺): m/z 590.40 [M+H]⁺. Step-7: 8-((2,3-difluorophenyl)amino)-7-(4,4a-dihydrothieno[3,2-d]pyrimidin-4-yl)-6-(methoxymethyl)- 4,4-dimethyl-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (76-7) [0665] To a stirred solution 8-(2,3-difluoroanilino)-6-(methoxymethyl)-2-[(4- methoxyphenyl)methyl]-4,4-dimethyl-7-thieno[3,2-d]pyrimidin-4-yl-3H-pyrrolo[1,2-a]pyrazin-1-one (76- 6) (0.2 g) in DCM was added MSA at RT. The RM was stirred at RT for 45 h, quenched with NH₄OH (28% in water) at 0 °C and extracted with DCM. The combined organic layers were washed with brine, dried over anhydrous Na₂SO_4, and concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography (conditions: column, C18 silica gel; mobile phase, ACN in water (0.05% NH₄OH), 20% to 100% gradient in 10 min; detector, UV 254 nm) to afford (76-7). Step-8: Chiral separation of Example 76 and Example 77: [0666] These two atropisomers were separated by SFC (Column: XA-CHIRAL ART Cellulose-SC, 3*25 cm, 5 μm; Mobile Phase A: CO2, Mobile Phase B: MeOH(0.1% 2M NH3-MeOH); Flow rate: 80 mL/min; Gradient: isocratic 50% B; Column Temperature(℃): 35; Back Pressure(bar): 100; Wave Length: 220 nm; RT1(min): 4.22; RT2(min): 5.93; Sample Solvent: DCM; Injection Volume: 5 mL). They are separately marked in AUR-0011979 and AUR-0011980. [0667] Example 76: (arbitrarily assigned stereochemistry) MS (ESI⁺): m/z 470.10 [M+H]⁺ ; ¹H NMR (400 MHz, ACN-d₃): δ 8.08 (s, 1H), 7.18 (d, J = 5.2 Hz, 1H), 7.14 (s, 1H), 7.03 (s, 1H), 6.75 (dd, J = 18.0, 7.3 Hz, 2H), 6.51 (s, 1H), 6.07 (s, 1H), 4.31 (s, 2H), 3.35 (d, J = 4.0 Hz, 2H), 3.06 (s, 3H), 1.56 (d, J = 7.5 Hz, 6H). [0668] Example 77: (arbitrarily assigned stereochemistry) MS (ESI⁺): m/z 470.10 [M+H]⁺ ; ¹H NMR (400 MHz, ACN-d₃): δ 8.08 (s, 1H), 7.18 (d, J = 5.2 Hz, 1H), 7.14 (s, 1H), 7.03 (s, 1H), 6.75 (dd, J = 18.0, 7.3 Hz, 2H), 6.51 (s, 1H), 6.07 (s, 1H), 4.31 (s, 2H), 3.35 (d, J = 4.0 Hz, 2H), 3.06 (s, 3H), 1.56 (d, J = 7.5 Hz, 6H). V. BIOLOGICAL ASSAYS Biochemical EGFR Inhibition Assays [0669] The kinase activity of the EGFR variants were determined using a real-time fluorescent peptide sensor of kinase activity as described previously (Zhai et al., Biochemistry 59(14):1428-1441 (2020), which is hereby incorporated by reference in its entirety). IC50s were determined by measuring the fluorescence at varying concentrations of the compounds. Assays were performed in the following reaction conditions: 52 mM HEPES pH 7.5, 1.1 mM DTT, 0.011% Brij-35, 5% glycerol, 0.2 mg/ml BSA, 250 µM MnCl2, 0.52 mM EGTA, 10 mM MgCl2, 1% DMSO, 15 μM AQT0734 (AssayQuant Technologies). For potent compounds, 1 mM ATP was used, otherwise, ATP concentrations were as stated in Table 2. Enzymes and compounds were first pre-incubated for 30 minutes at 37°C to equilibrate before starting the kinase reaction. Assays were performed in duplicate with several biological repeats. Ki data were calculated from IC₅₀ measurements based on the Cheng-Prusoff Equation below and the average Ki values were included in Table 4. Depending on the assay, the enzymes and ATP concentrations identified in Table 2 were included. Cheng-Prusoff Equation: Ki = IC₅₀/(1+[S]/K_m) Ki = the concentration of an inhibitor where 50% of the receptor sites are occupied if no competing substrate is present IC₅₀ = 50% maximal inhibitory concentration [S] = the concentration of ATP used in the assay K_m = the concentration of ATP that leads to 50% maximal enzymatic activity [0670] Table 18. Enzymes for EGFR Inhibition Assays and ATP Concentrations

Cellular Phospho-EGFR HTRF Assay [0671] Target engagement assays to measure pEGFR were used to measure cellular activity of the EGFR inhibitor compounds. The commercially available AlphaLISA SureFire Ultra p-EGFR (Tyr1068) assay kit (PerkinElmber ALSU-PEGFR-A50K) was used according to the manufacturer's instructions. Briefly, 40 uL of Ba/F3 EGFR L858R/C797S, PC-9, or A431 cells were seeded in 384 well plates (Corning 3764) diluted in their culture medium (see table 3 for cell number and culture medium for each cell line). Plates were covered and placed in a 37°C, 5% CO₂ incubator overnight. Cells were treated with 40 nL of compounds in DMSO in a 3-fold, 10-point serial dilution and incubated for 2 hours. Plates were centrifuged at room temperature for 10 minutes at 3,000 rpm and 40 uL of medium was removed using an apricot liquid handler.10 uL of 1x lysis buffer was added to each well and plates were shaken at 600 rpm for 1 hour.5 uL of AlphaLISA acceptor mix was added to each well and plates were shaken at 350 rpm for 1 hour in the dark.5 uL of donor mix was added to each well, plates were mixed on a shaker, and plates were sealed and wrapped in aluminum foil and incubated overnight at room temperature.18.5 uL of the mixture was transferred to a white optiplate 384 well plate (PerkinElmer 6007290) using an apricot liquid handler, and the plates were read on an Envision plate reader using standard AlphaLISA settings. [0672] Table 19. Cell Number and Culture Medium

[0673] In Table 20, the EGFR LR/CS and EGFR Del19 K_i ranges are as follows: A: K_i < 10 nM; B: 10 nM ≤ K_i ≤ 100 nM; C: K_i > 100 nM. A value of “NA” indicates that no K_i value was available for the compound and does not necessarily indicate that the compound is inactive in the referenced assay. [0674] Table 20. Results of Biochemical EGFR Inhibition Assays

[0675] In Table 21, the PC-9 and BaF3 EGFR (LR/CS) IC₅₀ ranges are as follows: A: IC₅₀ < 100 nM; B: 100 nM ≤ IC₅₀ ≤ 1000 nM; C: IC₅₀ > 1000 nM. A value of “NA” indicates that no IC₅₀ value was available for the compound and does not necessarily indicate that the compound is inactive in the referenced assay. [0676] Table 21. Results of Cellular P57hospho-EGFR HTRF Assay

[0677] Although the foregoing embodiments have been described in some detail by way of illustration and Example for purposes of clarity of understanding, one of skill in the art will appreciate that certain changes and modifications may be practiced within the scope of the appended claims. Where a conflict exists between the instant application and a reference provided herein, the instant application shall dominate.

Claims

CLAIMS What is claimed is: 1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein: Ring A is a C₆-C₁₀ aryl or 5- to 10-membered heteroaryl; X is CH or N; R¹ is hydrogen or C₁-C₃ alkyl; R², R³, R⁴ and R⁵ are independently selected at each occurrence from the group consisting of hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, and –(C₁-C₃ alkylene)-O-R¹¹, wherein R² and R³ or R⁴ and R⁵ may optionally be taken together with the atom to which they are attached to form a 3- to 6-membered cycloalkyl or a 4- to 7-membered heterocyclyl, or R² or R³ and R⁴ or R⁵ may optionally be taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring; R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, phenyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –(CH₂)_mO(CH₂)_m-(C₁-C₃ alkoxy), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(aryl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(heteroaryl), –NH-aryl, –C(O)-(4- to 7-membered heterocyclyl), heteroaryl, 4- to 10-membered heterocyclyl, 3- to 6-membered cycloalkyl, –CH₂S(O)₂CH₃, –CH₂S(O)NCH₃ and cyano; R⁷ is selected from hydrogen, halo, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, –C₁-C₄ alkylene-(C₁-C₃ alkoxy), 3- to 6-membered cycloalkyl, –O-(3- to 6-membered cycloalkyl), –O-heteroaryl, –O-(C₁-C₄ alkylene)-(C₁-C₃ alkoxy), –O-(C₁-C₃ alkoxy)-heteroaryl, –O-(C₁-C₄ alkylene)-(4- to 7-membered heterocyclyl), –O-(C₁-C₄ alkylene)-O-(3- to 6-membered cycloalkyl), –NH-CH₂-heteroaryl, –O-CH₂-heteroaryl and ; R⁸ is hydrogen, C₁-C₃ alkyl, or C₁-C₆ haloalkyl; or R⁷ and R⁸ are taken together to form a fused bicyclic heteroaromatic ring; R⁹ is independently selected at each occurrence thereof from the group consisting of halogen, cyano, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, and –O-(C₁-C₃ haloalkyl); R¹⁰ is selected from heterocyclyl, cycloalkyl, and heteroaryl; R¹¹ is C₁-C₃ alkyl or heteroaryl; m is 0, 1, 2 or 3; and n is 0, 1, 2, 3, 4 or 5; wherein: each alkyl is optionally substituted with one or more substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₃-C₆ cycloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy and –OCD₃; each cycloalkyl is optionally substituted with one to three substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy and –OCD₃; each heterocyclyl ring is optionally substituted with one to four substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₃-C₆ cycloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy, –OCD₃, –S(O)₂CH₃, –C(O)-C₁-C₃ alkyl, and 5-membered heteroaryl optionally substituted with one C₁-C₃ alkyl; each aryl is optionally substituted with one to three substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl and C₁-C₃ alkoxy; and each heteroaryl, or bicyclic heteroaryl is optionally substituted with one to three substituents each independently selected from the group consisting of: halo, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, , an optionally substituted –O-(C₃-C₆ cycloalkyl) and an optionally substituted –O-(4- to 6-membered heterocyclyl). 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R², R³, R⁴ and R⁵ are independently selected at each occurrence from the group consisting of hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, and –(C₁-C₃ alkylene)-O-R¹¹, wherein R² and R³ or R⁴ and R⁵ may optionally be taken together with the atom to which they are attached to form a 3- to 6-membered cycloalkyl, or R² or R³ and R⁴ or R⁵ may optionally be taken together with the atoms to which they are attached to form a 3- to 6-membered cycloalkyl or heterocyclic ring. 3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: R² is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; R³ is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; or R² and R³, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a; R⁴ is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; R⁵ is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; or R⁴ and R⁵, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a; or one of R² and R³ and one of R⁴ and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclic ring, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a; R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, phenyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –(CH₂)_mO(CH₂)_m-(C₁-C₃ alkoxy), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(C₆-C₁₀ aryl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl), –NH-(C₆-C₁₀ aryl), –C(O)-(4- to 7-membered heterocyclyl), 5- to 10-membered heteroaryl, 4- to 10-membered heterocyclyl, C₃-C₆ cycloalkyl, –CH₂S(O)₂CH₃, –CH₂S(O)NCH₃, cyano, and C₁-C₃ cyanoalkyl, wherein said 4- to 10-membered heterocyclyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), or –C(O)-(4- to 7-membered heterocyclyl) is optionally substituted with 1-4 R^a, and said 5- to 10-membered heteroaryl or –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) is optionally substituted with 1-3 R^b; R⁷ is selected from hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, –C₁-C₄ alkylene-(C₁-C₃ alkoxy), C₃-C₆ cycloalkyl, –O-(C₃-C₆ cycloalkyl), –O-(5- to 10-membered heteroaryl), –O-(C₁-C₄ alkylene)-(C₁-C₃ alkoxy), –O-(C₁-C₃ alkoxy)-(5- to 10-membered heteroaryl), –O-(C₁-C₄ alkylene)-(4- to 7-membered heterocyclyl), –O-(C₁-C₄ alkylene)-O-(C₃-C₆ cycloalkyl), –NH-CH₂-(5- to 10-membered heteroaryl), –O-CH₂-(5- to 10-membered heteroaryl), and , wherein said –O-(C₁-C₄ alkylene)-(4- to 7-membered heterocyclyl) is optionally substituted with 1-4 R^a, and said –O-(5- to 10-membered heteroaryl), –O-(C₁-C₃ alkoxy)-(5- to 10-membered heteroaryl), or –NH-CH₂-(5- to 10-membered heteroaryl) is optionally substituted with 1-3 R^b; R⁸ is hydrogen, C₁-C₃ alkyl, or C₁-C₆ haloalkyl; or R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1-3 R^c; each R⁹ is independently selected from the group consisting of halogen, cyano, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, and –O-(C₁-C₃ haloalkyl); R¹⁰ is selected from 4- to 7-membered heterocyclyl optionally substituted with 1-3 R^a, C₃-C₆ cycloalkyl, and 5- to 10-membered heteroaryl optionally substituted with 1-3 R^b; each R¹¹ is independently C₁-C₃ alkyl or 5- to 10-membered heteroaryl, wherein said 5- to 10-membered heteroaryl is optionally substituted with 1-3 R^b; each R^a is independently selected from halogen, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₃-C₆ cycloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy, –OCD₃, –S(O)₂CH₃, –C(O)-C₁-C₃ alkyl, and 5-membered heteroaryl optionally substituted with one C₁-C₃ alkyl; each R^b is independently selected from halogen, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, –O-(C₃-C₆ cycloalkyl), and –O-(4- to 6-membered heterocyclyl) optionally substituted with 1-4 R^a; each R^c is independently selected from halogen, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, –O-(C₃-C₆ cycloalkyl), and –O-(4- to 6-membered heterocyclyl) optionally substituted with 1-4 R^a; and each m is independently 0, 1, 2, or 3. 4. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein: Ring A is C₆-C₁₀ aryl or 5- to 10-membered heteroaryl; X is CH or N; R¹ is hydrogen or C₁-C₃ alkyl; R² is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; R³ is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; or R² and R³, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a; R⁴ is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; R⁵ is hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or –(C₁-C₃ alkylene)-O-R¹¹; or R⁴ and R⁵, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a; or one of R² and R³ and one of R⁴ and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclic ring, wherein said 4- to 7-membered heterocyclyl is optionally substituted with 1-4 R^a; R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, phenyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –(CH₂)_mO(CH₂)_m-(C₁-C₃ alkoxy), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(C₆-C₁₀ aryl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl), –NH-(C₆-C₁₀ aryl), –C(O)-(4- to 7-membered heterocyclyl), 5- to 10-membered heteroaryl, 4- to 10-membered heterocyclyl, C₃-C₆ cycloalkyl, –CH₂S(O)₂CH₃, –CH₂S(O)NCH₃, cyano, and C₁-C₃ cyanoalkyl, wherein said 4- to 10-membered heterocyclyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), or –C(O)-(4- to 7-membered heterocyclyl) is optionally substituted with 1-4 R^a, and said 5- to 10-membered heteroaryl or –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) is optionally substituted with 1-3 R^b; R⁷ is selected from hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, –C₁-C₄ alkylene-(C₁-C₃ alkoxy), C₃-C₆ cycloalkyl, –O-(C₃-C₆ cycloalkyl), –O-(5- to 10-membered heteroaryl), –O-(C₁-C₄ alkylene)-(C₁-C₃ alkoxy), –O-(C₁-C₃ alkoxy)-(5- to 10-membered heteroaryl), –O-(C₁-C₄ alkylene)-(4- to 7-membered heterocyclyl), –O-(C₁-C₄ alkylene)-O-(C₃-C₆ cycloalkyl), –NH-CH₂-(5- to 10-membered heteroaryl), –O-CH₂-(5- to 10-membered heteroaryl), and , wherein said –O-(C₁-C₄ alkylene)-(4- to 7-membered heterocyclyl) is optionally substituted with 1-4 R^a, and said –O-(5- to 10-membered heteroaryl), –O-(C₁-C₃ alkoxy)-(5- to 10-membered heteroaryl), or –NH-CH₂-(5- to 10-membered heteroaryl) is optionally substituted with 1-3 R^b; R⁸ is hydrogen, C₁-C₃ alkyl, or C₁-C₆ haloalkyl; or R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with 1-3 R^c; each R⁹ is independently selected from the group consisting of halogen, cyano, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, and –O-(C₁-C₃ haloalkyl); R¹⁰ is selected from 4- to 7-membered heterocyclyl optionally substituted with 1-3 R^a, C₃-C₆ cycloalkyl, and 5- to 10-membered heteroaryl optionally substituted with 1-3 R^b; each R¹¹ is independently C₁-C₃ alkyl or 5- to 10-membered heteroaryl, wherein said 5- to 10-membered heteroaryl is optionally substituted with 1-3 R^b; each R^a is independently selected from halogen, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₃-C₆ cycloalkyl, C₁-C₃ alkoxy, C₁-C₃ alkoxyhydroxy, –OCD₃, –S(O)₂CH₃, –C(O)-C₁-C₃ alkyl, and 5-membered heteroaryl optionally substituted with one C₁-C₃ alkyl; each R^b is independently selected from halogen, oxo, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, –O-(C₃-C₆ cycloalkyl), and –O-(4- to 6-membered heterocyclyl) optionally substituted with 1-4 R^a; each R^c is independently selected from halogen, cyano, hydroxy, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, –O-(C₃-C₆ cycloalkyl), and –O-(4- to 6-membered heterocyclyl) optionally substituted with 1-4 R^a; each m is independently 0, 1, 2, or 3; and n is 0, 1,

2,

3,

4, or 5.

5. The compound of any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (I-A):

6. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein X is CH.

7. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein X is N.

8. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein Ring A is C₆-C₁₀ aryl, optionally wherein Ring A is phenyl.

9. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein Ring A is 5- to 10-membered heteroaryl, optionally wherein Ring A is selected from phenyl, benzo[d]isothiazol-3-yl, benzo[d]thiazol-4-yl, and quinolin-8-yl.

10. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2.

11. The compound of any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein each R⁹ is independently selected from the group consisting of halogen, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, and –O-(C₁-C₃ haloalkyl), optionally wherein each R⁹ is independently selected from the group consisting of Cl, F, –CH₃, –CH₂CH₃, –OCH₃, –CF₃, and –OCHF₂.

12. The compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from: ,

12. The compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen or C₁-C₃ alkyl, optionally wherein R¹ is hydrogen or –CH₃.

13. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein R² is hydrogen or C₁-C₆ alkyl, optionally wherein R² is hydrogen or –CH₃.

14. The compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein R³ is hydrogen or C₁-C₆ alkyl, optionally wherein R³ is hydrogen or –CH₃.

15. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein R² and R³, together with the carbon atom to which they are attached, form a C₃-C₆ cycloalkyl or a 4- to 7-membered heterocyclyl, optionally wherein the C₃-C₆ cycloalkyl is cyclobutyl or the 4- to 7-membered heterocyclyl is oxetanyl.

16. The compound of any one of claims 1 to 15, or a pharmaceutically acceptable salt thereof, wherein R⁴ is hydrogen or C₁-C₆ alkyl, optionally wherein R⁴ is hydrogen or –CH₃.

17. The compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein R⁵ is hydrogen or C₁-C₆ alkyl, optionally wherein R⁵ is hydrogen or –CH₃.

18. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein one of R² and R³ and one of R⁴ and R⁵, together with the carbon atoms to which they are attached, form a C₃-C₆ cycloalkyl, optionally wherein the C₃-C₆ cycloalkyl is cyclopentyl.

19. The compound of claim 18, or a pharmaceutically acceptable salt thereof, wherein two of R², R³, R⁴, and R⁵ are hydrogen.

20. The compound of any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, wherein R⁶ is selected from hydrogen, halogen, C₁-C₃ alkyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), –(CH₂)_mO-(C₁-C₆ alkyl), –CH₂O-(C₁-C₆ haloalkyl), –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl), –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl), 5- to 10-membered heteroaryl, 4- to 10-membered heterocyclyl, cyano, and C₁-C₃ cyanoalkyl, wherein said 4- to 10-membered heterocyclyl, –C₁-C₃ alkylene-(4- to 7-membered heterocyclyl), or –CH₂O-(CH₂)_m-(4- to 6-membered heterocyclyl) is optionally substituted with 1-4 R^a, and said 5- to 10-membered heteroaryl or –CH₂O-(CH₂)_m-(5- to 10-membered heteroaryl) is optionally substituted with 1-3 R^b.

21. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein m is 0, 1, or 2.

22. The compound of claim 20 or 21, or a pharmaceutically acceptable salt thereof, wherein each R^a is independently selected from halogen, oxo, C₁-C₃ alkyl, and C₁-C₃ alkoxy.

23. The compound of any one of claims 20 to 22, or a pharmaceutically acceptable salt thereof, wherein each R^b is independently selected from C₁-C₃ alkyl.

24. The compound of any one of claims 1 to 23, or a pharmaceutically acceptable salt thereof, wherein R⁶ is selected from hydrogen, Cl, –CH₃, –CH₂CN,

,

_,

25. The compound of any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein R⁷ is selected from hydrogen, halogen, and .

26. The compound of claim 25, or a pharmaceutically acceptable salt thereof, wherein R¹⁰ is 5- to 10-membered heteroaryl optionally substituted with 1-3 R^b.

27. The compound of claim 26, or a pharmaceutically acceptable salt thereof, wherein each R^b is independently selected from C₁-C₃ alkyl.

28. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, _{wherein R} ⁷ _{is selected from hydrogen,}

29. The compound of any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, wherein R⁸ is hydrogen.

30. The compound of any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸, together with the carbon atoms to which they are attached, form a fused heteroaromatic ring optionally substituted with one R^c.

31. The compound of claim 30, wherein R⁷ and R⁸, or a pharmaceutically acceptable salt thereof, together with the carbon atoms to which they are attached, form a fused furanyl, thiophenyl, thiazolyl, or pyridinyl, wherein the fused furanyl, thiophenyl, thiazolyl, or pyridinyl is optionally substituted with one R^c.

32. The compound of claim 31, or a pharmaceutically acceptable salt thereof, wherein R^c is C₁-C₃ alkoxy, optionally wherein R^c is –OCH₃.

33. The compound of any one of claims 1 to 24 or 30-32, or a pharmaceutically acceptable salt thereof, wherein R⁷ and R⁸ are taken together with the heteroaromatic ring on which they reside to form

.

34. A compound selected from Table A or Examples 1 to 77, or a pharmaceutically acceptable salt thereof.

35. A compound selected from Table B, or a pharmaceutically acceptable salt thereof.

36. The compound of any one of claims 1 to 35, or a pharmaceutically acceptable salt thereof, wherein the compound is an EGFR inhibitor selective to a mutant EGFR protein or gene.

37. The compound of any one of claims 1 to 36, wherein the compound is in a non-salt form.

38. A pharmaceutical composition comprising a compound of any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, or the compound of claim 37 and one or more pharmaceutically acceptable carriers or vehicles.

39. A method of inhibiting EGFR in a subject comprising administering to the subject the compound of any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, the compound of claim 37, or the pharmaceutical composition of claim 38.

40. A method of treating cancer in a subject, comprising administering to the subject an effective amount of a compound of any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, the compound of claim 37, or the pharmaceutical composition of claim 38.

41. The method of claim 40, wherein the cancer is an EGFR-associated cancer.

42. The method of any one of claims 39 to 41, wherein said subject is treated with one or more additional therapeutic agents administered concurrently with, prior to, or subsequent to treatment with the compound, pharmaceutically acceptable salt, or pharmaceutical composition.

43. Use of the compound of any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, the compound of claim 37, or the pharmaceutical composition of claim 38, as a medicament.

44. Use of the compound of any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, the compound of claim 37, or the pharmaceutical composition of claim 38 in the manufacture of a medicament for treating cancer.