Nothing Special   »   [go: up one dir, main page]

HRP20161115T1 - Aril- ili heteroaril-supstituirani spojevi benzena - Google Patents

Aril- ili heteroaril-supstituirani spojevi benzena Download PDF

Info

Publication number
HRP20161115T1
HRP20161115T1 HRP20161115TT HRP20161115T HRP20161115T1 HR P20161115 T1 HRP20161115 T1 HR P20161115T1 HR P20161115T T HRP20161115T T HR P20161115TT HR P20161115 T HRP20161115 T HR P20161115T HR P20161115 T1 HRP20161115 T1 HR P20161115T1
Authority
HR
Croatia
Prior art keywords
image
alkyl
alkylamino
halo
membered heterocycloalkyl
Prior art date
Application number
HRP20161115TT
Other languages
English (en)
Inventor
Kevin Wayne Kuntz
Richard Chesworth
Kenneth William Duncan
Heike KEILHACK
Natalie WARHOLIC
Christine KLAUS
Masashi Seki
Syuji SHIROTORI
Satoshi Kawano
Timothy James Nelson Wigle
Sarah Kathleen Knutson
Original Assignee
Epizyme, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=46045109&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HRP20161115(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Epizyme, Inc. filed Critical Epizyme, Inc.
Publication of HRP20161115T1 publication Critical patent/HRP20161115T1/hr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyridine Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Claims (16)

1. Spoj s formulom (I) ili njegova farmaceutski prihvatljiva sol: [image] naznačen time da X1 je N ili CR11; X2 je N ili CR13; Z je NR7R8, OR7, S(O)nR7, ili CR7R8R14, gdje n je 0, 1, ili 2; svaki od R1, R5, R9, i R10, neovisno, je H ili C1-C6 alkil proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, hidroksil, COOH, C(O)O-C1-C6 alkil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, i 5- ili 6-člani heteroaril; svaki od R2, R3, i R4, neovisno, je -Q1-T1, gdje Q1 je veza ili C1-C3 alkil poveznica proizvoljno supstituirana s halo, cijano, hidroksil ili C1-C6 alkoksi, i T1 je H, halo, hidroksil, COOH, cijano, ili RS1, gdje RS1 je C1-C3 alkil, C2-C6 alkenil, C2-C6 alkinil, C1-C6 alkoksil, C(O)O-C1-C6 alkil, C3-C8 cikloalkil, C6- C10 aril, amino, mono-C1-C6 alkilamino, di-C1-C6alkilamino, 4 do 12-člani heterocikloalkil, ili 5- ili 6-člani heteroaril, i RS1 je proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, hidroksil, okso, COOH, C(O)O-C1-C6 alkil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, i 5- ili 6-člani heteroaril; R6 je C6-C10 aril ili 5- ili 6-člani heteroaril, svaki od kojih je proizvoljno supstituiran s jednim ili više -Q2-T2, pri čemu Q2 je veza ili C1-C3 alkil poveznica proizvoljno supstituirana s halo, cijano, hidroksil ili C1-C6 alkoksi, i T2 je H, halo, cijano, -ORa, -NRaRb, -(NRaRbRC)+A-,-C(O)Ra, -C(O)ORa, - C(O)NRaRb, -NRbC(O)Ra, -NRbC(O)ORa, -S(O)2Ra, -S(O)2NRaRb, ili Rs2, gdje svaki od Ra, Rb, i RC, neovisno je H ili RS3, A- je farmaceutski prihvatljiv anion, svaki od RS2 i RS3, neovisno, je C1-C6 alkil, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, ili 5- ili 6-člani heteroaril, ili Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore 4 do 12-člani heterocikloalkilni prsten koji ima 0 ili 1 dodatni heteroatom, i svaki od RS2, RS3, te 4 do 12-člani heterocikloalkilni prsten koji tvore Ra i Rb, je proizvoljno supstituiran s jednim ili više -Q3-T3, pri čemu Q3 je veza ili C1-C3 alkil poveznica svaki proizvoljno supstituiran s halo, cijano, hidroksil ili C1-C6 alkoksi, i T3 se bira iz skupine koju čine halo, cijano, C1-C6 alkil, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, 5- ili 6-člani heteroaril, ORd, COORd, -S(O)2Rd, -NRdRe, i -C(O)NRdRe, svaki od R i Re neovisno je H ili C1-C6 alkil, ili -Q3-T3 je okso; ili bilo koja dva susjedna -Q2-T2, zajedno s atomima na koje su oni vezani tvore 5- ili 6-člani prsten koji proizvoljno sadrži 1-4 heteroatoma koji se biraju od N, O i S i proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, hidroksil, COOH, C(O)O-C1-C6 alkil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, i 5- ili 6-člani heteroaril; R7 je -Q4-T4, gdje Q4 je veza, C1-C4 alkil poveznica, ili C2-C4 alkenil poveznica, svaki poveznica proizvoljno supstituirana s halo, cijano, hidroksil ili C1-C6 alkoksi, i T4 je H, halo, cijano, NRfRg, -ORf, -C(O)Rf, -C(O)ORf, - C(O)NRfRg, -C(O)NRfORg, -NRfC(O)Rg, -S(O)2Rf, ili Rs4, gdje svaki od Rf i Rg, neovisno je H ili RS5, svaki od RS4 i RS5, neovisno je C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, ili 5- ili 6-člani heteroaril, i svaki od RS4 i RS5 je proizvoljno supstituiran s jednim ili više -Q5-T5, pri čemu Q5 je veza, C(O), C(O)NRk, NRkC(O), S(O)2, ili C1-C3 alkil poveznica, Rk je H ili C1-C6 alkil, i T5 je H, halo, C1-C6 alkil, hidroksil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, 5- ili 6-člani heteroaril, ili S(O)qRq gdje q je 0, 1, ili 2 i Rq je C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C6-C10 aril, 4 do 12- člani heterocikloalkil, ili 5- ili 6-člani heteroaril, i T5 je proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, C1-C6 alkil, hidroksil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, te 5- ili 6-člani heteroaril osim kada T5 je H, halo, hidroksil, ili cijano; ili -Q5-T5 je okso; svaki od R8, R11, R12, i R13, neovisno, je H, halo, hidroksil, COOH, cijano, RS6, ORS6, ili COORS6, gdje RS6 je C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, 4 do 12-člani heterocikloalkil, amino, mono-C1-C6 alkilamino, ili di-C1-C6 alkilamino, i RS6 je proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, hidroksil, COOH, C(O)O-C1-C6 alkil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, i di-C1-C6 alkilamino; ili R7 i R8, zajedno s atomom N na koji su oni spojeni, tvore 4 do 11-člani heterocikloalkilni prsten koji ima 0 to 2 dodatnih heteroatoma, ili R7 i R8, zajedno s atomom C na koji su oni vezani, tvore C3- C8 cikloalkil ili 4 do 11-člani heterocikloalkilni prsten koji ima 1 do 3 heteroatoma, te svaki od 4 do 11-članih heterocikloalkilnih prstena ili C3-C8 cikloalkil koji tvore R7 i R8 je proizvoljno supstituiran s jednim ili više -Q6-T6, pri čemu Q6 je veza, C(O), C(O)NRm, NRmC(O), S(O)2, ili C1-C3 alkil poveznica, Rm je H ili C1-C6 alkil, i T6 je H, halo, C1-C6 alkil, hidroksil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, 5- ili 6-člani heteroaril, ili S(O)pRp gdje p je 0, 1, ili 2 i Rp je C1-C6 alkil, C2-C6 alkenil, C2- C6 alkinil, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, ili 5- ili 6-člani heteroaril, i T6 je proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, C1-C6 alkil, hidroksil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, i 5- ili 6-člani heteroaril osim kada T6 je H, halo, hidroksil, ili cijano; ili -Q6-T6 je okso; i R14 je odsutan, H, ili C1-C6 alkil proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, hidroksil, COOH, C(O)O-C1-C6 alkil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di- C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, i 5- ili 6-člani heteroaril.
2. Spoj prema zahtjevu 1, naznačen time da R6 je fenil supstituiran s jednim ili više -Q2- T2; ili Rs je 5- ili 6-člani heteroaril koji sadrži 1-3 dodatnih heteroatoma koji se biraju od N, O, i S i proizvoljno supstituiran s jednim ili više -Q2-T2, poželjno 5- ili 6-člani heteroaril je piridinil, pirazolil, pirimidinil, kinolinil, tetrazolil, oksazolil, izoksazolil, tiazolil, izotiazolil, furil, ili tienil, svaki od kojih je proizvoljno supstituiran s jednim ili više -Q2-T2.
3. Spoj prema bilo kojem od zahtjeva 1-2, naznačen time da T2 je -NRaRb ili - C(O)NRaRb, gdje svaki od Ra i Rb, neovisno je H ili C1-C6 alkil, ili Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore 4 do 12-člani heterocikloalkilni prsten koji ima 0 ili 1 dodatni heteroatom, C1-C6 alkil i 4 do 12-člani heterocikloalkilni prsten koji je proizvoljno supstituiran s jednim ili više -Q3-T3, i Q2 je C1-C3 alkil poveznica proizvoljno supstituirana s halo ili hidroksilom.
4. Spoj prema bilo kojem od zahtjeva 1-3, naznačen time da R7 je C1-C6 alkil, C3-C8 cikloalkil ili 4 do 12-člani heterocikloalkil, svaki proizvoljno supstituiran s jednim ili više -Q5-T5; ili R7 je 4 do 12-člani heterocikloalkil proizvoljno supstituiran s jednim ili više -Q5-T5, poželjno R7 je piperidinil, tetrahidropiran, tetrahidro-2H- tiopiranil,ciklopentil, ili cikloheksil, svaki proizvoljno supstituiran s jednim ili više -Q5-T5.
5. Spoj prema bilo kojem od zahtjeva 1-4, naznačen time da (i) jedan ili više -Q5-T5 su okso; ili (ii) T5 je H, halo, C1-C6 alkil, C1-C6 alkoksil, C3-C8 cikloalkil, C6-C10 aril, ili 4 do 12-člani heterocikloalkil; ili (iii) kada Q5 je veza, T5 je amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C1-C6 alkil, C3-C8 cikloalkil, ili 4 do 12-člani heterocikloalkil; ili (iv) kada Q5 je CO, S(O)2, ili NHC(O), T5 je C1-C6 alkil, C1-C6 alkoksil, C3-C8 cikloalkil, ili 4 do 12-člani heterocikloalkil; ili (v) kada Q5 je C1-C3 alkil poveznica, T5 je H, C6-C10 aril, C3-C8 cikloalkil, 4 do 12-člani heterocikloalkil, ili S(O)qRq.
6. Spoj prema bilo kojem od zahtjeva 1-5, naznačen time da svaki od R1 i R11 je H.
7. Spoj prema bilo kojem od zahtjeva 1-6, naznačen time da svaki od R2 i R4, neovisno je H ili C1-C6 alkil proizvoljno supstituiran s amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, ili C6-C10 aril, poželjno svaki od R2 i R4 je metil.
8. Spoj prema bilo kojem od zahtjeva 1-7, naznačen time da R12 je H, metil, etil, etenil, ili halo, R8is H, metil, ili etil, i R13 je H ili metil.
9. Spoj prema zahtjevu 1, naznačen time da spoj ima Formulu (Ie): [image] poželjno spoj ima Formulu (Ig): [image] pri čemu R2, R4 i R12 su svaki, neovisno C1-6 alkil.
10. Spoj prema bilo kojem od zahtjeva 1 i 9, naznačen time da R6 je C6-C10 aril ili 5- ili 6- člani heteroaril, svaki od kojih je proizvoljno, neovisno supstituiran s jednim ili više - Q2-T2, pri čemu Q2 je veza ili C1-C3 alkil poveznica, i T2 je H, halo, cijano, -ORa, - NRaRb, - (NRaRbRC)+A-, -C(O)NRaRb, -NRbC(O)Ra, -S(O)2R, ili Rs2, gdje svaki od Ra i Rb, neovisno je H ili RS3, svaki od RS2 i RS3, neovisno, je C1-C6 alkil, ili Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore 4 do 7-člani heterocikloalkilni prsten koji ima 0 ili 1 dodatni heteroatom, i svaki od RS2, RS3, i 4 do 7-člani heterocikloalkilni prsten koji tvore Ra i Rb, je proizvoljno, neovisno supstituiran s jednim ili više -Q3-T3, pri čemu Q3 je veza ili C1-C3 alkil poveznica i T3 se bira iz skupine koju čine halo, C1-C6 alkil, 4 do 7-člani heterocikloalkil, ORd, -S(O)2Rd, i - NRdRe, svaki od R i Re neovisno je H ili C1-C6 alkil, ili -Q3-T3 je okso; ili bilo koja dva susjedna -Q2-T2, zajedno s atomima na koje su oni vezani tvore 5- ili 6-člani prsten koji proizvoljno sadrži 1-4 heteroatoma koji se biraju od N, O i S.
11. Spoj prema bilo kojem od zahtjeva 1 i 9, naznačen time da spoj ima Formulu (II): [image] pri čemu Q2 je veza ili metil poveznica,T2 je H, halo, -ORa, -NRaRb, -(NRaRbRC)+A- ili -S(O)2NRaRb, R7 je piperidinil, tetrahidropiran, ciklopentil, ili cikloheksil, svaki proizvoljno supstituiran s one -Q5-T5 i R8 je etil, poželjno spoj ima Formulu (IIa): [image]
12. Spoj prema bilo kojem od zahtjeva 1, 9, i 11, naznačen time da (i) svaki od Ra i Rb, neovisno je H ili C1-C6 alkil proizvoljno supstituiran s jednim ili više -Q3-T3, (ii) jedan od Ra i Rb je H, ili (iii) Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore 4 do 7-člani heterocikloalkilni prsten koji ima 0 ili 1 dodatnih heteroatoma na atomu N i prsten je proizvoljno supstituiran s jednim ili više -Q3-T3, poželjno Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore azetidinil, pirolidinil, imidazolidinil, pirazolidinil, oksazolidinil, izoksazolidinil, triazolidinil, tetrahidrofuranil, piperidinil, 1,2,3,6-tetrahidropiridinil, piperazinil, ili morfolinil, i prsten je proizvoljno supstituiran s jednim ili više -Q3-T3, i više poželjno Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore morfolinil.
13. Spoj prema zahtjevu 1, naznačen time da spoj je odabran od [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] i njihove farmaceutski prihvatljive soli, te je poželjno spoj odabran od [image] [image] [image] [image] [image] [image] [image] i njihove farmaceutski prihvatljive soli.
14. Spoj prema zahtjevu 1, naznačen time da spoj je [image] ili njegova farmaceutski prihvatljiva sol.
15. Farmaceutski pripravak naznačen time da sadrži spoj prema bilo kojem od zahtjeva 114 ili njegovu farmaceutski prihvatljivu sol i farmaceutski prihvatljiv nosač.
16. Spoj prema bilo kojem od zahtjeva 1-14 naznačen time da je za upotrebu u postupku liječenja ili sprječavanja raka.
HRP20161115TT 2011-04-13 2016-09-01 Aril- ili heteroaril-supstituirani spojevi benzena HRP20161115T1 (hr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201161474821P 2011-04-13 2011-04-13
US201161499595P 2011-06-21 2011-06-21
EP12719529.5A EP2697199B1 (en) 2011-04-13 2012-04-13 Aryl-or heteroaryl-substituted benzene compounds
PCT/US2012/033648 WO2012142504A1 (en) 2011-04-13 2012-04-13 Aryl-or heteroaryl-substituted benzene compounds

Publications (1)

Publication Number Publication Date
HRP20161115T1 true HRP20161115T1 (hr) 2016-11-18

Family

ID=46045109

Family Applications (3)

Application Number Title Priority Date Filing Date
HRP20211297TT HRP20211297T8 (hr) 2011-04-13 2012-04-13 Aril- ili heteroaril-supstituirani benzenovi spojevi
HRP20161115TT HRP20161115T1 (hr) 2011-04-13 2016-09-01 Aril- ili heteroaril-supstituirani spojevi benzena
HRP20190074TT HRP20190074T1 (hr) 2011-04-13 2019-01-11 Aril-ili heteroaril-supstituirani spojevi benzena

Family Applications Before (1)

Application Number Title Priority Date Filing Date
HRP20211297TT HRP20211297T8 (hr) 2011-04-13 2012-04-13 Aril- ili heteroaril-supstituirani benzenovi spojevi

Family Applications After (1)

Application Number Title Priority Date Filing Date
HRP20190074TT HRP20190074T1 (hr) 2011-04-13 2019-01-11 Aril-ili heteroaril-supstituirani spojevi benzena

Country Status (36)

Country Link
US (14) US8410088B2 (hr)
EP (5) EP3486234B1 (hr)
JP (6) JP5933686B2 (hr)
KR (7) KR20230134128A (hr)
CN (2) CN107311921B (hr)
AR (1) AR086008A1 (hr)
AU (1) AU2012242595B2 (hr)
BR (2) BR112013026324B1 (hr)
CA (2) CA2832843C (hr)
CL (1) CL2013002898A1 (hr)
CY (3) CY1117986T1 (hr)
DK (4) DK2697199T3 (hr)
ES (4) ES2886099T3 (hr)
FI (1) FI3943485T3 (hr)
HK (1) HK1193804A1 (hr)
HR (3) HRP20211297T8 (hr)
HU (4) HUE042788T2 (hr)
IL (3) IL228745A (hr)
JO (2) JO3438B1 (hr)
LT (4) LT2697199T (hr)
ME (1) ME02500B (hr)
MX (2) MX343685B (hr)
MY (1) MY166171A (hr)
NZ (3) NZ616298A (hr)
PE (1) PE20140863A1 (hr)
PH (1) PH12016502132A1 (hr)
PL (4) PL3943485T3 (hr)
PT (4) PT3486234T (hr)
RS (3) RS55113B1 (hr)
RU (1) RU2632193C2 (hr)
SG (1) SG194447A1 (hr)
SI (4) SI3150580T1 (hr)
SM (1) SMT201600308B (hr)
TW (1) TWI529162B (hr)
WO (1) WO2012142504A1 (hr)
ZA (1) ZA201307539B (hr)

Families Citing this family (109)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130102477A1 (en) 2010-06-23 2013-04-25 Ryan D. Morin Biomarkers for non-hodgkin lymphomas and uses thereof
US9175331B2 (en) * 2010-09-10 2015-11-03 Epizyme, Inc. Inhibitors of human EZH2, and methods of use thereof
CA3176977A1 (en) 2010-09-10 2012-03-15 Epizyme, Inc. Inhibitors of human ezh2, and methods of use thereof
JO3438B1 (ar) 2011-04-13 2019-10-20 Epizyme Inc مركبات بنزين مستبدلة بأريل أو أريل غير متجانس
TW201733984A (zh) * 2011-04-13 2017-10-01 雅酶股份有限公司 經取代之苯化合物
KR20140082742A (ko) 2011-09-30 2014-07-02 글락소스미스클라인 엘엘씨 암을 치료하는 방법
WO2013075084A1 (en) 2011-11-18 2013-05-23 Constellation Pharmaceuticals Modulators of methyl modifying enzymes, compositions and uses thereof
EP2812001B1 (en) 2012-02-10 2017-06-14 Constellation Pharmaceuticals, Inc. Modulators of methyl modifying enzymes, compositions and uses thereof
CA2867282C (en) * 2012-03-12 2024-04-02 Epizyme, Inc. Inhibitors of human ezh2, and methods of use thereof
IL308807A (en) * 2012-04-13 2024-01-01 Epizyme Inc Combined treatment for cancer
SI3184523T1 (sl) * 2012-04-13 2020-04-30 Epizyme Inc N-((4,6 dimetil-2-okso-L,2-dihidropiridin-3-IL)metil)-5-(etil (tetrahidro-2H-piran-4-IL)amino)-4-metil-4'-(morfolinometil)-(L, 1'- bifen IL)-3-karboksamid hidrobromid za uporabo pri zdravljenju celične proliferativne motnje hematološkega sistema
US9562041B2 (en) 2012-05-16 2017-02-07 Glaxosmithkline Llc Enhancer of zeste homolog 2 inhibitors
US20150239842A1 (en) * 2012-09-28 2015-08-27 Pfizer Inc. Benzamide and heterobenzamide compounds
EP3725314A1 (en) 2012-10-15 2020-10-21 Epizyme, Inc. Substituted benzene compounds
MX2015004771A (es) * 2012-10-15 2016-01-08 Epizyme Inc Metodos para tratar cancer.
EP2931707A4 (en) 2012-12-13 2016-07-20 Glaxosmithkline Llc AMPLIFIER OF ZEST HOMOLOG 2 INHIBITORS
WO2014100080A1 (en) * 2012-12-19 2014-06-26 Glaxosmithkline Llc Combination
EP2935264B1 (en) 2012-12-21 2017-10-18 Epizyme, Inc. 1,4-pyridone bicyclic heteroaryl compounds
UA111305C2 (uk) 2012-12-21 2016-04-11 Пфайзер Інк. Конденсовані лактами арилу та гетероарилу
WO2014100646A1 (en) 2012-12-21 2014-06-26 Epizyme, Inc. 1,4-pyridone compounds
TWI629273B (zh) * 2013-02-11 2018-07-11 美商星宿藥物公司 甲基修飾酵素之調節劑、其組成物及用途
WO2014153214A1 (en) 2013-03-14 2014-09-25 Epizyme, Inc. Arginine methyl transferase inhibtors and uses thereof
WO2014178954A1 (en) 2013-03-14 2014-11-06 Epizyme, Inc. Pyrazole derivatives as arginine methyltransferase inhibitors and uses thereof
US9447079B2 (en) 2013-03-14 2016-09-20 Epizyme, Inc. PRMT1 inhibitors and uses thereof
EP2970131B1 (en) 2013-03-14 2017-11-15 Epizyme, Inc. Arginine methyltransferase inhibitors and uses thereof
US9120757B2 (en) 2013-03-14 2015-09-01 Epizyme, Inc. Arginine methyltransferase inhibitors and uses thereof
EP2970181B1 (en) 2013-03-14 2017-06-07 Epizyme, Inc. Arginine methyltransferase inhibitors and uses thereof
EP2970135B1 (en) 2013-03-14 2018-07-18 Epizyme, Inc. Pyrazole derivatives as prmt1 inhibitors and uses thereof
JP6581076B2 (ja) 2013-03-14 2019-09-25 エピザイム，インコーポレイティド アルギニンメチルトランスフェラーゼ阻害剤およびその使用
JP2016516046A (ja) 2013-03-14 2016-06-02 ジェネンテック， インコーポレイテッド がんの治療方法及びがん薬物耐性を阻止する方法
US20160039767A1 (en) 2013-03-14 2016-02-11 Epizyme, Inc. Pyrazole derivatives as prmt1 inhibitors and uses thereof
US9394258B2 (en) 2013-03-14 2016-07-19 Epizyme, Inc. Arginine methyltransferase inhibitors and uses thereof
WO2014151142A1 (en) 2013-03-15 2014-09-25 Constellation Pharmaceuticals, Inc. Modulators of methyl modifying enzymes, compositions and uses thereof
EP2970281A4 (en) 2013-03-15 2016-08-03 Epizyme Inc SUBSTITUTED BENZENE COMPOUNDS
US9243001B2 (en) 2013-03-15 2016-01-26 Epizyme, Inc. Substituted benzene compounds
US9505745B2 (en) 2013-04-30 2016-11-29 Glaxosmithkline Intellectual Property (No. 2) Limited Enhancer of zeste homolog 2 inhibitors
AU2014276417B2 (en) * 2013-06-06 2016-11-24 Glaxosmithkline Intellectual Property (No.2) Limited Enhancer of Zeste Homolog 2 inhibitors
RU2016104044A (ru) 2013-07-10 2017-08-15 Глэксосмитклайн Интеллекчуал Проперти (Nо.2) Лимитед Ингибиторы усилителя zeste гомолога 2
WO2015010078A2 (en) 2013-07-19 2015-01-22 Epizyme, Inc. Substituted 6,5-fused bicyclic heteroaryl compounds
US10150764B2 (en) 2013-07-19 2018-12-11 Epizyme, Inc. Substituted benzene compounds
US9969716B2 (en) 2013-08-15 2018-05-15 Constellation Pharmaceuticals, Inc. Indole derivatives as modulators of methyl modifying enzymes, compositions and uses thereof
HUE063984T2 (hu) * 2013-10-16 2024-02-28 Epizyme Inc Hidroklorid só forma az EZH2 gátlásához
US9738630B2 (en) 2013-11-19 2017-08-22 Bristol-Myers Squibb Company Inhibitors of lysine methyl transferase
WO2015077194A1 (en) * 2013-11-22 2015-05-28 Bristol-Myers Squibb Company Inhibitors of lysine methyl transferase
US20160303135A1 (en) 2013-12-06 2016-10-20 Epizyme, Inc. Combination therapy for treating cancer
CN105037360B (zh) * 2014-04-28 2016-08-17 四川大学 吡啶酮衍生物及其制备方法和用途
SG10201811128RA (en) 2014-06-17 2019-01-30 Epizyme Inc Ezh2 inhibitors for treating lymphoma
PL3157915T3 (pl) 2014-06-17 2019-07-31 Pfizer Inc. Podstawione związki dihydroizochinolinonowe
WO2015200650A1 (en) 2014-06-25 2015-12-30 Epizyme, Inc. Substituted benzene and 6,5-fused bicyclic heteroaryl compounds
WO2016061507A1 (en) 2014-10-16 2016-04-21 Epizyme, Inc. Method for treating cancer
MA40848A (fr) * 2014-10-28 2021-05-05 Glaxosmithkline Ip No 2 Ltd Inhibiteurs d'ezh2 (enhancer of zeste homolog 2)
US11236082B2 (en) 2014-11-06 2022-02-01 Dana-Farber Cancer Institute, Inc. EZH2 inhibitors and uses thereof
CN107249591B (zh) 2014-11-17 2024-01-30 Epizyme股份有限公司 固体药物配制品及其制备方法
AR102767A1 (es) 2014-12-05 2017-03-22 Lilly Co Eli Inhibidores de ezh2
SG10201902664RA (en) 2015-04-20 2019-04-29 Epizyme Inc Combination therapy for treating cancer
AU2016275051A1 (en) 2015-06-10 2017-12-07 Epizyme, Inc. EZH2 inhibitors for treating lymphoma
UY36758A (es) * 2015-06-30 2016-12-30 Glaxosmithkline Ip No 2 Ltd Inhibidores del potenciador del homólogo zeste 2
JP2018525414A (ja) 2015-08-24 2018-09-06 エピザイム，インコーポレイティド 癌を処置するための方法
TW201718598A (zh) 2015-08-27 2017-06-01 美國禮來大藥廠 Ｅｚｈ２抑制劑
WO2017040190A1 (en) 2015-08-28 2017-03-09 Constellation Pharmaceuticals, Inc. Crystalline forms of (r)-n-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1h-indole-3-carboxamide
AU2016333982A1 (en) * 2015-10-06 2018-04-26 Epizyme, Inc. Method of treating medulloblastoma with an EZH2 inhibitor
US20190070188A1 (en) * 2015-11-06 2019-03-07 Epizyme, Inc. Pediatric dosing for treatment of cancer with an ezh2 inhibitor
PT3378859T (pt) 2015-11-19 2019-12-11 Jiangsu Hengrui Medicine Co Derivado de benzofurano, método de preparação do mesmo e uso do mesmo em medicina
CN105440023A (zh) * 2015-12-10 2016-03-30 江苏理工学院 Epz-6438的合成方法
US12084472B2 (en) 2015-12-18 2024-09-10 Ardelyx, Inc. Substituted 4-phenyl pyridine compounds as non-systemic TGR5 agonists
TWI773657B (zh) 2015-12-18 2022-08-11 美商亞德利克斯公司 作爲非全身ｔｇｒ５促效劑之經取代之4-苯基吡啶化合物
WO2017132518A1 (en) 2016-01-29 2017-08-03 Epizyme, Inc. Combination therapy for treating cancer
IL261721B (en) 2016-03-15 2022-07-01 Oryzon Genomics Sa Combinations of lsd1 inhibitors for use in the treatment of solid tumors
WO2017174023A1 (zh) * 2016-04-08 2017-10-12 南京明德新药研发股份有限公司 作为ezh2抑制剂的联苯化合物
JP7493304B2 (ja) * 2016-04-22 2024-05-31 ダナ－ファーバー キャンサー インスティテュート， インコーポレイテッド Ｅｚｈ２インヒビターおよびそれらの使用
WO2017192290A1 (en) 2016-05-04 2017-11-09 The Wistar Institute Of Anatomy And Biology Methods of treating cancers overexpressing carm1 with ezh2 inhibitors and platinum-based antineoplastic drugs
SG11201809560QA (en) 2016-05-05 2018-11-29 Glaxosmithkline Ip No 2 Ltd Enhancer of zeste homolog 2 inhibitors
EP3464643A4 (en) 2016-06-01 2020-04-01 Epizyme Inc USE OF EZH2 INHIBITORS FOR THE TREATMENT OF CANCER
US11147819B2 (en) 2016-06-17 2021-10-19 Epizyme, Inc. EZH2 inhibitors for treating cancer
CA3039059A1 (en) 2016-10-19 2018-04-26 Constellation Pharmaceuticals, Inc. Synthesis of inhibitors of ezh2
EP3548032A2 (en) 2016-12-02 2019-10-09 Epizyme, Inc. Combination therapy for treating cancer
US11191741B2 (en) 2016-12-24 2021-12-07 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide
CN108314677B (zh) 2017-01-17 2020-06-30 安徽中科拓苒药物科学研究有限公司 一种ezh2抑制剂及其用途
TW201831181A (zh) 2017-01-19 2018-09-01 日商第一三共股份有限公司 用以用於治療ｈｔｌｖ－１相關脊髓病之醫藥組成物
US11214561B2 (en) 2017-01-25 2022-01-04 Ancureall Pharmaceutical (Shanghai) Co., Ltd. Histone methyltransferase EZH2 inhibitor, preparation method and pharmaceutical use thereof
US10266542B2 (en) 2017-03-15 2019-04-23 Mirati Therapeutics, Inc. EZH2 inhibitors
US11642346B2 (en) 2017-03-31 2023-05-09 Epizyme, Inc. Combination therapy for treating cancer
CA3060416A1 (en) * 2017-04-21 2018-10-25 Epizyme, Inc. Combination therapies with ehmt2 inhibitors
JP7257328B2 (ja) 2017-05-18 2023-04-13 ジエンス ヘンルイ メデイシンカンパニー リミテッド ベンゾフラン誘導体遊離塩基の結晶およびその製造方法
CN110944628A (zh) 2017-06-02 2020-03-31 Epizyme股份有限公司 使用ezh2抑制剂治疗癌症
WO2018231973A1 (en) 2017-06-13 2018-12-20 Epizyme, Inc. Inhibitors of ezh2 and methods of use thereof
JP7399079B2 (ja) * 2017-09-05 2023-12-15 エピザイム，インコーポレイティド 癌を処置するための併用療法
BR112020008325A2 (pt) 2017-11-14 2020-10-20 Pfizer Inc. terapias de combinação com o inibidor de ezh2
DK3746446T3 (da) 2018-01-31 2022-06-27 Mirati Therapeutics Inc PRC2-inhibitorer
CN108640842B (zh) * 2018-04-04 2021-06-04 大连九信精细化工有限公司 一种2-溴-5-氟硝基苯的合成方法
CN116375907A (zh) 2018-06-07 2023-07-04 默沙东有限责任公司 用于制备舒更葡糖的方法
WO2020011607A1 (en) 2018-07-09 2020-01-16 Fondation Asile Des Aveugles Inhibition of prc2 subunits to treat eye disorders
WO2020020374A1 (zh) * 2018-07-27 2020-01-30 苏州信诺维医药科技有限公司 多取代苯环化合物、制备方法及其用途
KR102689665B1 (ko) 2019-02-19 2024-07-31 한미약품 주식회사 신규한 헤테로트리시클릭 유도체 화합물 및 이의 용도
WO2020192650A1 (zh) * 2019-03-25 2020-10-01 上海华汇拓医药科技有限公司 酰胺类化合物制备方法及其在医药领域的应用
CN114555112A (zh) 2019-08-22 2022-05-27 朱诺治疗学股份有限公司 T细胞疗法和zeste增强子同源物2(ezh2)抑制剂的组合疗法及相关方法
WO2021249305A1 (zh) * 2020-06-08 2021-12-16 南京明德新药研发有限公司 联苯类化合物
AU2021359475A1 (en) * 2020-10-13 2023-06-15 Evopoint Biosciences Co., Ltd. Crystal form of multi-substituted benzene ring compound maleate, and preparation method therefor and use thereof
CN114907299B (zh) * 2021-02-08 2024-06-25 上海医药工业研究院 他泽司他关键中间体的盐型、其制备方法及其中间体
CN114907300B (zh) * 2021-02-08 2024-05-28 上海医药工业研究院 他泽司他关键中间体的制备方法及其中间体
CN113292489B (zh) * 2021-06-16 2022-08-30 泓博智源(开原)药业有限公司 二氯代二烷基烟腈的制备方法
CN113527275A (zh) * 2021-07-20 2021-10-22 成都师范学院 一种sklb1039化合物及其制备方法和应用
CN113582863B (zh) * 2021-08-19 2023-05-26 沈阳农业大学 一种氨乙基联苯类化合物及其制备方法和用途
KR20230081459A (ko) 2021-11-30 2023-06-07 엘젠테라퓨틱스 주식회사 헤테로사이클릭이 치환된 신규한 3-페닐피리딘과 4-페닐피리딘 유도체 및 이의 용도
WO2023111810A1 (en) 2021-12-14 2023-06-22 Pfizer Inc. Combination therapies and uses for treating cancer
AU2023262308A1 (en) 2022-04-27 2024-10-03 Astrazeneca Uk Limited Combination of antibody-drug conjugate with ezh1 and/or ezh2 inhibitor
WO2023244918A1 (en) 2022-06-13 2023-12-21 Treeline Biosciences, Inc. Quinolone bcl6 bifunctional degraders
TW202415655A (zh) 2022-06-13 2024-04-16 美商樹線生物科學公司 １，８—萘啶—２—酮異雙功能ｂｃｌ６降解劑
CN115197202B (zh) * 2022-07-15 2024-01-26 四川大学 一种ezh2共价抑制剂及其制备方法和应用

Family Cites Families (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
JPH0733729A (ja) 1993-07-26 1995-02-03 Kirin Brewery Co Ltd Ｎ−シアノ−ｎ′−置換−アリールカルボキシイミダミド化合物の製造法
CA2155662A1 (en) * 1993-12-27 1995-07-06 Fumihiro Ozaki Anthranilic acid derivative
DE19516776A1 (de) 1995-05-10 1996-11-14 Boehringer Ingelheim Int Chromatin-Regulatorgene
US5741819A (en) 1995-06-07 1998-04-21 3-Dimensional Pharmaceuticals, Inc. Arylsulfonylaminobenzene derivatives and the use thereof as factor Xa inhibitors
US5763263A (en) 1995-11-27 1998-06-09 Dehlinger; Peter J. Method and apparatus for producing position addressable combinatorial libraries
JP3906935B2 (ja) 1995-12-18 2007-04-18 杏林製薬株式会社 Ｎ−置換ジオキソチアゾリジルベンズアミド誘導体及びその製造法
AU6060099A (en) 1998-09-30 2000-04-17 Procter & Gamble Company, The 2-substituted ketoamides
UA71587C2 (uk) 1998-11-10 2004-12-15 Шерінг Акцієнгезелльшафт Аміди антранілової кислоти та їхнє застосування як лікарських засобів
US6710058B2 (en) 2000-11-06 2004-03-23 Bristol-Myers Squibb Pharma Company Monocyclic or bicyclic carbocycles and heterocycles as factor Xa inhibitors
JP4137636B2 (ja) 2000-12-28 2008-08-20 塩野義製薬株式会社 カンナビノイド２型受容体親和作用を有するピリドン誘導体
EP1363702A4 (en) * 2001-01-30 2007-08-22 Cytopia Pty Ltd PROCESS FOR INHIBITING KINASES
US7700293B2 (en) 2001-08-02 2010-04-20 The Regents Of The University Of Michigan Expression profile of prostate cancer
ES2421511T3 (es) 2001-12-21 2013-09-03 X Ceptor Therapeutics Inc Moduladores de LXR
PT1477186E (pt) 2002-02-19 2010-02-11 Shionogi & Co Antipruriginosos
TW200306155A (en) 2002-03-19 2003-11-16 Du Pont Benzamides and advantageous compositions thereof for use as fungicides
ES2591252T3 (es) 2002-12-27 2016-11-25 Sucampo Ag Derivados de prostaglandinas para tratar el síndrome de colon irritable y/o la dispepsia funcional
JP4695588B2 (ja) * 2003-02-26 2011-06-08 スージェン， インク． プロテインキナーゼ阻害剤としてのアミノヘテロアリール化合物
WO2005014599A1 (en) * 2003-06-04 2005-02-17 Cellular Genomics, Inc. Imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of bruton’s tyrosine kinase by such compounds
US7442685B2 (en) 2003-06-13 2008-10-28 The University Of North Carolina At Chapel Hill DOT1 histone methyltransferases as a target for identifying therapeutic agents for leukemia
US7560467B2 (en) 2003-06-19 2009-07-14 Smithkline Beecham Corporation Indazolo-tetrahydropyrimidine-carboxamide derivative kinase inhibitors
ME00294B (me) * 2003-07-23 2011-05-10 Bayer Pharmaceuticals Corp Fluoro supstituisana omega-karaboksiaril difenil urea za liječenje i prevenciju bolesti i stanja bolesti
PT1663194E (pt) 2003-08-26 2010-07-06 Merck Hdac Res Llc Utilizaã†o de saha para o tratamento de mesotelioma
US20050059682A1 (en) 2003-09-12 2005-03-17 Supergen, Inc., A Delaware Corporation Compositions and methods for treatment of cancer
CA2558545C (en) 2004-03-11 2012-10-16 Actelion Pharmaceuticals Ltd Indol-1-yl-acetic acid derivatives
CN1286973C (zh) 2004-04-12 2006-11-29 上海第二医科大学附属瑞金医院 一种组蛋白甲基转移酶及其制备方法
WO2005118796A2 (en) 2004-06-01 2005-12-15 The University Of North Carolina At Chapel Hill Reconstituted histone methyltransferase complex and methods of identifying modulators thereof
JO2787B1 (en) 2005-04-27 2014-03-15 امجين إنك, Alternative amide derivatives and methods of use
DE602006019423D1 (de) 2005-06-02 2011-02-17 Univ North Carolina Reinigung, charakterisierung und wiederherstellung einer ubiquitin-e3-ligase
FR2889526B1 (fr) 2005-08-04 2012-02-17 Aventis Pharma Sa 7-aza-indazoles substitues, compositions les contenant, procede de fabrication et utilisation
PE20110285A1 (es) 2005-10-19 2011-06-04 Gruenenthal Chemie Derivados de sulfonamidofenil propionamida como ligandos del receptor vaniloide del subtipo 1
BRPI0617655A2 (pt) 2005-10-21 2016-08-23 Merck & Co Inc composto ou um sal farmaceuticamente aceitável do mesmo, ou um isômero óptico do mesmo, uso de um composto, e, formulação farmacêutica
US20090203057A1 (en) 2005-10-28 2009-08-13 Yi Zhang Protein demethylases comprising a jmjc domain
EP1960551A2 (en) 2005-12-01 2008-08-27 Medical Prognosis Institute Methods and devices for identifying biomarkers of treatment response and use thereof to predict treatment efficacy
WO2007070818A1 (en) 2005-12-14 2007-06-21 Bristol-Myers Squibb Company Six-membered heterocycles useful as serine protease inhibitors
EP1974055A4 (en) 2006-01-20 2010-01-27 Univ North Carolina DIAGNOSTIC AND THERAPEUTIC OBJECTIVES AGAINST LEUKEMIA
AU2007333021A1 (en) 2006-05-15 2008-06-19 Irm Llc Terephthalamate compounds and compositions, and their use as HIV integrase inhibitors
WO2007136592A2 (en) 2006-05-18 2007-11-29 Amphora Discovery Corporation 2-0x0-l,2-dihydr0quin0line derivatives, compositions, and uses thereof as antiproliferative agents
JP2010505958A (ja) 2006-10-10 2010-02-25 バーンハム インスティトゥート フォー メディカル リサーチ 神経防護作用組成物および方法
US8314087B2 (en) 2007-02-16 2012-11-20 Amgen Inc. Nitrogen-containing heterocyclyl ketones and methods of use
US8338437B2 (en) 2007-02-28 2012-12-25 Methylgene Inc. Amines as small molecule inhibitors
WO2008109534A1 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting ezh2 gene expression and uses thereof
WO2008113006A1 (en) 2007-03-14 2008-09-18 Xenon Pharmaceuticals Inc. Methods of using quinolinone compounds in treating sodium channel-mediated diseases or conditions
DE102007017884A1 (de) 2007-04-13 2008-10-16 Grünethal GmbH Neue Vanilloid-Rezeptor Liganden und ihre Verwendung zur Herstellung von Arzneimitteln
US20090012031A1 (en) 2007-07-03 2009-01-08 The Regents Of The University Of Michigan EZH2 Cancer Markers
ES2457418T3 (es) 2007-07-16 2014-04-25 Abbvie Inc. Indazoles, bencisoxazoles y bencisotiazoles como inhibidores de proteína cinasas
CA2703909A1 (en) * 2007-10-31 2009-05-07 Merck Sharp & Dohme Corp. P2x3, receptor antagonists for treatment of pain
EA019974B1 (ru) 2007-12-19 2014-07-30 Кансер Рисерч Текнолоджи Лимитед 8-ЗАМЕЩЕННЫЕ ПИРИДО[2,3-b]ПИРАЗИНЫ И ИХ ПРИМЕНЕНИЕ
EP2235001B1 (en) * 2008-01-23 2014-12-24 Bristol-Myers Squibb Company Process for preparing pyridinone compounds
WO2009124137A2 (en) 2008-04-01 2009-10-08 Mount Sinai School Of Medicine Of New York University Method of suppressing gene transcription through histone lysine methylation
US20100113415A1 (en) * 2008-05-29 2010-05-06 Rajapakse Hemaka A Epha4 rtk inhibitors for treatment of neurological and neurodegenerative disorders and cancer
UY31982A (es) * 2008-07-16 2010-02-26 Boehringer Ingelheim Int Derivados de 1,2-dihidropiridin-3-carboxamidas n-sustituidas
AU2009279616A1 (en) 2008-08-08 2010-02-11 New York Blood Center Small molecule inhibitors of retroviral assembly and maturation
FR2934995B1 (fr) 2008-08-14 2010-08-27 Sanofi Aventis Composes d'azetidines polysubstitues, leur preparation et leur application en therapeutique
US20120208809A1 (en) * 2009-03-24 2012-08-16 Sanofi 9h-pyrrolo[2,3-b: 5,4-c'] dipyridine azacarboline derivatives, preparation thereof, and therapeutic use thereof
WO2010111653A2 (en) 2009-03-27 2010-09-30 The Uab Research Foundation Modulating ires-mediated translation
WO2011011366A2 (en) 2009-07-20 2011-01-27 Constellation Pharmaceuticals Agents for stimulating activity of methyl modifying enzymes and methods of use thereof
CA2784899A1 (en) 2009-12-30 2011-07-07 Avon Products, Inc. Topical lightening composition and uses thereof
US8637509B2 (en) * 2010-05-07 2014-01-28 Glaxosmithkline Llc Azaindazoles
UA110112C2 (uk) * 2010-05-07 2015-11-25 Глаксосмітклайн Ллс Індоли
ES2534804T3 (es) 2010-05-07 2015-04-28 Glaxosmithkline Llc Indazoles
US20130102477A1 (en) 2010-06-23 2013-04-25 Ryan D. Morin Biomarkers for non-hodgkin lymphomas and uses thereof
US9175331B2 (en) 2010-09-10 2015-11-03 Epizyme, Inc. Inhibitors of human EZH2, and methods of use thereof
CA3176977A1 (en) 2010-09-10 2012-03-15 Epizyme, Inc. Inhibitors of human ezh2, and methods of use thereof
WO2012068589A2 (en) 2010-11-19 2012-05-24 Constellation Pharmaceuticals Modulators of methyl modifying enzymes, compositions and uses thereof
WO2012075080A1 (en) 2010-12-01 2012-06-07 Glaxosmithkline Llc Indoles
AU2011336272A1 (en) 2010-12-03 2013-06-20 Epizyme, Inc. 7-deazapurine modulators of histone methyltransferase, and methods of use thereof
WO2012118812A2 (en) 2011-02-28 2012-09-07 Epizyme, Inc. Substituted 6,5-fused bicyclic heteroaryl compounds
TW201733984A (zh) 2011-04-13 2017-10-01 雅酶股份有限公司 經取代之苯化合物
JO3438B1 (ar) 2011-04-13 2019-10-20 Epizyme Inc مركبات بنزين مستبدلة بأريل أو أريل غير متجانس
KR20140082742A (ko) 2011-09-30 2014-07-02 글락소스미스클라인 엘엘씨 암을 치료하는 방법
CA2867282C (en) * 2012-03-12 2024-04-02 Epizyme, Inc. Inhibitors of human ezh2, and methods of use thereof
IL308807A (en) 2012-04-13 2024-01-01 Epizyme Inc Combined treatment for cancer
SI3184523T1 (sl) 2012-04-13 2020-04-30 Epizyme Inc N-((4,6 dimetil-2-okso-L,2-dihidropiridin-3-IL)metil)-5-(etil (tetrahidro-2H-piran-4-IL)amino)-4-metil-4'-(morfolinometil)-(L, 1'- bifen IL)-3-karboksamid hidrobromid za uporabo pri zdravljenju celične proliferativne motnje hematološkega sistema
US9562041B2 (en) 2012-05-16 2017-02-07 Glaxosmithkline Llc Enhancer of zeste homolog 2 inhibitors
EP3725314A1 (en) 2012-10-15 2020-10-21 Epizyme, Inc. Substituted benzene compounds
MX2015004771A (es) 2012-10-15 2016-01-08 Epizyme Inc Metodos para tratar cancer.

Also Published As

Publication number Publication date
KR20190025055A (ko) 2019-03-08
US20160022693A1 (en) 2016-01-28
CN104080769B (zh) 2017-06-20
RS62279B1 (sr) 2021-09-30
US20120264734A1 (en) 2012-10-18
MX343685B (es) 2016-11-17
EP4360712A2 (en) 2024-05-01
MX2013011921A (es) 2014-03-27
PL2697199T3 (pl) 2016-12-30
US20240277723A1 (en) 2024-08-22
JP2023011933A (ja) 2023-01-24
KR20230134128A (ko) 2023-09-20
PH12016502132A1 (en) 2017-05-22
US20240245698A1 (en) 2024-07-25
EP3150580A1 (en) 2017-04-05
LT2697199T (lt) 2016-09-26
KR20210118968A (ko) 2021-10-01
JOP20180104A1 (ar) 2019-01-30
BR122020006541B1 (pt) 2022-05-10
AU2012242595B2 (en) 2014-05-15
LT3486234T (lt) 2021-09-10
ZA201307539B (en) 2014-06-25
JO3438B1 (ar) 2019-10-20
RU2013150345A (ru) 2015-05-20
EP3150580B1 (en) 2018-10-17
CA3086473A1 (en) 2012-10-18
HUE042788T2 (hu) 2019-07-29
US10155002B2 (en) 2018-12-18
SMT201600308B (it) 2016-11-10
SI3150580T1 (sl) 2019-03-29
CY1117986T1 (el) 2017-05-17
US10420775B2 (en) 2019-09-24
US9090562B2 (en) 2015-07-28
US20180318309A1 (en) 2018-11-08
PL3486234T3 (pl) 2021-11-29
CN107311921A (zh) 2017-11-03
IL266418A (en) 2019-06-30
US20140288041A1 (en) 2014-09-25
US9549931B2 (en) 2017-01-24
DK3943485T3 (da) 2024-01-22
HUE056552T2 (hu) 2022-02-28
KR20190121386A (ko) 2019-10-25
NZ717119A (en) 2017-10-27
JP6778226B2 (ja) 2020-10-28
KR102032303B1 (ko) 2019-10-15
HUE066461T2 (hu) 2024-08-28
EP3943485B1 (en) 2023-12-27
PE20140863A1 (es) 2014-07-19
FI3943485T3 (fi) 2024-01-29
KR102566864B1 (ko) 2023-08-11
PL3943485T3 (pl) 2024-05-20
US20130123234A1 (en) 2013-05-16
ES2589555T3 (es) 2016-11-15
ME02500B (me) 2017-02-20
US9855275B2 (en) 2018-01-02
KR20200105543A (ko) 2020-09-07
US20150353494A1 (en) 2015-12-10
HK1193804A1 (zh) 2014-10-03
PT2697199T (pt) 2016-09-05
DK3486234T3 (da) 2021-08-16
US11052093B2 (en) 2021-07-06
JO3363B1 (ar) 2019-03-13
EP4360712A3 (en) 2024-07-31
JP2016147886A (ja) 2016-08-18
AU2012242595A1 (en) 2013-05-02
PT3150580T (pt) 2019-01-28
HRP20211297T8 (hr) 2022-02-18
LT3943485T (lt) 2024-02-12
TW201302704A (zh) 2013-01-16
US9522152B2 (en) 2016-12-20
RU2632193C2 (ru) 2017-10-03
KR101955871B1 (ko) 2019-03-08
US20210379076A1 (en) 2021-12-09
US20240245697A1 (en) 2024-07-25
LT3150580T (lt) 2019-02-11
EP3943485A1 (en) 2022-01-26
CL2013002898A1 (es) 2014-08-22
EP2697199B1 (en) 2016-06-08
BR112013026324A8 (pt) 2018-01-30
MX2020012695A (es) 2021-04-12
BR112013026324A2 (pt) 2016-10-11
JP2021042243A (ja) 2021-03-18
PL3150580T3 (pl) 2019-04-30
HUE028837T2 (en) 2017-01-30
KR102308488B1 (ko) 2021-10-06
HRP20211297T1 (hr) 2021-12-10
CY1121120T1 (el) 2019-12-11
ES2973868T3 (es) 2024-06-24
RS58226B1 (sr) 2019-03-29
KR101914321B1 (ko) 2018-11-02
JP2014516931A (ja) 2014-07-17
HRP20190074T1 (hr) 2019-03-08
RU2017132054A3 (hr) 2021-05-14
JP2018104450A (ja) 2018-07-05
JP5933686B2 (ja) 2016-06-15
US20170119780A1 (en) 2017-05-04
KR20140029442A (ko) 2014-03-10
WO2012142504A1 (en) 2012-10-18
IL228745A0 (en) 2013-12-31
JP2019014732A (ja) 2019-01-31
SI3486234T1 (sl) 2021-12-31
PT3943485T (pt) 2024-03-06
EP3486234B1 (en) 2021-06-02
EP2697199A1 (en) 2014-02-19
KR20180120275A (ko) 2018-11-05
US8765732B2 (en) 2014-07-01
IL228745A (en) 2016-12-29
TWI529162B (zh) 2016-04-11
IL249273B (en) 2019-05-30
US20200155562A1 (en) 2020-05-21
CN107311921B (zh) 2021-02-12
DK3150580T3 (en) 2019-02-04
IL249273A0 (en) 2017-01-31
MY166171A (en) 2018-06-07
NZ616298A (en) 2016-03-31
PT3486234T (pt) 2021-09-07
BR112013026324B1 (pt) 2020-12-08
SI3943485T1 (sl) 2024-04-30
CN104080769A (zh) 2014-10-01
ES2706951T3 (es) 2019-04-01
NZ734744A (en) 2019-03-29
CA2832843C (en) 2020-09-29
ES2886099T3 (es) 2021-12-16
US20170252349A1 (en) 2017-09-07
RU2017132054A (ru) 2019-02-06
AR086008A1 (es) 2013-11-13
US20190192526A1 (en) 2019-06-27
DK2697199T3 (en) 2016-09-12
CA2832843A1 (en) 2012-10-18
SG194447A1 (en) 2013-12-30
SI2697199T1 (sl) 2016-10-28
KR102154946B1 (ko) 2020-09-10
CY1124617T1 (el) 2022-07-22
US8410088B2 (en) 2013-04-02
EP3486234A1 (en) 2019-05-22
RS55113B1 (sr) 2016-12-30

Similar Documents

Publication Publication Date Title
HRP20161115T1 (hr) Aril- ili heteroaril-supstituirani spojevi benzena
JP2018104450A5 (hr)
HRP20181048T1 (hr) Neuroaktivni 19-alkoksi-17-supstituirani steroidi, korisni u postupcima liječenja
HRP20191901T1 (hr) Ciklizirani derivati sulfamoilarilamida i njihova uporaba kao lijekova za liječenje hepatitisa b
AR081830A1 (es) Activadores de guanilato ciclasa soluble, composiciones farmaceuticas que los comprenden y sus usos
HRP20160623T1 (hr) Inhibitori proteinske kinaze
HRP20230162T1 (hr) Heteroarilni inhibitori enzima pde4
AR102361A1 (es) Compuestos de metil-quinolina útiles para inhibir la sintasa-1 de prostaglandina microsomal e2
RS54480B1 (en) IMIDAZOPYRIDASINE AS ACT KINASE INHIBITORS
HRP20160655T1 (hr) Supstituirani spojevi purina i 7-deazapurina kao modulatori epigenetskih enzima
AR092062A1 (es) Modificador de sabor dulce
RU2016135922A (ru) Терапевтические соединения и композиции
HRP20190888T1 (hr) Konjugat antitijela za igf-ir i lijeka i njegova upotreba u liječenju karcinoma
HRP20180196T1 (hr) Diketoni i hidroksiketoni kao aktivatori puta signalizacije katenina
CR20150056A (es) Derivados de azaindol
AR100714A1 (es) Derivados de alquilo y arilo de compuestos de 1-oxa-4,9-diazaespiro undecano que tienen actividad multimodal contra el dolor
HRP20230215T1 (hr) Supstituirani policiklički derivati piridona i njihov predlijek
WO2016089758A3 (en) Organo-1-oxa-4-azonium cyclohexane compounds
AR069185A1 (es) Compuestos heterociclicos moduladores de gamma secretasa, composiciones farmaceuticas que los contienen y usos de los mismos para tratar trastornos del snc, tales como enfermedad de alzheimer y otras relacionadas con la deposicion de proteinas amiloides.
JP2016511753A5 (hr)
HRP20230233T1 (hr) Inhibitori pirazola magl
HRP20241020T1 (hr) Makrociklički spoj koji služi kao wee1 inhibitor i njegove primjene
HRP20210066T1 (hr) Proces pripreme spoja indol karboksamida
PE20200664A1 (es) Compuestos espirociclicos y sus metodos de preparacion y uso
HRP20160523T1 (hr) Antikancerozni steroidni laktoni, nezasićeni na položaju 7(8)