KR101178233B1 - 2-4-Subsituted-1,4-diazepan-1-ylacetamide compounds having activity for T-type calcium channel - Google Patents

Abstract

The present invention comprises a 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound having activity against a T-type calcium channel, a method for preparing the compound, and the compound as an active ingredient. It relates to a pharmaceutical composition. The novel 2- (4-substituted-1,4-diazepan-1-yl) acetamide compounds or pharmaceutically acceptable salts thereof of the present invention have an antagonistic action against T-type calcium channels, and thus, epilepsy, hypertension, etc. It is useful as an agent for treating brain diseases, treatment for heart diseases such as angina pectoris, treatment for pain diseases such as chronic pain, neuropathic pain, or anticancer agents.

Description

2- (4-substituted-1,4-diazepan-1-yl) acetamide compound having activity against T-type calcium channel {2- (4-Subsituted-1,4-diazepan-1-yl) acetamide compounds having activity for T-type calcium channel}

The present invention comprises a 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound having activity against a T-type calcium channel, a method for preparing the compound, and the compound as an active ingredient. It relates to a pharmaceutical composition. The novel 2- (4-substituted-1,4-diazepan-1-yl) acetamide compounds or pharmaceutically acceptable salts thereof of the present invention have an antagonistic action against T-type calcium channels, and thus, epilepsy, hypertension, etc. It is useful as a treatment for brain diseases, treatment for heart diseases such as angina pectoris, treatment for pain diseases such as chronic pain and neuropathic pain, or as an anticancer agent.

Calcium channels play an important role in intracellular signal transduction by increasing the concentration of calcium by stimulation of nerve cells. The calcium channel is divided into a high-voltage activated calcium channel and a low-voltage activated calcium channel. A representative low voltage activated calcium channel is a T-type calcium channel.

T-type calcium channels are present in the central muscles, adrenal glands, isotopes, and the heart, and antagonists of T-type calcium channels are known to be effective in treating brain diseases such as epilepsy and hypertension and heart diseases such as angina. [1) Hosravani, Houman et al., "Effects of Cav3.2 channel mutations linked to idiopathic generalized epilepsy", Annals of Neurology (2005), 57 (5) , 745-749; 2) Vitko, Iuliia et al., "Functional characterization and neuronal modeling of the effects of childhood absence epilepsy variants of CACNA1H, a T-type calcium channel", Journal of Neuroscience (2005), 25 (19) , 4844-4855; 3) Clozel, Cardiovas Drugs Ther . (1990), 4 , pp. 731-736; 4) Hefti, Arzneimittel forschung (1990), 40 , 417-421; 5) Moosmang, Sven et al., "Antihypertensive Effects of the Putative T-Type Calcium Channel Antagonist Mibefradil Are Mediated by the L-Type Calcium Channel Cav1.2", Circulation Research (2006), 98 (1) , 105-110 ]

Recently, antagonists of T-type calcium channels have been shown to be effective in treating chronic pain [ Drugs of the Future (2005), 40 , 573-580], and spinal nerve ligation in a1G knock-out mice. It has been reported that nerve pain can be relieved as a result of causing spinal nerve ligation. [ Molecules & Cells , 2008, 25 , 242-246] In addition, mibefradil and ethosuximide as antagonists of T-type calcium channels induce mechanical and thermal in animal models of spinal nerve ligation. The degree of inhibition was reported to be dependent on the drug dose, indicating that antagonists of T-type calcium channels are effective in treating neurological pain. [ Pain , 2003, 105 , 159-168]

Other reports suggest that calcium is known to be involved in cell growth, suggesting that antagonists of T-type calcium channels may have anticancer effects. Nat. Rev. Mol. Cell Biol. 2003 , 4 , 517-529]

Mibefradil, a commercially available antagonist of T-type calcium channels, was used to treat hypertension and angina, but mibepradil was banned due to its interaction with various other drugs. There is an urgent need for the development of antagonists of T-type calcium channels. To date, there have been many efforts to develop antagonists of T-type calcium channels, but the antagonists of selective T-type calcium channels are not well known.

As described above, the antagonist of T-type calcium channel is effective as an anti-cancer agent for treating brain diseases such as epilepsy and hypertension, for treating heart diseases such as angina pectoris, for treating chronic pain, neuropathic pain, etc. Ham has already been revealed in several papers. It is also a new T-type calcium channel that is selective for T-type calcium channels, has a good pharmacokinetic profile, good ADME (absorption, distribution, metabolism, and excretion) and is effective in heart disease, cancer, epilepsy, neurological pain and related diseases. Antagonist development is required.

An object of the present invention is to provide a 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound having a novel structure.

The present invention includes a novel 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound or a pharmaceutically acceptable salt as an active ingredient and has a selective antagonism against T-type calcium channel. It is another object to provide a pharmaceutical composition.

The present invention includes a novel 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound or a pharmaceutically acceptable salt as an active ingredient for treating brain diseases such as epilepsy and hypertension, angina pectoris and the like. It is another object of the present invention to provide a therapeutic agent for pain diseases such as heart disease, chronic pain, neuropathic pain, or an anticancer agent.

In order to realize the above object, the present invention provides a 2- (4-substituted-1,4-diazepane-1-yl) acetamide compound represented by the following Chemical Formula 1 showing selective antagonistic activity on T-type calcium channel And a method for producing the compound and a pharmaceutical composition containing the compound.

In Formula 1,

n is 0, 1, 2, or 3,

R ¹ is a C ₁ to C ₆ alkyl group in which 1 to 3 substituents selected from phenyl and halophenyl are substituted or unsubstituted; Or a 5 to 10 membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O and S, or a heterocyclic group, wherein the heteroaryl group is selected from halo, C ₁ to C ₆ alkyl and phenyl 1 to 3 substituents selected may be substituted or unsubstituted,

R ² and R ³ are the same as or different from each other and are a hydrogen atom; Or 1 to 3 substituents selected from halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy and C ₁ -C ₆ haloalkyl are substituted or unsubstituted phenyl groups; Or R ² and R ³ represent a 5-10 membered heterocycloalkyl group formed by bonding to each other including nitrogen atoms alone, or 1 to 3 heteroatoms selected from N, O and S to which they are bonded, or hetero The cycloalkyl group may be substituted or unsubstituted with 1 to 3 substituents selected from halo, C ₁ to C ₆ alkyl, and phenyl.

Since the 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound of the present invention or a pharmaceutically acceptable salt thereof has an antagonistic action against T-type calcium channel, such as epilepsy, hypertension, etc. It is useful as an agent for treating brain diseases, treatment for heart diseases such as angina pectoris, treatment for pain diseases such as chronic pain and neuropathic pain, or anticancer agents.

Pharmaceutically acceptable salts of the 2- (4-substituted-1,4-diazepane-1-yl) acetamide compound represented by Formula 1 include, for example, metal salts, salts with organic bases, inorganic acids, Salts, salts with organic acids, salts with basic or acidic amino acids, and the like. Suitable metal salts include, for example, alkali metal salts such as sodium salts, potassium salts and the like; Alkaline earth metal salts such as calcium salts, magnesium salts, barium salts and the like; Aluminum salts and the like. Salts with organic bases are, for example, trimethylamine, triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N Salts with , N -dibenzylethylenediamine and the like. Salts with inorganic acids may include, for example, salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like. Salts with organic acids may include, for example, salts with formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, p -toluenesulfonic acid, and the like. . Salts with basic amino acids may include, for example, salts with arginine, lysine, ornithine and the like. Salts with acidic amino acids may include, for example, salts with aspartic acid, glutamic acid and the like.

The substituents used in the definition of the 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound represented by Chemical Formula 1 according to the present invention will be described in more detail as follows.

'Halo' or 'halogen' is used interchangeably with each other, and means the elements fluoro, chloro, bromo, iodo. 'Alkyl group' includes all linear, pulverized and cyclic carbon chains having 1 to 6 carbon atoms, with preferred alkyl groups being methyl, ethyl, n -propyl, isopropyl, n -butyl and isobutyl Groups , tert -butyl groups, neopentyl groups, cyclopentyl groups, 3,3-dimethylbutyl groups, cyclohexyl groups and the like. 'Haloalkyl group' includes 1 to 13 halogen atoms such as fluoro, chloro, bromo and iodo, and includes all linear, pulverized and cyclic carbon chains having 1 to 6 carbon atoms, and preferred halo. The alkyl group includes a fluoromethyl, trifluoromethyl, 1,2-dichloroethyl group, 1,1-dichloroethyl group, pentafluoroethyl group and the like. "Alkoxy group" means an alkyl group of carbon connected to oxygen, wherein alkyl is as defined above. "Heteroaryl group" includes 5 to 10 atoms of aromatic heterohydrocarbon group in the form of a monocyclic or conjugated ring containing one or more preferably 1 to 4 heteroatoms selected from N, O and S. The heteroaryl groups described above may specifically be pyrrolyl, furyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxdiazolyl, thidiazolyl, tetrazolyl, Pyridinyl, pyrazinyl, triazinyl, pyridazinyl, pyrimidinyl, triazolyl, indolyl, indolinyl, isoindolyl, benzofuryl, benzofurazanyl, dibenzofuryl, isobenzofuryl, indazolyl, Benzoimidazolyl, imidazopyridinyl, benzooxazolyl, benzoisoxazolyl, benzothiazolyl, dibenzothiophenyl, naphthyridyl, benzoisothiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, fr Thalazinyl, chinolinyl, quinazolinyl, carbazolyl, phenazinyl, phenthiathiazinyl, acridinyl, and the like. The heteroaryl group may be substituted with one or more substituents selected from halo, C ₁ -C ₆ alkyl, amine, C ₁ -C ₆ alkylamino, phenyl and the like. 'Heterocycloalkyl group' is an aliphatic heterohydrocarbon group having 5 to 10 carbon atoms containing 1 to 4 heteroatoms selected from N, O, and S, consisting of a single ring, a bicyclic ring, or a cyclic ring, which may include an unsaturated carbon chain. Include. The heterocycle group is specifically tetrahydrofuryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, morpholino, piperazinyl, pyrrolidinoneyl, piperidinyl, isoindoledioneyl, dioxanyl, Dioxoranyl, benzodioxyyl, chromanyl and the like.

In the 2- (4-substituted-1,4-diazepane-1-yl) acetamide compound represented by Formula 1, preferably n is 0, 1, 2, or 3; R ¹ is a methyl group, ethyl group, n -propyl group, isopropyl group, n -butyl group, isobutyl group, tert -butyl group, neopentyl group, 3,3-dimethylbutyl group, benzyl group, (4-fluoro Rophenyl) methyl group, diphenylmethyl group, or di (4-fluorophenyl) methyl group, or oxazolyl group, benzooxazolyl group, thiazolyl group, benzothiazolyl group, imidazolyl group, and benzoimidazolyl A heteroaryl group selected from the group, wherein the heteroaryl group is substituted with 1 to 3 substituents selected from fluoro, chloro, methyl, ethyl, n -propyl, isopropyl, n -butyl, isobutyl, tert -butyl, and phenyl Or can be unsubstituted; R ² and R ³ are the same as or different from each other and are a hydrogen atom or fluoro, chloro, methyl, ethyl, n -propyl, isopropyl, n -butyl, isobutyl, tert -butyl, methoxy, ethoxy, One to three substituents selected from trifluoromethyl and dichloroethyl are substituted or unsubstituted phenyl groups, or represent heterocycloalkyl groups selected from piperidinyl groups, piperazinyl groups, and morpholinyl groups, wherein the heterocycloalkyl groups are fluoro As such, 1-3 substituents selected from chloro, methyl, ethyl, n -propyl, isopropyl, n -butyl, isobutyl, tert -butyl, phenyl, and benzyl may be substituted or unsubstituted.

In the 2- (4-substituted-1,4-diazepane-1-yl) acetamide compound represented by Formula 1, more preferably n is 0 or 1; R ¹ is isopropyl group, tert -butyl group, (4-fluorophenyl) methyl group, diphenylmethyl group, di (4-fluorophenyl) methyl group, thiazol-2-yl group, 4-methylthiazole-2 -Yl group, 4-phenyl-5-propylthiazol-2-yl group, benzothiazol-2-yl group, 6-fluorobenzothiazol-2-yl group, 1H -imidazol-2-yl group, 2-phenyl -1 H - imidazol-2-yl group, 1 H - benzo [d] imidazol-2-yl group, oxazol-2-yl group, 4-phenyl-5-propyl-oxazol-2-yl group, 4,5- A dimethyloxazol-2-yl group, a benzo [ d ] oxazol-2-yl group, a 6-fluorobenzo [ d ] oxazol-2-yl group, or a 6-methylbenzo [ d ] oxazol-2-yl group. ; R ² and R ³ are the same as or different from each other and are a hydrogen atom, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2- Methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2,3-dimethylphenyl group, 2,4-dimethylphenyl group, 2,5-dimethylphenyl group, 2,6-dimethylphenyl group, 3,4-dimethylphenyl group, 2, 3-diethylphenyl group, 2,4-diethylphenyl group, 2,5-diethylphenyl group, 2,6-diethylphenyl group, 3,4-diethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2- (trifluoromethyl) phenyl group, 3- (trifluoromethyl) phenyl group, or 4- (trifluoromethyl) phenyl group, or R ² and R ³ to which they are bonded Piperidinyl, 4-methylpiperidinyl, 2-ethylpiperidinyl, 4-benzylpiperidinyl, piperazinyl, 4-methylpiperazinyl, or morpholino groups formed by bonding to nitrogen atoms together To me Is the art compounds.

Particularly preferred examples of the 2- (4-substituted-1,4-diazepane-1-yl) acetamide compound represented by Formula 1 above are as follows:

N- (2,6-diethylphenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

N- (2,4-dimethylphenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

N- (3,4-dimethylphenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

N- (2,6-dimethylphenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

N- (2-chlorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

N- (3-chlorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

N- (4-chlorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

N- (2-fluorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

N- (3-fluorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

N- (4-fluorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) -N - o -tolylacetamide;

2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) -N - m -tolylacetamide;

2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) -N - p -tolylacetamide;

N- (2-methoxyphenyl) -2- (4-thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

N- (3-methoxyphenyl) -2- (4-thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

N- (4-methoxyphenyl) -2- (4-thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;

2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide;

2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide;

2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide;

N- (2,6-diethylphenyl) -2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2,4-dimethylphenyl) -2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3,4-dimethylphenyl) -2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2,6-dimethylphenyl) -2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-fluorophenyl) acetamide;

2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3-fluorophenyl) acetamide;

2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4-fluorophenyl) acetamide;

N- (2-chlorophenyl) -2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3-chlorophenyl) -2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide;

N- (4-chlorophenyl) -2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide;

2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide;

2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide;

2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide;

2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-methoxyphenyl) acetamide;

2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide;

2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- methoxyphenyl) acetamide;

2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide;

2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide;

2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2,6- diethyl-phenyl) acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl-methyl)) -1,4-diazepan-1-yl) - N - (2,4- dimethyl-phenyl) -acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl-methyl)) -1,4-diazepan-1-yl) - N - (3,4- dimethyl-phenyl) -acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl-methyl)) -1,4-diazepan-1-yl) - N - (2,6- dimethyl-phenyl) -acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-fluorophenyl) acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3-fluorophenyl) acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4-fluorophenyl) acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl-methyl)) -1,4-diazepan-1-yl) - N - (2- chlorophenyl) acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl-methyl)) -1,4-diazepan-1-yl) - N - (3- chlorophenyl) acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- chlorophenyl) acetamide;

2- (4-(( 1H -benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - o -tolylacetamide;

2- (4-(( 1H -benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - m -tolylacetamide;

2- (4-(( 1H -benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - p -tolylacetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl-methyl)) -1,4-diazepan-1-yl) - N - (2- methoxyphenyl) acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl-methyl)) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- methoxyphenyl) acetamide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide Amide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - acetamide (methyl) phenyl 3- (trifluoromethyl) Amide;

2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - acetamide (methyl) phenyl-4- (trifluoromethyl) Amide;

N- (2,6-diethylphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2,6-dimethylphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3,4-dimethylphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2,4-dimethylphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2-chlorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3-chlorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (4-chlorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2-fluorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3-fluorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (4-fluorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide;

2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide;

2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide;

N- (2-methoxyphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3-methoxyphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (4-methoxyphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

2- (4 - ((4-phenyl-5-propyl-oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide Amide;

2- (4 - ((4-phenyl-5-propyl-oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide Amide;

2- (4 - ((4-phenyl-5-propyl-oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide Amide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (2,6- diethyl-phenyl) acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2,4- dimethyl-phenyl) -acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3,4- dimethyl-phenyl) -acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2,6- dimethyl-phenyl) -acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- chlorophenyl) acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- chlorophenyl) acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- chlorophenyl) acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (2-fluorophenyl) acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (3-fluorophenyl) acetamide;

2- (4 - ((1 H - il-imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (4-fluorophenyl) acetamide;

2- (4-(( 1H -imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - o -tolylacetamide;

2- (4-(( 1H -imidazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide;

2- (4-(( 1H -imidazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (2- methoxyphenyl) acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (3- methoxyphenyl) acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (4- methoxyphenyl) acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - methyl (2- (trifluoromethyl) phenyl acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide;

2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide;

N- (2,6-diethylphenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2,4-dimethylphenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3,4-dimethylphenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2,6-dimethylphenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2-chlorophenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide;

N- (3-chlorophenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide;

N- (4-chlorophenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide;

2- (4 - ((4,5-Dimethyl-2-yl) methyl) diazepan-1-yl) - N - (2-fluorophenyl) acetamide;

2- (4 - ((4,5-Dimethyl-2-yl) methyl) diazepan-1-yl) - N - (3-fluorophenyl) acetamide;

2- (4 - ((4,5-Dimethyl-2-yl) methyl) diazepan-1-yl) - N - (4-fluorophenyl) acetamide;

2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide;

2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide;

2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide;

2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-methoxyphenyl) acetamide;

2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide;

2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- methoxyphenyl) acetamide;

2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide;

2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide;

2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide;

N- (2,6-diethylphenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide ;

N- (2,4-dimethylphenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3,4-dimethylphenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2,6-dimethylphenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2-chlorophenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3-chlorophenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (4-chlorophenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-fluorophenyl) acetamide;

2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3-fluorophenyl) acetamide;

2- (4 - ((6-fluoro-benzo [d] oxazol-2- yl) methyl) -1,4-diazepan-1-yl) - N - (4-fluorophenyl) acetamide;

2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - o -tolylacetamide;

2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide;

2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - p -tolylacetamide;

2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-methoxyphenyl) acetamide;

2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide;

2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- methoxyphenyl) acetamide;

2- (4 - ((benzo [d] oxazol-2-yl) 6-fluoro-methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) Acetamide;

2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) Acetamide;

2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) Acetamide;

N- (2,6-diethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2,4-dimethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3,4-dimethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2,6-dimethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2-chlorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3-chlorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (4-chlorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2-fluorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3-fluorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (4-fluorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) -N - o -tolylacetamide;

2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) -N - m -tolylacetamide;

2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) -N - p -tolylacetamide;

N- (2-methoxyphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-azpan-1-yl) acetamide;

N- (3-methoxyphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (4-methoxyphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;

2- (4 - ((2-phenyl -1 H-imidazol-5-yl) methyl) -1,4-diazepan-1-yl) - N-acetamido (methyl) phenyl-2- (trifluoromethyl) Amide;

2- (4 - ((2-phenyl -1 H-imidazol-5-yl) methyl) -1,4-diazepan-1-yl) - N-acetamido (methyl) phenyl 3- (trifluoromethyl) Amide;

2- (4 - ((2-phenyl -1 H-imidazol-5-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide Amide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2,6- diethyl-phenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2,4- dimethyl-phenyl) -acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (3,4- dimethyl-phenyl) -acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2,6- dimethyl-phenyl) -acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2-chlorophenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (3- chlorophenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (4-chlorophenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2-fluorophenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (3-fluorophenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (4-fluorophenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2-methoxyphenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (4-methoxyphenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide;

2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide;

N- (2,4-dimethylphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3,4-dimethylphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2,6-dimethylphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2-chlorophenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3-chlorophenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (4-chlorophenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2-fluorophenyl) -2- (4-(((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3-fluorophenyl) -2- (4-(((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (4-fluorophenyl) -2- (4-(((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide;

2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide;

2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide;

N- (2-methoxyphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3-methoxyphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (4-methoxyphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

2- (4 - ((6-methylbenzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide Amide;

2- (4 - ((6-methylbenzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide Amide;

2- (4 - ((6-methylbenzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide Amide;

N- (2,6-diethylphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (3-chlorophenyl) -2- (4-neopentyl-1,4-diazepan-1-yl) acetamide;

N- (3-chlorophenyl) -2- (4- (3,3-dimethylbutyl) -1,4-diazepan-1-yl) acetamide;

2- (4-(( 1H -benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -1- (piperidin-1-yl) ethanone;

2- (4-(( 1H -benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -1-morpholinoethanone;

2- (4-(( 1H -Benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -1- (4-methylpiperidin-1-yl) Ethanone;

2- (4-(( 1H -benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -1- (2-ethylpiperidin-1-yl) Ethanone;

2- (4-(( 1H -benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -1- (4-benzylpiperidin-1-yl) Ethanone;

N- (2-fluorophenyl) -2- (4-((4-phenyl-5-propylthiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;

N- (2,6-diethylphenyl) -2- (4- (4-methylthiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide; And

Pharmaceutically acceptable salts thereof.

On the other hand, the present invention includes a method for preparing the 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound represented by Chemical Formula 1. The preparation method of the present invention comprises a two step process, as shown in Schemes 1 and 2.

The first production method of the present invention, as shown in Scheme 1 below,

Iii) reacting the chloroamide compound represented by the following formula (2) with the 1,4-diazepane represented by the following formula (3) to obtain the (1,4-diazepan-1-yl) acetamide compound represented by the following formula (4) Manufacturing process; And

Ii) reacting the (1,4-diazepan-1-yl) acetamide compound represented by the following formula (4) with the aldehyde compound represented by the following formula (5a) or the halide compound represented by the following formula (5b), Preparing a 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound; It is made, including.

[Reaction Scheme 1]

In Scheme 1, n, R ¹ , R ² , and R ³ are each as defined in Chemical Formula 1, and X represents a halogen atom.

Iii) process according to Scheme 1 is carried out by a coupling reaction between the chloro compound and the 1,4-diazephan compound.

In addition, the process ii) may be performed by reductive amination with an aldehyde compound represented by Chemical Formula 5a as an alkylation reaction or by a coupling reaction with a halide compound represented by Chemical Formula 5b.

The second production method of the present invention, as shown in Scheme 2 below,

Iii) preparing an aldehyde compound represented by the following Formula 5a or a halide compound represented by the following Formula 5b by using the R ¹ substituted 1,4-diazepane compound represented by Formula 6; And

Ii) Reacting the R ¹ substituted 1,4-diazepane compound represented by Formula 6 with a chloroamide compound represented by Formula 2 below, yields 2- (4-substituted-1,4 represented by Formula 1 Preparing diazepan-1-yl) acetamide compound; .

Scheme 2

In Scheme 2, n, R ¹ , R ² , and R ³ are each as defined in Chemical Formula 1, and X represents a halogen atom.

The process iii) according to Scheme 2 may be performed by reductive amination with an aldehyde compound represented by Chemical Formula 5a as an alkylation reaction or by a coupling reaction with a halide compound represented by Chemical Formula 5b. Can be.

And, step ii) is performed by the coupling reaction between the chloro compound and the 1,4-diazephan compound.

Reductive amination reaction to be carried out in the scheme 1 and 2 is carried out in the presence of a reducing agent. In the reaction, molecular sieves (molecular sieve, 4 A, beads, 4-8 mesh) were used. As the reducing agent, NaBH (OAc) ₃ , NaBH ₃ CN, NaBH _4, etc. may be used. The amount of the reducing agent is slightly different depending on the reactivity, and is about 2 to 10 equivalents, preferably NaBH (OAc) ₃ 2 to 4 Use equivalents. The reaction temperature is about 20 ℃ to 50 ℃, the reaction can be carried out smoothly even around room temperature.

In addition, the coupling reaction performed in Schemes 1 and 2 may be performed under conditions using an appropriate binder and an organic solvent. Examples of the binder include inorganic bases such as carbonates, sulfates, and hydroxides of alkali or alkaline earth metals, or mono (C ₁ -C ₅ alkyl) amines, di (C ₁ -C ₅ alkyl) amines, and tri (C ₁ -C ₅ alkyls). Organic bases, such as an amine, etc. can be used, Preferably ethyl diisopropylamine (EDIPA) is used. The reaction temperature can be carried out in the reflux temperature range of -30 ℃ to the solvent used, more specifically in the temperature range of room temperature to 120 ℃, more specifically can be carried out in the temperature range of 30 ℃ to 80 ℃.

The solvent used in the reductive amination reaction and the coupling reaction described above may be an inert organic solvent which does not affect the reaction as an organic solvent commonly used in the art. Specific examples of the organic solvent that can be used in the present invention include lower alcohols having 1 to 6 carbon atoms such as diethyl ether, methanol, ethanol and propanol, ethers such as tetrahydrofuran, or halogenated hydrocarbons such as chloroform and dichloromethane. Nitriles such as acetonitrile, amides such as N, N -dimethylformamide (DMF), and the like can be used. Preferably, dichloromethane, N, N -dimethylformamide (DMF) is used.

In addition, the chloroamide compound represented by Chemical Formula 2, the aldehyde compound represented by Chemical Formula 5a, and the halide compound represented by Chemical Formula 5b used as raw materials in the preparation method according to Scheme 1 are known compounds. You can purchase and use the products on sale.

On the other hand, the present invention includes a pharmaceutical composition comprising a 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient. .

The pharmaceutical composition of the present invention is suitable for oral or parenteral administration by formulating in a conventional formulation method including other conventional carriers, adjuvants or diluents together with the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof. It may be prepared in the form. In the case of oral administration, it may be prepared in the form of tablets, capsules, solutions, syrups, suspensions, etc., and in the case of parenteral administration, it may be prepared in the form of injections for intraperitoneal, subcutaneous, muscle, and transdermal.

The effective daily dose of T-type calcium channel antagonist of the pharmaceutical composition of the present invention is 0.01 to 1000 mg / day based on an adult, but the dosage is the age, weight, sex, dosage form, health condition and disease level of the patient. Depending on the judgment of the doctor or pharmacist may be divided doses once a day to several times a day.

Accordingly, the present invention provides a pharmaceutical use of the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition containing the same for the purpose of treating and preventing a disease.

That is, the present invention has an activity against T-type calcium channels, and thus diseases treatable by T-type calcium channel antagonism, such as brain diseases such as epilepsy and hypertension, heart diseases such as angina pectoris, chronic pain, and neuropathy It includes medicinal uses used for the treatment of pain diseases such as pain or cancer diseases.

The present invention as described above will be described in more detail through the following Examples and Experimental Examples, but the present invention is not limited to these Examples and Experimental Examples.

[Example]

Representative Synthesis Examples below show representative synthesis examples of 2- (4-substituted-1,4-diazepan-1-yl) acetamide compounds represented by Chemical Formula 1 according to the present invention, The expert can easily synthesize the desired compound based on the following typical synthesis examples or through modification.

Representative Synthesis Example 1. Synthesis of 2-chloro- N- (2,6-dimethylphenyl) acetamide (Formula 2)

2,6-dimethylaniline (2.0 g, 16.5 mmol) and chloroacetyl chloride (1.45 mL, 18.2 mmol) were added to 40 mL of dichloromethane, followed by stirring at room temperature to obtain 2.2 g (68%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 7.85 (bs, 1H), 7.17-7.09 (m, 3H), 4.24 (s, 2H), 2.25 (s, 6H)

Representative Synthetic Example 2 2- (1,4-diazepan-1-yl) - N - (2,6- dimethyl-phenyl) -acetamide Synthesis of (IV)

To 40 mL of N, N -dimethylformamide, 2-chloro- N- (2,6-dimethylphenyl) acetamide (Formula 2; 1.83 g, 9.26 mmol) and 1,4-diazepane (Formula 3; 91.39 g) , 13.8 mmol) and ethyl diisopropylamine (EDIPA; 18.5 mmol) were added and stirred to obtain the target compound (yield 52%).

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.84 (br, 1H), 7.12-7.10 (m, 3H), 3.33 (s, 2H), 3.00-2.87 (m, 8H), 2.23 (s, 6H), 2.19 (bs, 1 H), 1.88 (m, 2 H).

Representative Synthesis Example 3 of N- (2,6-diethylphenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide (Formula 1) synthesis

In dichloromethane 2- (1,4-diazepan-1-yl) - N - (2,6- diethyl-phenyl) acetamide (formula 4; 150 mg, 0.52 mmol) were dissolved, NaBH (OAc) ₃ ( 253 mg, 1.19 mmol) and a molecular sieve were added thereto, and then thiazole-2-carbaaldehyde (Formula 5a) was added dropwise. Stirring was carried out for about 20 minutes to obtain 101 mg (66%) of the target compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.83 (bs, 1H), 7.71 (d, 1, J = 3.30 Hz), 7.28-7.12 (m, 4H), 4.04 (s, 2H), 3.91 (s, 2H), 3.39 (s, 2H), 3.01-2.88 (m, 8H), 2.59 (q, 4H, J = 7.57 Hz), 1.96-1.90 (m, 2H), 1.19 (t, 6H, J = 5.82 Hz ).

Representative Synthesis Example 4. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2,6- diethyl Synthesis of Phenyl) acetamide (Formula 1)

N, N - dimethylformamide, 2- (chloromethyl) -1 H - benzoimidazole (Formula 5b; 60 mg, 0.36 mmol) and 2- (1,4-diazepan-1-yl) - N - ( 2,6-diethylphenyl) acetamide (Formula 4; 135 mg, 0.47 mmol) and ethyl diisopropylamine (EDIPA; 130 μL, 0.72 mmol) were added and refluxed and stirred at 70 ° C. for 8 hours. 88 mg (58%) of compound were obtained.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.81 (bs, 1H), 7.70 (bs, 2H), 7.25-7.12 (m, 5H), 3.95 (s, 2H), 3.36 (s, 2H), 2.96- 2.82 (m, 8H), 2.59 (q, 4H, J = 7.50 Hz), 1.93-1.86 (m, 2H), 1.17 (t, 6H, J = 6.37 Hz).

Representative Example 5: Synthesis of 2 - ((1,4-diazepan-1-yl) methyl) -1 H-benzo [d] imidazole-synthesis of the (formula 6)

1,4-diazepane (901 mg, 9 mmol) and EDIPA (1.31 mL) in 2- (chloromethyl) -1 H -benzo [d] imidazole (500 mg, 3.0 mmol) in N, N -dimethylformamide. ) Was added and stirred at 60 ° C for 12 hours to obtain 375 mg (54%) of the target compound.

¹ H NMR (MeOD, 300 MHz) δ 7.56-7.53 (m, 2H), 7.25-7.21 (m, 2H), 3.99 (s, 2H), 3.13-3.06 (m, 4H), 1.95-1.89 (m, 2H)

Representative Synthesis Example 6. 2- (4- ( 1H -Benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -1- (piperidin-1-yl Synthesis of Ethanone (Formula 1)

2-chloro-1- (piperidin-1-yl) ethanone (0.508 mmol), 2-((1,4-diazepane-1-yl) methyl) -1 H in N, N -dimethylformamide -Benzo [ d ] imidazole (0.309 mmol) and EDIPA (0.976 mmol) were added thereto, and the resultant was stirred at 60 ° C for 12 hours to obtain the target compound in 20% yield.

¹ H NMR (MeOD, 400 MHz) δ 7.54-7.52 (m, 2H), 7.27-7.19 (m, 2H), 3.94 (s, 2H), 3.55-3.48 (m, 4H), 3.37 (s, 2H) , 2.84-2.78 (m, 8H), 1.89-1.87 (m, 2H), 1.54-1.

The following examples are examples of the compound represented by Formula 1 synthesized using the above-described representative synthesis example.

Example 1. N - (2,6- diethyl-phenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide (Compound No. 1)

Thiazol-2-aldehyde cover (35 μL, 0.40 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (2,6- diethyl-phenyl) Acetamide (150 mg, 0.52 mmol) and NaBH (OAc) ₃ (253 mg, 1.19 mmol) were used to obtain 101 mg (66%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.83 (bs, 1H), 7.71 (d, 1, J = 3.30 Hz), 7.28-7.12 (m, 4H), 4.04 (s, 2H), 3.91 (s, 2H), 3.39 (s, 2H), 3.01-2.88 (m, 8H), 2.59 (q, 4H, J = 7.57 Hz), 1.96-1.90 (m, 2H), 1.19 (t, 6H, J = 5.82 Hz ).

Example 2. N- (2,4-dimethylphenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepane-1-yl) acetamide (Compound No. 2)

Thiazol-2-aldehyde cover (35 μL, 0.40 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (2,4- dimethylphenyl) acetamide Amide (135 mg, 0.52 mmol) and NaBH (OAc) ₃ (253 mg, 1.19 mmol) were used to obtain 100 mg (70%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.16 (bs, 1H), 7.71 (d, 1, J = 3.28 Hz), 7.36-7.25 (m, 3H), 7.06 (d, 1H, J = 8.07 Hz) , 4.05 (s, 2H), 3.28 (s, 2H), 3.25 (s, 2H), 2.92-2.87 (m, 8H), 2.23 (d, 6H, J = 13.04 Hz), 1.93-1.87 (m, 2H ).

Example 3. N - (3,4- dimethylphenyl) -2- (4- (thiazol-2-yl-methyl) -1,4-diazepan-1 yl) acetamide (Compound No. 3)

Thiazol-2-aldehyde cover (35 μL, 0.40 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (3,4- dimethylphenyl) acetamide Amide (135 mg, 0.52 mmol), NaBH (OAc) ₃ (253 mg, 1.19 mmol) was used to give 87 mg (62%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.76 (bs, 1H), 7.67 (d, 1H, J = 3.30 Hz), 7.25 (d, 1H, J = 3.30 Hz), 7.12-7.02 (m, 3H) , 4.00 (s, 2H), 3.34 (s, 2H), 3.00-2.85 (m, 8H), 2.21 (s, 6H), 1.92-1.86 (m, 2H).

Example 4. N - (2,6- dimethylphenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide (Compound No. 4)

Thiazol-2-aldehyde cover (35 μL, 0.40 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (2,6- dimethylphenyl) acetamide Amide (135 mg, 0.52 mmol), NaBH (OAc) ₃ (253 mg, 1.19 mmol) was used to give 96 mg (67%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.22 (bs, 1H), 7.92 (d, 1H, J = 8.10 Hz), 7.67 (d, 1H, J = 2.36 Hz), 7.26 (dd, 1H, J = 0.98, 3.24 Hz), 7.00-6.93 (m, 2H), 4.00 (s, 2H), 3.28 (s, 2H), 2.91-2.85 (m, 8H), 2.24 (d, 6H, J = 10.28 Hz), 1.91-1.84 (m, 2 H).

Example 5. N - (2- chloro-phenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide (Compound No. 5)

Thiazole-2-carbaaldehyde (50 μL, 0.57 mmol), N- (2-chlorophenyl) -2- (1,4-diazepane-1-yl) acetamide in the same manner as in Synthesis Example 3 198 mg, 7.40 mmol) and NaBH (OAc) ₃ (362 mg, 1.71 mmol) were used to obtain 169 mg (81%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.99 (bs, 1H), 8.46 (d, 1H, J = 8.26 Hz), 7.67 (t, 1H, J = 1.61 Hz), 7.34 (d, 1H, J = 8.03 Hz), 7.25-7.22 (m, 2H), 7.02-6.98 (m, 1H), 6.77 (s, 1H), 4.00 (s, 2H), 3.30 (s, 2H), 2.91-2.78 (m, 8H ), 1.93-1.87 (m, 2H).

Example 6. N - (3- chloro-phenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide (Compound No. 6)

Thiazole-2-carbaaldehyde (50 μL, 0.57 mmol), N- (3-chlorophenyl) -2- (1,4-diazepane-1-yl) acetamide in the same manner as in Synthesis Example 3 198 mg, 7.40 mmol) and NaBH (OAc) ₃ (362 mg, 1.71 mmol) afforded 152 mg (73%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.37 (bs, 1H), 7.71 (d, 1H, J = 3.28 Hz), 7.68 (s, 1H), 7.39 (d, 1H, J = 8.1 Hz), 7.19 (t, 1H, J = 8.0 Hz), 7.02 (d, 1H, J = 8.0 Hz), 7.45 (d, 1H, J = 8.16 Hz), 7.31-7.22 (m, 2H), 7.08-7.06 (m, 1H), 4.06 (s, 2H), 3.32 (s, 2H), 2.91-2.85 (m, 8H), 1.93-1.87 (m, 2H).

Example 7. N - (4-chloro-phenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide (Compound No. 7)

Thiazole-2-carbaaldehyde (50 μL, 0.57 mmol), N- (4-chlorophenyl) -2- (1,4-diazepane-1-yl) acetamide in the same manner as in Synthesis Example 3 198 mg, 7.40 mmol) and NaBH (OAc) ₃ (362 mg, 1.71 mmol) afforded 162 mg (78%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.34 (bs, 1H), 7.70 (d, 1H, J = 3.25 Hz), 7.53 (d, 1H, J = 8.62 Hz), 7.29-7.26 (m, 3H) , 4.04 (s, 2H), 3.28 (s, 2H), 2.93-2.86 (m, 8H), 1.91-1.85 (m, 2H).

Example 8. N - 2- (2- fluorophenyl) (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide (Compound No. 8)

Thiazol-2-aldehyde cover (50 μL, 0.57 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - acetamide (2-fluorophenyl) (186 mg, 0.74 mmol) and NaBH (OAc) ₃ (362 mg, 1.71 mmol) were used to obtain 159 mg (80%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.66 (bs, 1H), 8.37 (t, 1H, J = 6.90 Hz), 7.68 (d, 1H, J = 3.25 Hz), 7.24 (d, 1H, J = 2.11 Hz), 7.13-6.99 (m, 3H), 4.02 (s, 2H), 3.30 (s, 2H), 2.91-2.86 (m, 8H), 1.93-1.87 (m, 2H).

Example 9. N - (3- fluoro-phenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide (Compound No. 9)

Thiazol-2-aldehyde cover (50 μL, 0.57 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - acetamide (3-fluorophenyl) (186 mg, 0.74 mmol) and NaBH (OAc) ₃ (362 mg, 1.71 mmol) were used to obtain 131 mg (66%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.38 (bs, 1H), 7.66 (d, 1H, J = 3.27 Hz), 7.54-7.51 (m, 1H), 7.30-7.16 (m, 3H), 6.77- 6.73 (m, 1H), 4.00 (s, 2H), 3.21 (s, 2H), 2.93-2.79 (m, 8H), 1.89-1.82 (m, 2H).

Example 10. N - (4-fluorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide (Compound No. 10)

Thiazol-2-aldehyde cover (50 μL, 0.57 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (4-fluorophenyl) acetamide (186 mg, 0.74 mmol) and NaBH (OAc) ₃ (362 mg, 1.71 mmol) were used to obtain 159 mg (80%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.33 (bs, 1H), 7.72 (d, 1H, J = 3.23 Hz), 7.58-7.55 (m, 2H), 7.31 (d, 1H, J = 3.22 Hz) , 7.03 (t, 2H, J = 8.48 Hz), 4.08 (s, 2H), 3.32 (s, 2H), 2.94-2.90 (m, 8H), 1.94-1.90 (m, 2H).

Example 11. 2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) -N - o -tolylacetamide (Compound No. 11)

Thiazole-2-carbaaldehyde (35 μL, 0.40 mmol), 2- (1,4-diazepane-1-yl) -N - o -tolylacetamide (128 mg, 0.52 mmol), NaBH (OAc) ₃ (253 mg, 1.19 mmol) gave 82 mg (60%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.34 (bs, 1H), 8.11 (d, 1H, J = 8.04 Hz), 7.68 (t, 1H, J = 3.02 Hz), 7.27 (t, 1H, J = 3.03 Hz), 7.22-7.15 (m, 2H), 7.02 (t, 1H, J = 7.42 Hz), 4.01 (s, 2H), 3.31 (s, 2H), 2.93-2.88 (m, 8H), 2.29 ( s, 3H), 1.92-1.87 (m, 2H).

Example 12. 2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) -N - m -tolylacetamide (Compound No. 12)

Thiazole-2-carbaaldehyde (35 μL, 0.40 mmol), 2- (1,4-diazepane-1-yl) -N - m -tolylacetamide (128 mg, 0.52 mmol), NaBH (OAc) ₃ (253 mg, 1.19 mmol) gave 87 mg (63%) of the title compound.

H NMR (CDCl ₃ , 400 MHz) δ 9.26 (bs, 1H), 7.70 (d, 2H, J = 3.49 Hz), 7.43-7.14 (m, 4H), 6.92 (d, 2H, J = 0.60 Hz), 4.04 (s, 2H), 3.30 (s, 2H), 2.93-2.89 (m, 8H), 2.36 (s, 3H), 1.94-1.89 (m, 2H).

Example 13. 2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) -N - p -tolylacetamide (Compound No. 13)

Thiazole-2-carbaaldehyde (35 μL, 0.40 mmol), 2- (1,4-diazepane-1-yl) -N - p -tolylacetamide (128 mg, 0.52 mmol), NaBH (OAc) ₃ (253 mg, 1.19 mmol) gave 105 mg (77%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.22 (bs, 1H), 7.70 (d, 1H, J = 3.14 Hz), 7.45 (d, 2H, J = 6.85 Hz), 7.28 (d, 1H, J = 3.17 Hz), 7.12 (d, 2H, J = 7.91 Hz), 4.04 (s, 2H), 3.28 (s, 2H), 2.91-2.87 (m, 8H), 2.31 (s, 3H), 1.90-1.86 ( m, 2H).

Example 14 N- (2-methoxyphenyl) -2- (4-thiazol-2-ylmethyl) -1,4-diazepane-1-yl) acetamide (Compound No. 14)

Thiazol-2-aldehyde cover (35 μL, 0.40 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (2-methoxyphenyl) acetamide (136 mg, 0.52 mmol) and NaBH (OAc) ₃ (253 mg, 1.19 mmol) gave 101 mg (70%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.84 (bs, 1H), 8.40 (d, 1H, J = 6.54 Hz), 7.68 (d, 1H, J = 3.27 Hz), 7.26 (dd, 1H, J = 3.29, 0.74 Hz), 7.04-6.86 (m, 3H), 4.00 (s, 2H), 3.88 (s, 3H), 3.25 (s, 2H), 2.93-2.82 (m, 8H), 1.92-1.86 (m , 2H).

Example 15. N - (3- methoxy-phenyl) -2- (4-thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide (Compound No. 15)

Thiazol-2-aldehyde cover (35 μL, 0.40 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide (136 mg, 0.52 mmol) and NaBH (OAc) ₃ (253 mg, 1.19 mmol) gave 101 mg (70%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.27 (bs, 1H), 7.69 (d, 1H, J = 3.30 Hz), 7.36 (t, 1H, J = 2.27 Hz), 7.28 (d, 1H, J = 3.30 Hz), 7.27-6.63 (m, 3H), 4.03 (s, 2H), 3.80 (s, 3H), 3.25 (s, 2H), 2.93-2.83 (m, 8H), 1.94-1.85 (m, 2H ).

Example 16. N - (4-methoxyphenyl) -2- (4-thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide (Compound No. 16)

Thiazol-2-aldehyde cover (35 μL, 0.40 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (4- methoxyphenyl) acetamide (136 mg, 0.52 mmol) and NaBH (OAc) ₃ (253 mg, 1.19 mmol) were used to obtain 99 mg (69%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.20 (bs, 1H), 7.72 (d, 1H, J = 3.29 Hz), 7.50 (dd, 2H, J = 6.91, 2.02 Hz), 7.30 (d, 1H, J = 3.29 Hz), 6.90-6.84 (m, 2H), 4.06 (s, 2H), 3.81 (s, 3H), 3.30 (s, 2H), 2.93-2.82 (m, 8H), 1.94-1.90 (m , 2H).

Example 17. 2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide (Compound No. 17 )

Thiazol-2-aldehyde cover (35 μL, 0.40 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) Phenyl) acetamide (156 mg, 0.52 mmol), NaBH (OAc) ₃ (253 mg, 1.19 mmol) was used to obtain 113 mg (70%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.96 (bs, 1H), 8.42 (d, 1H, J = 8.25 Hz), 7.66 (t, 1H, J = 3.02 Hz), 7.58-7.49 (m, 2H) , 7.27-7.13 (m, 2H), 3.99 (s, 2H), 3.29 (s, 2H), 2.91-2.85 (m, 8H), 1.90-1.85 (m, 2H).

Example 18. 2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide (Compound No. 18 )

Thiazol-2-aldehyde cover (35 μL, 0.40 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) Phenyl) acetamide (156 mg, 0.52 mmol) and NaBH (OAc) ₃ (253 mg, 1.19 mmol) were used to obtain 129 mg (81%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.45 (bs, 1H), 7.84 (s, 1H), 7.78 (d, 1H, J = 8.03 Hz), 7.68 (d, 1H, J = 2.30 Hz), 7.44 -7.20 (m, 2H), 4.03 (s, 2H), 3.29 (s, 2H), 2.90-2.85 (m, 8H), 1.90-1.86 (m, 2H).

Example 19. 2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide (Compound No. 19 )

Thiazol-2-aldehyde cover (35 μL, 0.40 mmol) in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) Phenyl) acetamide (156 mg, 0.52 mmol) and NaBH (OAc) ₃ (253 mg, 1.19 mmol) were used to obtain 121 mg (76%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.55 (bs, 1H), 7.78-7.73 (m, 3H), 7.56 (d, 2H, J = 17.34 Hz), 7.31 (d, 2H, J = 3.30 Hz) , 4.08 (s, 2H), 3.34 (s, 2H), 2.95-2.91 (m, 8H), 1.94-1.83 (m, 2H).

Example 20 N- (2,6-diethylphenyl) -2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepane-1-yl) acet Amide (Compound No. 20)

6-fluoro in the same manner as in Synthesis Example 3 represents benzothiazol-2-carbazole aldehyde (25 mg, 0.13 mmol), 2- (1,4- diazepan-1-yl) - N - (2,6 26 mg (42%) of the title compound were obtained using diethylphenyl) acetamide (53 mg, 0.18 mmol) and NaBH (OAc) ₃ (88 mg, 0.41 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.84 (bs, 1H), 7.88 (q 1H, J = 4.57 Hz), 7.49 (dd, 1H, J = 8.16, 2.56 Hz), 7.25-7.13 (m, 4H ), 4.09 (s, 2H), 3.41 (s, 2H), 3.04-2.92 (m, 8H), 2.59 (q, 4H, J = 7.56 Hz), 1.99-1.93 (m, 2H), 1.19 (t, 6H, J = 7.57 Hz).

Example 21. N - (2,4- dimethylphenyl) -2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound No. 21)

6-fluoro in the same manner as in Synthesis Example 3 represents benzothiazol-2-carbazole aldehyde (25 mg, 0.13 mmol), 2- (1,4- diazepan-1-yl) - N - (2,4 45 mg (77%) of the title compound were obtained using -dimethylphenyl) acetamide (47 mg, 0.18 mmol) and NaBH (OAc) ₃ (88 mg, 0.41 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.23 (bs, 1H), 7.94 (d, 1H, J = 8.12 Hz), 7.88 (t, 1H, J = 4.14 Hz), 7.21-7.16 (m, 1H) , 7.02 (t, 1H, J = 7.60 Hz) 4.08 (s, 2H), 3.34 (s, 2H), 2.97-2.92 (m, 8H), 2.28 (d, 6H, J = 8.62 Hz), 1.97-1.91 (m, 2 H).

Example 22. N - (3,4- dimethylphenyl) -2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound No. 22)

6-fluoro in the same manner as in Synthesis Example 3 represents benzothiazol-2-carbazole aldehyde (25 mg, 0.13 mmol), 2- (1,4- diazepan-1-yl) - N - (3,4 43 mg (71%) of the title compound was obtained using -dimethylphenyl) acetamide (47 mg, 0.18 mmol) and NaBH (OAc) ₃ (88 mg, 0.41 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.14 (bs, 1H), 7.88 (t, 1H, J = 4.13 Hz), 7.53 (dd, 1H, J = 8.14, 2.49 Hz), 7.36-7.07 (m, 4H), 4.10 (s, 2H), 3.30 (s, 2H), 2.96-2.90 (m, 8H), 2.24 (d, 6H, J = 11.74 Hz), 1.92-1.85 (m, 2H).

¹³ C NMR (CDCl ₃ , 100 MHz) δ 173.4, 161.5, 159.1, 150.0, 137.3, 136.4, 135.4, 132.5, 130.1, 123.7, 120.7, 116.9, 114.6, 108.1, 62.2, 60.7, 56.6, 56.2, 55.0, 28.4 , 19.9, 19.2.

Example 23. N- (2,6-dimethylphenyl) -2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound No. 23)

6-fluoro in the same manner as in Synthesis Example 3 represents benzothiazol-2-carbazole aldehyde (25 mg, 0.13 mmol), 2- (1,4- diazepan-1-yl) - N - (2,6 29 mg (50%) of the title compound was obtained using -dimethylphenyl) acetamide (47 mg, 0.18 mmol) and NaBH (OAc) ₃ (88 mg, 0.41 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.79 (bs, 1H), 7.88 (t, 1H, J = 4.13 Hz), 7.49 (dd, 1H, J = 8.13, 2.48 Hz), 7.21-7.06 (m, 4H), 4.04 (s, 2H), 3.39 (s, 2H), 3.02-2.92 (m, 8H), 2.23 (s, 6H), 1.97-1.92 (m, 2H).

Example 24. 2-acetamide (2-fluorophenyl) ((4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N Compound number 24)

Benzothiazol-2-carbazole aldehyde (50 mg, 0.42 mmol) 6-fluoro in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (2-fluoro Lophenyl) acetamide (138 mg, 0.55 mmol) and NaBH (OAc) ₃ (270 mg, 1.27 mmol) were used to obtain 83 mg (47%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.67 (bs, 1H), 8.40 (t, 1H, J = 7.96 Hz), 7.88 (q, 1H, J = 4.12 Hz), 7.54 (dd, 1H, J = 8.18, 2.55 Hz), 7.21-7.04 (m, 4H), 4.09 (s, 2H), 3.34 (s, 2H), 2.97-2.90 (m, 8H), 2.97-2.90 (m, 2H).

Example 25. 2-acetamide (3-fluorophenyl) ((4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N Compound number 25)

Benzothiazol-2-carbazole aldehyde (50 mg, 0.42 mmol) 6-fluoro in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (3- fluoro Rophenyl) acetamide (138 mg, 0.55 mmol) and NaBH (OAc) ₃ (270 mg, 1.27 mmol) gave 72 mg (41%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.36 (bs, 1H), 7.89 (q, 1H, J = 4.13 Hz), 7.58-7.53 (m, 2H), 7.26-7.16 (m, 3H), 6.82- 6.80 (m, 1H), 4.10 (s, 2H), 3.31 (s, 2H), 2.96-2.90 (m, 8H), 1.95-1.89 (m, 2H).

Example 26. 2-acetamide (4-fluorophenyl) ((4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N Compound no.26)

Benzothiazol-2-carbazole aldehyde (50 mg, 0.42 mmol) 6-fluoro in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (4- fluoro Rophenyl) acetamide (157 mg, 0.60 mmol) and NaBH (OAc) ₃ (270 mg, 1.27 mmol) gave 79 mg (45%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.26 (bs, 1H), 7.89 (q, 1H, J = 4.78 Hz), 7.58-7.52 (m, 3H,) 7.21-7.16 (m, 1H), 7.05- 6.99 (m, 2H), 4.10 (s, 2H), 3.32 (s, 2H), 3.01-2.83 (m, 8H), 1.96-1.90 (m, 2H).

Example 27. N - (2- chloro-phenyl) -2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound Number 27)

6-fluorobenzothiazole-2-carbaaldehyde (50 mg, 0.42 mmol), N- (2-chlorophenyl) -2- (1,4-diazepane-1- in the same manner as in Synthesis Example 3 I) 73 mg (40%) of the title compound was obtained using acetamide (150 mg, 0.55 mmol) and NaBH (OAc) ₃ (269 mg, 1.27 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 10.01 (bs, 1H), 8.48 (dd, 1H, J = 8.26, 4.13 Hz), 7.87 (q, 1H, J = 4.76 Hz) 7.53 (dd, 1H, J = 8.03, 2.54 Hz), 7.38-7.00 (m, 4H), 4.08 (s, 2H), 3.31 (s, 2H), 2.97-2.89 (m, 8H), 1.98-1.94 (m, 2H).

Example 28. N- (3-Chlorophenyl) -2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (compound Number 28)

6-fluorobenzothiazole-2-carbaaldehyde (50 mg, 0.42 mmol), N- (3-chlorophenyl) -2- (1,4-diazepane-1- in the same manner as in Synthesis Example 3 Il) Acetamide (150 mg, 0.55 mmol) and NaBH (OAc) ₃ (269 mg, 1.27 mmol) were used to obtain 83 mg (45%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.34 (bs, 1H), 7.88 (q, 1H, J = 4.76 Hz), 7.68 (d, 1H, J = 1.64 Hz), 7.54 (dd, 1H, J = 8.10, 2.42 Hz), 7.47-7.44 (m, 1H), 7.26-7.06 (m, 3H), 4.10 (s, 2H), 3.31 (s, 2H), 2.95-2.82 (m, 8H), 1.95-1.89 (m, 2 H).

Example 29. N- (4-Chlorophenyl) -2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (compound Number 29)

6-fluorobenzothiazole-2-carbaaldehyde (50 mg, 0.42 mmol), N- (4-chlorophenyl) -2- (1,4-diazepane-1- in the same manner as in Synthesis Example 3 I) 91 mg (50%) of the title compound were obtained using acetamide (150 mg, 0.55 mmol) and NaBH (OAc) ₃ (269 mg, 1.27 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.41 (bs, 1H), 7.87 (q, 1H, J = 4.78 Hz) 7.68 (d, 1H, J = 1.64 Hz), 7.54-7.51 (m, 3H), 7.33-7.15 (m, 3H), 4.09 (s, 2H), 3.30 (s, 2H), 2.94-2.90 (m, 8H), 1.94-1.86 (m, 2H).

Example 30. 2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide (Compound No. 30 )

6-fluorobenzothiazole-2-carbaaldehyde (50 mg, 0.42 mmol), 2- (1,4-diazepane-1-yl) -N - o -tolylacetic acid in the same manner as in Synthesis Example 3 Amide (136 mg, 0.55 mmol), NaBH (OAc) ₃ (269 mg, 1.27 mmol) was used to give 68 mg (42%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.34 (bs, 1H), 8.12 (d, 1H, J = 8.05 Hz), 7.88 (q, 1H, J = 4.78 Hz) 7.53 (dd, 1H, J = 8.14 , 2.54 Hz), 7.27-7.09 (m, 3H), 7.04 (t, 1H, J = 7.44 Hz), 4.08 (s, 2H), 3.34 (s, 2H), 2.97-2.85 (m, 8H), 2.31 (s, 3 H), 1.96-1.91 (m, 2 H).

Example 31. 2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide (Compound No. 31 )

6-fluorobenzothiazole-2-carbaaldehyde (50 mg, 0.42 mmol), 2- (1,4-diazepane-1-yl) -N - m -tolylacetic acid in the same manner as in Synthesis Example 3 Amide (136 mg, 0.55 mmol), NaBH (OAc) ₃ (269 mg, 1.27 mmol) was used to give 81 mg (51%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.22 (bs, 1H), 7.88 (q, 1H, J = 4.78 Hz), 7.53 (dd, 1H, J = 8.12, 2.50 Hz), 7.43 (s, 1H) 7.38 (d, 1H, J = 8.06 Hz) 7,23-7.15 (m, 2H), 6.92 (d, 1H, J = 7.44 Hz), 4.10 (s, 2H), 3.30 (s, 2H), 2.96- 2.89 (m, 8H), 2.35 (s, 3H), 1.95-1.89 (m, 2H).

Example 32. 2- (4-((6-fluorobenzothiazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide (Compound No. 32 )

6-fluorobenzothiazole-2-carbaaldehyde (50 mg, 0.42 mmol), 2- (1,4-diazepan-1-yl) -N - p -tolylacetic acid in the same manner as in Synthesis Example 3 Amide (136 mg, 0.55 mmol), NaBH (OAc) ₃ (269 mg, 1.27 mmol) was used to give 67 mg (42%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.20 (bs, 1H), 7.89 (q, 1H, J = 4.78 Hz), 7.54 (dd, 1H, J = 8.14, 2.52 Hz), 7.47 (d, 1H, J = 8.24 Hz), 7,22-7.13 (m, 3H), 4.10 (s, 2H), 3.31 (s, 2H), 2.96-2.91 (m, 8H), 2.32 (s, 3H) 1.96-1.90 ( m, 2H).

Example 33 2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-methoxyphenyl) acetamido-Id (Compound No. 33)

Benzothiazol-2-carbazole aldehyde (50 mg, 0.42 mmol) 6-fluoro in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (2-methoxy 92 mg (55%) of the title compound was obtained using oxyphenyl) acetamide (145 mg, 0.55 mmol) and NaBH (OAc) ₃ (269 mg, 1.27 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.86 (bs, 1H), 8.42 (d, 1H, J = 7.86 Hz), 7.88 (q, 1H, J = 4.79 Hz), 7.54 (dd, 1H, J = 8.13, 1.44 Hz), 7,20-6.88 (m, 4H), 4.10 (s, 2H), 3.91 (s, 3H), 3.31 (s, 2H), 3.00-2.86 (m, 8H), 1.98-1.92 (m, 2 H).

Example 34 2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamido Id (Compound No. 34)

Benzothiazol-2-carbazole aldehyde (50 mg, 0.42 mmol) 6-fluoro in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (3- methoxy 95 mg (56%) of the title compound was obtained using oxyphenyl) acetamide (145 mg, 0.55 mmol) and NaBH (OAc) ₃ (269 mg, 1.27 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.27 (bs, 1H), 7.89 (q, 1H, J = 4.77 Hz), 7.54 (dd, 1H, J = 8.12, 2.07 Hz), 7.38 (t, 1H, J = 2.07 Hz), 7,25-7.18 (m, 2H), 7,06-7.04 (m, 1H), 6.68-6.66 (m, 1H), 4.10 (s, 2H), 3.81 (s, 3H) , 3.31 (s, 2H), 3.00-2.83 (m, 8H), 1.96-1.90 (m, 2H).

Example 35 2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- methoxyphenyl) acetamido Id (Compound No. 35)

Benzothiazol-2-carbazole aldehyde (50 mg, 0.42 mmol) 6-fluoro in the same manner as in the representative synthesis example 3, 2- (1,4-diazepan-1-yl) - N - (4- methoxy 75 mg (45%) of the title compound was obtained using oxyphenyl) acetamide (145 mg, 0.55 mmol) and NaBH (OAc) ₃ (269 mg, 1.27 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.15 (bs, 1H), 7.89 (q, 1H, J = 4.77 Hz), 7,55-7.46 (m, 3H), 7,21-7.16 (m, 1H ), 6.88 (dd, 1H, J = 8.77, 3.20 Hz), 4.10 (s, 2H), 3.80 (s, 3H), 3.31 (s, 2H), 2.96-2.82 (m, 8H), 1.97-1.90 ( m, 2H).

Example 36 2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl Acetamide (Compound No. 36)

6-fluoro in the same manner as in Synthesis Example 3 represents benzothiazol-2-carbazole aldehyde (50 mg, 0.42 mmol), 2- (1,4- diazepan-1-yl) - N - (2- ( Trifluoromethyl) phenyl) acetamide (166 mg, 0.55 mmol) and NaBH (OAc) ₃ (269 mg, 1.27 mmol) were used to give 52 mg (28%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.98 (bs, 1H), 8.44 (d, 1H, J = 8.30 Hz) 7.88 (q, 1H, J = 4.79 Hz), 7,62-7.52 (m, 3H ), 7,20-7.15 (m, 2H), 4.08 (s, 2H), 3.34 (s, 2H), 2.96-2.92 (m, 8H), 1.97-1.91 (m, 2H).

Example 37 2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl Acetamide (Compound No. 37)

6-fluoro in the same manner as in Synthesis Example 3 represents benzothiazol-2-carbazole aldehyde (50 mg, 0.42 mmol), 2- (1,4- diazepan-1-yl) - N - (3- ( Trifluoromethyl) phenyl) acetamide (166 mg, 0.55 mmol) and NaBH (OAc) ₃ (269 mg, 1.27 mmol) were used to obtain 107 mg (58%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.46 (bs, 1H), 7,91-7.82 (m, 3H), 7.54 (dd, 1H, J = 5.58, 2.54 Hz) 7.45 (t, 1H, J = 7.92 Hz), 7.36 (d 1H, J = 7.77 Hz) 7.16 (ddd, 1H, J = 6.62, 6.62, 2.25 Hz), 4.11 (s, 2H), 3.35 (s, 2H), 2.98-2.88 (m, 8H), 1.97-1.91 (m, 2H).

Example 38 2- (4 - ((6-fluoro-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl Acetamide (Compound No. 38)

6-fluoro in the same manner as in Synthesis Example 3 represents benzothiazol-2-carbazole aldehyde (50 mg, 0.42 mmol), 2- (1,4- diazepan-1-yl) - N - (4- ( Trifluoromethyl) phenyl) acetamide (166 mg, 0.55 mmol) and NaBH (OAc) ₃ (269 mg, 1.27 mmol) were used to give 86 mg (90%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.48 (bs, 1H), 7,88 (q, 2H, J = 4.79 Hz), 7,70 (d, 2H, J = 8.50 Hz), 7,56 ( d, 1H, J = 8.62 Hz), 7.53 (dd, 1H, J = 5.58, 2.54 Hz). 7.18 (ddd, 1H, J = 6.35, 6.35, 2.55 Hz), 4.10 (s, 2H), 3.33 (s, 2H), 2.95-2.91 (m, 8H), 1.95-1.89 (m, 2H).

Example 39. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (2,6- diethyl-phenyl Acetamide (Compound No. 39)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (60 mg, 0.36 mmol) and 2- (1,4-diazepan-1-yl) - N - (2, 88 mg (58%) of the title compound were obtained using 6-diethylphenyl) acetamide (135 mg, 0.47 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.81 (bs, 1H), 7.70 (bs, 2H), 7.25-7.12 (m, 5H), 3.95 (s, 2H), 3.36 (s, 2H), 2.96- 2.82 (m, 8H), 2.59 (q, 4H, J = 7.50 Hz), 1.93-1.86 (m, 2H), 1.17 (t, 6H, J = 6.37 Hz).

Example 40. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2,4- dimethylphenyl) Acetamide (Compound No. 40)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (60 mg, 0.36 mmol) and 2- (1,4-diazepan-1-yl) - N - (2, 114 mg (81%) of the title compound was obtained using 4-dimethylphenyl) acetamide (122 mg, 0.47 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.15 (bs, 1H), 7.82 (d, 1H, J = 7.88 Hz), 7.55 (t, 2H, J = 2.90 Hz), 7.22-7.20 (m, 2H) , 6.98 (d, 2H, J = 8.64 Hz), 3.94 (s, 2H), 3.25 (s, 2H), 2.95-2.85 (m, 8H), 2.22 (dd, 6H, J = 13.62, 7.69 Hz), 1.84-1.80 (m, 2 H),

Example 41. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3,4- dimethylphenyl) Acetamide (Compound No. 41)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (50 mg, 0.30 mmol) and 2- (1,4-diazepan-1-yl) - N - (3, 50 mg (43%) of the title compound were obtained using 4-dimethylphenyl) acetamide (102 mg, 0.39 mmol) and EDIPA (110 μL, 0.60 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.08 (bs, 1H), 7.58 (bs, 1H), 7.34 (d, 1H, J = 1.75 Hz), 7.30-7.22 (m, 3H), 7.07 (d, 1H, J = 8.10 Hz), 3.98 (s, 2H), 3.26 (s, 2H), 2.88-2.77 (m, 8H), 2.23 (d, 6H, J = 8.85 Hz), 1.89-1.83 (m, 2H ).

Example 42. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2,6- dimethylphenyl) Acetamide (Compound No. 42)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (50 mg, 0.30 mmol) and 2- (1,4-diazepan-1-yl) - N - (2, 80 mg (68%) of the title compound were obtained using 6-dimethylphenyl) acetamide (102 mg, 0..39 mmol) and EDIPA (110 μL, 0.60 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.76 (bs, 1H), 7.54 (bs, 1H), 7.24-7.20 (m, 2H), 7.13-7.06 (m, 3H), 3.93 (s, 2H), 3.34 (s, 2H), 2.96-2.76 (m, 8H), 2.21 (s, 2H), 1.90-1.84 (m, 2H).

Example 43. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-fluorophenyl) acetamide Amide (Compound No. 43)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (50 mg, 0.30 mmol) and 2- (1,4-diazepan-1-yl) - N - (2- 59 mg (52%) of the title compound were obtained using fluorophenyl) acetamide (98 mg, 0.39 mmol) and EDIPA (110 μL, 0.60 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.68 (bs, 1H), 8.42-8.38 (m, 1H), 7.59 (bs, 1H), 8.27-7.03 (m, 5H) 3.93 (s, 2H), 3.32 (s, 2H), 2.94-2.86 (m, 8H), 1.92-1.87 (m, 2H).

Example 44. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3-fluorophenyl) acetamide Amide (Compound No. 44)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (50 mg, 0.30 mmol) and 2- (1,4-diazepan-1-yl) - N - (3- Fluorophenyl) acetamide (98 mg, 0.39 mmol) and EDIPA (110 μL, 0.60 mmol) were used to give 30 mg 26%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.95 (bs, 1H), 9.28 (s, 1H), 7.58-7.55 (m, 2H), 7.26-7.17 (m, 4H), 6.82-6.81 (m, 1H), 3.99 (s, 2H), 3.28 (s, 2H), 2.90-2.85 (m, 8H), 1.95-1.19 (m, 2H),

Example 45. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4-fluorophenyl) acetamide Amide (Compound No. 45)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (50 mg, 0.30 mmol) and 2- (1,4-diazepan-1-yl) - N - (4- 49 mg (42%) of the title compound were obtained using fluorophenyl) acetamide (98 mg, 0.39 mmol) and EDIPA (110 μL, 0.60 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 921 (bs, 1H), 7.58-6.99 (m, 8H), 3.99 (s, 2H), 3.28 (s, 2H), 2.89-2.84 (m, 8H), 1.91-1.85 (m, 2 H).

Example 46. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- chlorophenyl) acetamide (Compound No. 46)

2- (chloromethyl) -1 H -benzoimidazole (60 mg, 0.36 mmol) and N- (2-chlorophenyl) -2- (1,4-diazepane-1 in the same manner as in Synthesis Example 4 -Yl) acetamide (125 mg, 0.46 mmol) and EDIPA (130 μL, 0.72 mmol) were used to obtain 83 mg (83%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.92 (bs, 1H), 8.45 (d, 1H, J = 8.24 Hz), 7.56 (t, 2H, J = 3.94 Hz), 7.36 (d, 1H, J = 8.04 Hz), 7.30-6.91 (m, 4H), 3.98 (s, 2H), 3.28 (s, 2H), 2.88-2.83 (m, 8H), 1.92-1.87 (m, 2H).

Example 47. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- chlorophenyl) acetamide (Compound No. 47)

2- (chloromethyl) -1 H -benzoimidazole (60 mg, 0.36 mmol) and N- (3-chlorophenyl) -2- (1,4-diazepane-1 in the same manner as in Synthesis Example 4 above 76 mg (53%) of the title compound were obtained using -yl) acetamide (125 mg, 0.46 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.33 (bs, 1H), 7.72-7.00 (m, 8H), 4.04 (s, 2H), 3.27 (s, 2H), 2.90-2.83 (m, 8H), 1.89-1.87 (m, 2 H).

Example 48. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- chlorophenyl) acetamide (Compound No. 48)

2- (chloromethyl) -1 H -benzoimidazole (60 mg, 0.36 mmol) and N- (4-chlorophenyl) -2- (1,4-diazepane-1 in the same manner as in Synthesis Example 4 above 108 mg (75%) of the title compound were obtained using -yl) acetamide (125 mg, 0.46 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.26 (bs, 1H), 7.57-7.50 (m, 4H), 7.26-7.22 (m, 4H), 3.99 (s, 2H), 3.25 (s, 2H), 2.86-2.82 (m, 8 H), 1.86-1.84 (m, 2 H).

Example 49. 2- (4-(( 1H -Benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - o -tolylacetamide (Compound No. 49)

2- (chloromethyl) -1 H -benzoimidazole (60 mg, 0.36 mmol) and 2- (1,4-diazepan-1-yl) -N - o -tolyl in the same manner as in Synthesis Example 4 111 mg (82%) of the title compound were obtained using acetamide (116 mg, 0.47 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.25 (bs, 1H), 8.05 (d, 1H, J = 7.98 Hz), 7.55 (s, 2H), 7.25-7.02 (m, 5H), 3.95 (s, 2H), 3.27 (s, 2H), 2.90-2.82 (m, 8H), 2.21 (s, 3H), 1.88-1.84 (m, 2H).

Example 50. 2- (4-(( 1H -Benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide (Compound No. 50)

2- (chloromethyl) -1 H -benzoimidazole (60 mg, 0.36 mmol) and 2- (1,4-diazepan-1-yl) -N - m -tolyl in the same manner as in Synthesis Example 4 59 mg (44%) of the title compound was obtained using acetamide (116 mg, 0.47 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.17 (bs, 1H), 7.57 (q, 2H, J = 2.84 Hz), 7.41 (s, 1H), 7.34 (d, 1H, J = 7.85 Hz), 7.24 -7.17 (m, 3H), 6.92 (d, 1H, J = 7.40 Hz) 3.99 (s, 2H), 3.25 (s, 2H), 2.88-2.80 (m, 8H), 2.33 (s, 3H), 1.90 -1.84 (m, 2 H).

Example 51. 2- (4-(( 1H -Benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide (Compound No. 51)

2- (chloromethyl) -1 H -benzoimidazole (60 mg, 0.36 mmol) and 2- (1,4-diazepane-1-yl) -N - p -tolyl in the same manner as in Synthesis Example 4 Acetamide (116 mg, 0.47 mmol) and EDIPA (130 μL, 0.72 mmol) were used to yield 98 mg (72%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.15 (bs, 1H), 7.57 (bs, 2H), 7.43 (d, 2H, J = 8.26 Hz), 7.25-7.21 (m, 2H), 7.10 (d, 2H, J = 8.4 Hz), 3.98 (s, 2H), 3.24 (s, 2H), 2.84-2.81 (m, 8H), 2.3 (s, 3H), 1.87-1.81 (m, 2H).

Example 52. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- methoxyphenyl) acetamide Amide (Compound No. 52)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (60 mg, 0.36 mmol) and 2- (1,4-diazepan-1-yl) - N - (2- 107 mg (75%) of the title compound were obtained using methoxyphenyl) acetamide (123 mg, 0.47 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.84 (bs, 1H), 8.41 (d, 2H, J = 7.92 Hz), 7.55 (s, 2H), 7.26-7.21 (m, 2H), 7.04 (t, 1H, J = 7.94 Hz), 6.96 (t, 1H, J = 7.78 Hz), 6.89 (d, 1H, J = 8.10 Hz) 4.00 (s, 2H), 3.88 (s, 3H), 3.29 (s, 2H ), 2.91-2.81 (m, 8H), 1.93-1.87 (m, 2H),

Example 53. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide Amide (Compound No. 53)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (60 mg, 0.36 mmol) and 2- (1,4-diazepan-1-yl) - N - (3- 63 mg (44%) of the title compound were obtained using methoxyphenyl) acetamide (123 mg, 0.47 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.22 (bs, 1H), 7.57 (s, 2H), 7.37 (d, 2H, J = 1.96 Hz), 7.25-7.20 (m, 3H), 7.01 (d, 1H, J = 7.94 Hz), 6.67 (dd, 1H, J = 6.05, 2.14 Hz), 4.01 (s, 2H), 3.80 (s, 3H), 3.28 (s, 2H), 2.90-2.84 (m, 8H ), 1.90-1.87 (m, 2H),

Example 54. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- methoxyphenyl) acetamide Amide (Compound No. 54)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (60 mg, 0.36 mmol) and 2- (1,4-diazepan-1-yl) - N - (4- 54 mg (38%) of the title compound were obtained using methoxyphenyl) acetamide (123 mg, 0.47 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.12 (bs, 1H), 7.57 (t, 2H, J = 2.74 Hz), 7.47-7.44 (m, 2H), 7.26-7.22 (m, 2H), 6.84 ( dd, 2H, J = 4.68, 2.20 Hz), 3.99 (s, 2H), 3.77 (s, 3H), 3.25 (s, 2H), 2.89-2.77 (m, 8H), 1.86-1.82 (m, 2H) .

Example 55. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl ) Phenyl) acetamide (Compound No. 55)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (60 mg, 0.36 mmol) and 2- (1,4-diazepan-1-yl) - N - (2- 103 mg (66%) of the title compound were obtained using (trifluoromethyl) phenyl) acetamide (141 mg, 0.41 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.23 (bs, 1H), 8.42 (d, 1H, J = 8.30 Hz), 7.62-7.18 (m, 7H), 3.97 (s, 2H), 3.30 (s, 2H), 2.90-2.83 (m, 8H), 1.91-1.86 (m, 2H).

Example 56. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl ) Phenyl) acetamide (Compound No. 56)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (60 mg, 0.36 mmol) and 2- (1,4-diazepan-1-yl) - N - (3- 85 mg (55%) of the title compound were obtained using (trifluoromethyl) phenyl) acetamide (141 mg, 0.41 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.45 (bs, 1H), 7.92 (s, 1H), 7.74 (d, 1H, J = 7.95 Hz), 7.59-7.21 (m, 6H), 4.01 (s, 2H), 3.27 (s, 2H), 2.89-2.82 (m, 8H), 1.86-1.82 (m, 2H).

Example 57. 2- (4 - ((1 H - benzo [d] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl ) Phenyl) acetamide (Compound No. 57)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -1 H - benzoimidazole (60 mg, 0.36 mmol) and 2- (1,4-diazepan-1-yl) - N - (4- 91 mg (58%) of the title compound were obtained using (trifluoromethyl) phenyl) acetamide (141 mg, 0.41 mmol) and EDIPA (130 μL, 0.72 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.44 (bs, 1H), 7.67 (d, 2H, J = 8.50 Hz), 7.54 (q, 4H, J = 2.69 Hz), 7.24-7.21 (m, 2H) , 3.97 (s, 2H), 3.25 (s, 2H), 2.83-2.79 (m, 8H), 1.86-1.82 (m, 2H).

Example 58. N- (2,6-diethylphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl Acetamide (Compound No. 58)

A target compound having a yield of 83% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.77 (bs, 1H), 7.63 (d, 2H, J = 8.2 Hz), 7.42 (t, 2H, J = 1.6 Hz), 7.39-7.19 (m, 2H) , 7.12 (d, 2H, J = 7.6 Hz), 3.87 (s, 2H), 3.34 (s, 2H), 2.9 (m, 8H), 2.83 (t, 2H, J = 7.6 Hz), 2.57 (q, 4H, J = 7.6 Hz), 1.9 (quintet, 2H, J = 6 Hz), 1.73 (q, 2H, J = 7.2 Hz), 1.18 (t, 6H, J = 7.6 Hz), 0.97 (t, 3H, J = 7.2 Hz).

Example 59. N - (2,3- dimethylphenyl) -2- (4 - ((4-phenyl-5-propyl-oxazol-2-yl) methyl) -1,4-diazepan-1-yl) Acetamide (Compound No. 59)

A target compound having a yield of 73% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.23 (bs, 1H), 7.93 (d, 1H , J = 8.0 Hz), 7.63 (d, 2H , J = 8 Hz), 7.41 (t, 2H, J = 8 Hz), 7.32 (m, 1H), 7.02 (d, 1H, J = 8.2 Hz), 6.97 (s, 1H), 3.87 (s, 2H), 3.29 (s, 2H), 2.93-2.83 (m, 10H), 2.28 (s, 3H), 2.22 (s, 3H), 1.9 (m, 2H), 1.75 (q, 2H, J = 7.6 Hz), 0.99 (t, 3H, J = 7.6 Hz).

Example 60. N- (3,4-Dimethylphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) Acetamide (Compound No. 60)

A target compound having a yield of 72% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.13 (bs, 1H), 7.64 (d, 2H , J = 8.0 Hz), 7.41 (t, 2H, J = 7.8 Hz), 7.36 (s, 1H), 7.32 -7.27 (m, 1H), 7.03 (d, 1H, J = 8 Hz), 3.89 (s, 2H), 3.25 (s, 2H), 2.93-2.84 (m, 10H), 2.23 (s, 3H), 2.21 (s, 3H), 1.87 (quintet, 2H, J = 5.6 Hz), 1.76 (q, 2H, J = 7.6 Hz), 1.0 (t, 3H, J = 7.6 Hz).

Example 61. N- (2,4-Dimethylphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) Acetamide (Compound No. 61)

A target compound having a yield of 68% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.76 (bs, 1H), 7.62 (d, 2H, J = 7.4 Hz), 7.40 (t, 2H, J = 8 Hz), 7.31 (d, 1H, J = 7.2 Hz), 7.09 (m, 3H), 3.87 (s, 2H), 3.34 (s, 2H), 2.96-2.89 (m, 8H), 2.83 (t, 3H, J = 7.6 Hz), 2.2 (s, 6H), 1.91 (quintet, 2H, J = 6 Hz), 1.74 (q, 2H, J = 7.4 Hz), 0.98 (t, 3H, J = 7.4 Hz).

Example 62. N- (2-Chlorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound No. 62)

A target compound having a yield of 76% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.99 (bs, 1H), 8.48 (d, 1H , J = 8 Hz), 7.64 (d, 2H, J = 8 Hz), 7.41 (t, 2H, J = 7.6 Hz), 7.35-7.26 (m, 3H), 7.01 (t, 1H, J = 7.2 Hz), 3.88 (s, 2H), 3.3 (s, 2H), 2.97-2.83 (m, 10H), 1.94 ( quintet, 2H, J = 6 Hz), 1.75 (q, 2H, J = 7.4 Hz), 0.99 (t, 3H, J = 7.6 Hz).

Example 63. N- (3-Chlorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound No. 63)

A target compound having a yield of 55% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.79 (bs, 1H), 7.71 (s, 1H), 7.63 (d, 2H, J = 7.6 Hz), 7.41 (t, 3H, J = 7.6 Hz), 7.38 (m, 3H), 7.18 (t, 1H, J = 8 Hz), 7.07 (d, 1H, J = 6 Hz), 3.9 (s, 2H), 3.27 (s, 2H), 2.95-2.83 (m, 10H), 1.91 (quintet, 2H, J = 4 Hz), 1.75 (q, 2H, J = 7.4 Hz), 0.99 (t, 3H, J = 7.4 Hz).

Example 64. N- (4-Chlorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound No. 64)

A target compound having a yield of 46% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.37 (bs, 1H), 7.64 (d, 2H , J = 8 Hz), 7.53 (d, 2H, J = 8.8 Hz), 7.42 (t, 2H, J = 7.6 Hz), 7.33 (d, 1H, J = 7.6 Hz), 7.2 (d, 2H, J = 6.8 Hz), 3.9 (s, 2H), 3.27 (s, 2H), 2.94-2.83 (m, 10H) , 1.91 (quintet, 2H, J = 5.6 Hz), 1.76 (q, 2H, J = 7.4 Hz), 0.99 (t, 3H, J = 7.4 Hz).

Example 65. N- (2-fluorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acet Amide (Compound No. 65)

A target compound having a yield of 80% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.65 (bs, 1H), 8.89 (t, 1H , J = 7.6 Hz), 7.64 (d, 2H, J = 8.4 Hz), 7.4 (t, 2H, J = 7.6 Hz), 7.3 (d, 1H, J = 7.2 Hz), 7.11-7.01 (m, 3H), 3.88 (s, 2H), 3.3 (s, 2H), 2.95-2.83 (m, 10H), 1.92 ( quintet, 2H, J = 5.8 Hz), 1.76 (q, 2H, J = 7.4 Hz), 0.99 (t, 3H, J = 7.4 Hz).

Example 66. N- (3-fluorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl (compound Number 66)

A target compound having a yield of 65% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.39 (bs, 1H), 7.64 (d, 2H, J = 7.2 Hz), 7.54 (d, 1H, J = 8.4 Hz), 7.41 (t, 2H, J = 7.6 Hz), 7.3-7.17 (m, 3H), 6.77 (d, 1H, J = 6 Hz), 3.89 (s, 2H), 3.27 (s, 2H), 2.94-2.83 (m, 10H), 1.91 ( quintet, 2H, J = 6 Hz), 1.75 (q, 2H, J = 7.6 Hz), 0.99 (t, 3H, J = 7.4 Hz).

Example 67 N- (4-fluorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acet Amide (Compound No. 67)

A target compound having a yield of 52% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.3 (bs, 1H), 7.65 (d, 2H , J = 8.4 Hz), 7.53 (q, 2H, J = 4.4 Hz), 7.42 (t, 2H, J = 7 Hz), 7.32 (d, 1H, J = 7.6 Hz), 6.96 (t, 2H, J = 8.8 Hz), 3.9 (s, 2H), 3.27 (s, 2H), 2.94-2.83 (m, 10H) , 1.90 (quintet, 2H, J = 4 Hz), 1.75 (q, 2H, J = 7.6 Hz), 0.99 (t, 3H, J = 7.4 Hz).

Example 68. 2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide (Compound No. 68)

A target compound having a yield of 57% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.36 (bs, 1H), 8.13 (d, 1H , J = 7.8 Hz), 7.65 (d, 2H, J = 7.2 Hz), 7.42 (t, 2H, J = 7.5 Hz), 7.34-7.15 (m, 3H), 7.04 (d, 1H, J = 7.5 Hz), 3.88 (s, 2H), 3.32 (s, 2H), 2.96-2.83 (m, 10H), 1.94 ( quintet, 2H, J = 5.7 Hz), 1.77 (q, 2H, J = 7.5 Hz), 1.0 (t, 3H, J = 7.5 Hz).

Example 69. 2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide (Compound No. 69)

A target compound having a yield of 57% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.25 (bs, 1H), 7.66 (d, 2H, J = 7.5 Hz), 7.45 (t, 3H, J = 7.5 Hz), 7.36-7.27 (m, 2H) , 7.18 (t, 1H, J = 7.5 Hz), 6.92 (d, 1H, J = 7.5 Hz), 3.9 (s, 2H), 3.28 (s, 2H), 2.94-2.84 (m, 10H), 2.34 ( s, 3H), 1.94 (quintet, 2H, J = 6 Hz), 1.78 (q, 2H, J = 7.5 Hz), 1.0 (t, 3H, J = 7.5 Hz).

Example 70. 2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p- tolylacetamide (Compound No. 70)

The title compound was obtained in the same manner as the representative synthesis example, with a yield of 62%.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.23 (bs, 1H), 7.65 (d, 2H , J = 7.5 Hz), 7.46-7.27 (m, 5H), 7.1 (d, 2H, J = 8.4 Hz) , 3.9 (s, 2H), 3.26 (s, 2H), 2.95-2.84 (m, 10H), 1.94 (quintet, 2H, J = 6 Hz), 1.78 (q, 2H, J = 7.5 Hz), 1.0 ( t, 3H, J = 7.5 Hz).

Example 71. N - (2- methoxy-phenyl) -2- (4 - ((4-phenyl-5-propyl-oxazol-2-yl) methyl) -1,4-diazepan-1-yl) ( Compound number 71)

A target compound having a yield of 51% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.82 (bs, 1H), 8.4 (d, 1H , J = 8 Hz), 7.64 (d, 2H, J = 7.2 Hz), 7.41 (t, 2H, J = 7.6 Hz), 7.30 (m, 1H), 7.04-6.96 (m, 2H), 6.87 (d, 1H, J = 8 Hz), 3.89 (s, 2H), 3.85 (s, 3H), 3.28 (s, 2H), 2.98-2.83 (m, 10H), 1.93 (quintet, 2H, J = 6 Hz), 1.76 (q, 2H, J = 7.4 Hz), 0.99 (t, 3H, J = 7.4 Hz).

Example 72. N- (3-methoxyphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acet Amide (Compound No. 72)

A target compound having a yield of 53% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.29 (bs, 1H), 7.64 (d, 2H, J = 8 Hz), 7.41 (m, 3H), 7.31 (d, 1H, J = 7.6 Hz), 7.16 (t, 1H, J = 8 Hz), 7.01 (d, 1H, J = 1.2 Hz), 6.6 (d, 1H, J = 2 Hz), 3.89 (s, 2H), 3.80 (s, 3H), 3.26 (s, 3H), 2.94-2.83 (m, 10H), 1.91 (quintet, 2H, J = 5.6 Hz), 1.76 (q, 2H, J = 7.4 Hz), 0.99 (t, 3H, J = 7.4 Hz) .

Example 73. N- (4-methoxyphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acet Amide (Compound No. 73)

A target compound having a yield of 47% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.18 (bs, 1H), 7.64 (d, 2H , J = 7.6 Hz), 7.48-7.39 (m, 4H), 7.31 (d, 1H, J = 7.2 Hz) , 6.82 (d, 2H, J = 6.8 Hz), 3.9 (s, 2H), 3.77 (s, 3H), 3.26 (s, 2H), 2.94-2.83 (m, 10H), 1.91 (quintet, 2H, J = 5.6 Hz), 1.76 (q, 2H, J = 7.4 Hz), 0.99 (t, 3H, J = 7.4 Hz).

Example 74. 2- (4 - ((4-phenyl-5-propyl-oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl ) Phenyl) acetamide (Compound No. 74)

A target compound having a yield of 63% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.97 (bs, 1H), 8.43 (d, 1H , J = 7.6 Hz), 7.64-7.54 (m, 4H), 7.40 (t, 2H, J = 8 Hz) , 7.30 (d, 1H, J = 7.2 Hz), 7.18 (m, 1H), 3.87 (s, 2H), 3.27 (s, 2H), 2.94-2.83 (m, 10H), 1.92 (quintet, 2H, J = 5.6 Hz), 1.76 (q, 2H, J = 7.4 Hz), 0.99 (t, 3H, J = 7.4 Hz).

Example 75. 2- (4 - ((4-phenyl-5-propyl-oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl ) Phenyl) acetamide (Compound No. 75)

The title compound was obtained in the same manner as the representative synthesis example above, with a yield of 64%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.5 (bs, 1H), 7.91 (s, 1H), 7.65-7.62 (m, 3H), 7.43-7.31 (m, 5H), 3.9 (s, 2H), 3.31 (s, 2H), 2.93-2.83 (m, 10H), 1.91 (quintet, 2H, J = 6 Hz), 1.76 (q, 2H, J = 7.4 Hz), 0.99 (t, 3H, J = 7.2 Hz ).

Example 76. 2- (4 - ((4-phenyl-5-propyl-oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl ) Phenyl) acetamide (Compound No. 76)

A target compound having a yield of 63% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.5 (bs, 1H), 7.70 (d, 2H , J = 8 Hz), 7.64 (d, 1H, J = 7.8 Hz), 7.50 (d, 2H, J = 6.8 Hz), 7.42 (t, 2H, J = 8 Hz), 7.34 (m, 1H), 3.93 (s, 3H), 3.34 (s, 2H), 2.95-2.83 (m, 10H), 1.92 (quintet, 2H, J = 6 Hz), 1.76 (q, 2H, J = 7.4 Hz), 0.99 (t, 3H, J = 7.2 Hz).

Example 77. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (2,6- diethyl-phenyl) acetamide ( Compound number 77)

Homopiperazine (150 mg, 0.518 mmol) and imidazole derivative (75 mg, 0.77 mmol) were added to MeOH (8 mL) in the same manner as the representative synthesis example, and NaCNBH ₃ (98 mg, 1.55 mmol) was added thereto. It was added and stirred to obtain the target compound (100 mg, 52%).

¹ H NMR (CDCl ₃ , 300 MHz) δ 8.77 (bs, 1H), 7.23-7.19 (m, 1H), 7.13 (d, 2H, J = 7.6 Hz), 6.95 (s, 2H), 3.75 (s, 2H), 3.34 (s, 2H), 2.95-2.88 (m, 4H), 2.78-2.75 (m, 4H), 2.57 (q, 4H, J = 7.6 Hz), 1.88 (quintet, 2H, J = 6 Hz ), 1.17 (t, 6H, J = 7.8 Hz).

Example 78. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (2,4- dimethyl-phenyl) -acetamide (compound Number 78)

A target compound having a yield of 54% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.3 (bs, 1H), 7.9 (d, 1H, J = 8 Hz), 7.0 (m, 4H), 3.78 (s, 2H), 3.28 (s, 2H) , 2.90-2.75 (m, 8H), 2.28 (s, 3H), 2.24 (s, 3H), 1.88 (quintet, 2H, J = 6 Hz).

Example 79. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (3,4- dimethyl-phenyl) -acetamide (compound Number 79)

A target compound having a yield of 28% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.3 (bs, 1H), 7.33 (m, 2H), 7.08 (m, 1H), 7.0 (s, 2H), 3.84 (s, 2H), 3.25 (s, 2H), 2.86-2.81 (m, 8H), 2.25 (s, 3H), 2.20 (s, 3H), 1.87 (quintet, 2H, J = 6 Hz).

Example 80. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (2,6- dimethyl-phenyl) -acetamide (compound Number 80)

The title compound was obtained in the same manner as the representative synthesis example, yield 48%.

¹ H NMR (CDCl ₃ , 300 MHz) δ 8.74 (bs, 1H), 7.10 (m, 3H),, 6.96 (s, 2H), 3.76 (s, 2H), 3.34 (s, 2H), 2.95-2.88 (m, 4H), 2.78-2.76 (m, 4H), 2.21 (s, 6H), 1.87 (quintet, 2H, J = 5.6 Hz).

Example 81. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (2- chlorophenyl) acetamide (Compound No. 81 )

A target compound having a yield of 35% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.97 (bs, 1H), 9.61 (bs, 1H), 8.45 (d, 1H, J = 8.4 Hz), 7.38 (d, 1H, J = 8 Hz), 7.27 (m, 1H), 7.06 (m, 1H), 7.0 (s, 2H), 3.81 (s, 2H), 3.31 (s, 2H), 2.91-2.80 (m, 8H), 1.91 (quintet, 2H, J = 6 Hz).

Example 82. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (3- chlorophenyl) acetamide (Compound No. 82 )

A target compound having a yield of 24% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.27 (bs, 1H), 7.68 (s, 1H), 7.42 (m, 1H), 7.27 (s, 1H), 7.07 (d, 1H, J = 6 Hz) , 7.01 (s, 2H), 3.81 (s, 2H), 3.27 (s, 2H), 2.88-2.75 (m, 8H), 1.86 (quintet, 2H, J = 6 Hz).

Example 83. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (4- chlorophenyl) acetamide (Compound No. 83 )

A target compound having a yield of 46% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.26 (bs, 1H), 7.53 (d, 2H, J = 6.8 Hz), 7.38 (d, 2H, J = 6.8 Hz), 7.0 (s, 2H), 3.80 (s, 2H), 3.25 (s, 2H), 2.86-2.73 (m, 8H), 1.84 (quintet, 2H, J = 6 Hz).

Example 84. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-fluorophenyl) acetamide (Compound No. 84)

A target compound having a yield of 61% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.66 (bs, 1H), 8.39 (m, 1H), 7.14-7.04 (m, 3H), 7.01 (s, 2H), 3.80 (s, 2H), 3.30 ( s, 2H), 2.89-2.78 (m, 8H), 1.87 (quintet, 2H, J = 6 Hz).

Example 85. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3-fluorophenyl) acetamide (Compound No. 85)

A target compound having a yield of 25% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.31 (bs, 1H), 7.68 (s, 1H), 7.55 (d, 1H, J = 6.8 Hz), 7.28-7.19 (m, 2H), 7.01 (s, 2H), 6.08 (m, 1H), 3.86 (s, 2H), 3.27 (s, 2H), 2.87-2.75 (m,

Example 86. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- fluorophenyl) -acetamide (Compound No. 86)

A target compound having a yield of 46% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.2 (bs, 1H), 7.52 (m, 2H), 7.03-6.99 (m, 4H), 3.81 (s, 2H), 3.25 (s, 2H), 2.87- 2.74 (m, 8 H), 1.85 (quintet, 2 H, J = 6 Hz).

Example 87. 2- (4-(( 1H -imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - o -tolylacetamide (Compound No. 87)

A target compound having a yield of 46% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.27 (bs, 1H), 8.08 (d, 1H, J = 8 Hz), 7.22-7.16 (m, 2H), 7.06-7.02 (m, 1H), 6.98 (s , 2H), 3.77 (s, 2H), 3.28 (s, 2H), 2.88-2.75 (m, 8H), 1.86 (quintet, 2H, J = 6 Hz).

Example 88. 2- (4-(( 1H -imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - m -tolylacetamide (Compound No. 88)

A target compound having a yield of 45% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.16 (bs, 1H), 7.38 (s, 1H), 7.35 (d, 1H, J = 8.4 Hz), 7.20 (t, 1H, J = 7.8 Hz), 7.03 (s, 2H), 6.92 (d, 1H, J = 7.2 Hz), 3.75 (s, 2H), 3.23 (s, 2H), 2.85-2.73 (m, 8H), 2.33 (s, 3H), 1.86 ( quintet, 2H, J = 6 Hz).

Example 89. 2- (4-(( 1H -imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - p -tolylacetamide (Compound No. 89)

A target compound having a yield of 43% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.14 (bs, 1H), 7.45 (d, 2H, J = 8 Hz), 7.14 (d, 2H, J = 8 Hz), 7.00 (s, 2H), 3.80 (s, 2H), 3.25 (s, 2H), 2.86-2.74 (m, 8H), 2.31 (s, 3H), 1.86 (quintet, 2H, J = 6 Hz).

¹³ C NMR (CDCl ₃ , 300 MHz) δ 168.8, 146.1, 135.0, 133.8, 129.5, 119.4, 62.3, 56.19, 56.14, 55.7, 54.9, 54.5, 27.9, 20.8.

Example 90. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- methoxyphenyl) acetamide (Compound No. 90)

A target compound having a yield of 27% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.83 (bs, 1H), 8.41 (d, 1H, J = 8 Hz), 7.05-7.03 (m, 1H), 7.00 (s, 2H), 6.98-6.88 (m , 2H), 3.89 (s, 3H), 3.81 (s, 2H), 3.27 (s, 2H), 2.86-2.77 (m, 8H), 1.87 (quintet, 2H, J = 5.6 Hz).

¹³ C NMR (CDCl ₃ , 300 MHz) δ 168.9, 148.1, 146.4, 127.3, 123.7, 121.1, 119.5, 115.9, 110.0, 63.5, 56.8, 56.6, 56.1, 55.7, 55.0, 54.1, 28.0.

Example 91. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide (Compound No. 91)

A target compound having a yield of 35% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 10.0 (bs, 1H), 9.21 (bs, 1H), 7.35 (s, 1H), 7.34 (m, 1H), 7.02-6.99 (m, 3H), 6.66 ( d, 1H, J = 7.6 Hz), 3.80 (s, 3H), 3.79 (s, 2H), 3.24 (s, 2H), 2.85-2.75 (m, 8H), 1.86 (quintet, 2H, J = 6 Hz ).

Example 92. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (4- methoxyphenyl) acetamide (Compound No. 92)

A target compound having a yield of 36% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.09 (bs, 1H), 7.46 (d, 2H, J = 8.8 Hz), 6.99 (s, 2H), 6.86 (d, 2H, J = 8.8 Hz), 3.79 (s, 2H), 3.78 (s, 3H), 3.24 (s, 2H), 2.86-2.74 (m, 8H), 1.86 (quintet, 2H, J = 6 Hz).

Example 93. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - acetamide (methyl) phenyl-2- (trifluoromethyl) Amide (Compound No. 93)

A target compound having a yield of 71% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.92 (bs, 1H), 8.43 (d, 1H, J = 8.4 Hz), 7.61-7.52 (m, 2H), 7.19 (t, 1H, J = 7.8 Hz) , 6.99 (s, 2H), 3.78 (s, 2H), 3.29 (s, 2H), 2.89-2.76 (m, 8H), 1.86 (quintet, 2H, J = 6 Hz).

Example 94. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - acetamide (methyl) phenyl 3- (trifluoromethyl) Amide (Compound No. 94)

A target compound having a yield of 90% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.40 (bs, 1H), 7.87 (s, 1H), 7.81 (d, 1H, J = 7.6 Hz), 7.45-7.33 (m, 2H), 6.99 (s, 2H), 3.85 (s, 2H), 3.27 (s, 2H), 2.86-2.74 (m, 8H), 1.86 (quintet, 2H, J = 6 Hz).

Example 95. 2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide Amide (Compound No. 95)

A target compound having a yield of 53% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.42 (bs, 1H), 7.69 (d, 2H, J = 8.8 Hz), 7.59 (d, 2H, J = 8.8 Hz), 7.01 (s, 2H), 3.81 (s, 2H), 3.28 (s, 2H), 2.88-2.75 (m, 8H), 1.86 (quintet, 2H, J = 6 Hz).

Example 96. N - (2,6- diethyl-phenyl) -2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) acetamide Amide (Compound No. 96)

A target compound having a yield of 54% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.77 (bs, 1H), 7.21 (m, 1H), 7.13 (d, 2H, J = 7.6 Hz), 3.74 (s, 2H), 3.34 (s, 2H) , 2.95-2.83 (m, 8H), 2.58 (q, 4H, J = 7.6 Hz), 2.20 (s, 3H), 2.05 (s, 3H), 1.90 (quintet, 2H , J = 6 Hz), 1.18 ( t, 6H, J = 7.6 Hz).

Example 97. N- (2,4-dimethylphenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide (Compound No. 97)

A target compound having a yield of 67% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.21 (bs, 1H), 7.92 (d, 1H, J = 8 Hz), 7.02-6.96 (m, 2H), 3.74 (s, 2H), 3.30 (s, 2H), 2.89-2.84 (m, 8H), 2.30 (s, 3H), 2.25 (s, 3H), 2.24 (s, 3H), 2.05 (s, 3H), 1.90 (quintet, 2H , J = 6 Hz ).

Example 98. N- (3,4-dimethylphenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide (Compound No. 98)

A target compound having a yield of 46% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.12 (bs, 1H), 7.29 (s, 1H), 7.28 (d, 1H, J = 8 Hz), 7.05 (d, 1H, J = 8 Hz), 3.76 (s, 2H), 3.23 (s, 2H), 2.87-2.88 (m, 8H), 2.24 (s, 3H), 2.22 (s, 3H), 2.21 (s, 3H), 2.06 (s, 3H), 1.88 (quintet, 2H, J = 5.6 Hz).

Example 99. N- (2,6-dimethylphenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound No. 99)

A target compound having a yield of 46% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.75 (bs, 1H), 7.10-7.07 (m, 3H), 3.74 (s, 2H), 3.33 (s, 2H), 2.95-2.83 (m, 8H), 2.22 (s, 6H), 2.20 (s, 3H), 2.04 (s, 3H), 1.89 (quintet, 2H , J = 6 Hz).

Example 100. N- (2-Chlorophenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (compound Number 100)

The title compound was obtained in the same manner as the representative synthesis example, with a yield of 59%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.97 (bs, 1H), 8.48 (d, 1H, J = 6.8 Hz), 7.35 (d, 1H, J = 8 Hz), 7.25 (m, 1H), 7.0 (t, 1H, J = 7.6 Hz), 3.74 (s, 2H), 3.28 (s, 2H), 2.89-2.83 (m, 8H), 2.21 (s, 3H), 2.05 (s, 3H), 1.90 ( quintet, 2H , J = 6 Hz).

Example 101. N- (3-Chlorophenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound Number 101)

A target compound having a yield of 50% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.33 (bs, 1H), 7.66 (s, 1H), 7.41 (d, 1H, J = 2.4 Hz), 7.24 (m, 1H), 7.06 (t, 1H, J = 7.2 Hz), 3.76 (s, 2H), 3.24 (s, 2H), 2.86-2.83 (m, 8H), 2.21 (s, 3H), 2.05 (s, 3H), 1.86 (quintet, 2H , J = 5.6 Hz).

Example 102. N- (4-Chlorophenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound Number 102)

A target compound having a yield of 75% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.30 (bs, 1H), 7.51 (d, 2H, J = 7.2 Hz), 7.27 (d, 2H, J = 7.2 Hz), 3.74 (s, 2H), 3.23 (s, 2H), 2.85-2.79 (m, 8H), 2.20 (s, 3H), 2.05 (s, 3H), 1.86 (quintet, 2H , J = 6 Hz).

Example 103. 2- (4 - ((4,5-Dimethyl-2-yl) methyl) diazepan-1-yl) - N - acetamide (Compound No. 103) (2-fluorophenyl)

The title compound was obtained in the same manner as the representative synthesis example, yield 84%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.63 (bs, 1H), 8.36 (t, 1H, J = 8 Hz), 7.11-7.01 (m, 3H), 3.74 (s, 2H), 3.27 (s, 2H), 2.87-2.81 (m, 8H), 2.21 (s, 3H), 2.05 (s, 3H), 1.88 (quintet, 2H, J = 6 Hz).

¹³ C NMR (CDCl ₃ , 400 MHz) δ 169.2, 158.9, 153.6, 151.1, 143.6, 130.2, 126.2, 124.5, 124.1, 121.0, 114.8, 62.8, 56.1, 55.5, 55.0, 54.7, 53.6, 27.7, 11.1, 10.0 .

Example 104. 2- (4 - ((4,5-Dimethyl-2-yl) methyl) diazepan-1-yl) - N - (3- fluorophenyl) acetamide (Compound No. 104)

A target compound having a yield of 47% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.40 (bs, 1H), 7.54 (d, 1H, J = 7.6 Hz), 7.28-7.21 (m, 2H), 6.81 (t, 1H, J = 7.2 Hz) , 3.79 (s, 2H), 3.28 (s, 2H), 2.90-2.85 (m, 8H), 2.23 (s, 3H), 2.08 (s, 3H), 1.89 (quintet, 2H , J = 6 Hz).

Example 105. 2- (4 - ((4,5-Dimethyl-2-yl) methyl) diazepan-1-yl) - N - acetamide (Compound No. 105) (4-fluorophenyl)

A target compound having a yield of 54% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.27 (bs, 1H), 7.54-7.51 (m, 2H), 7.0 (d, 2H, J = 7.2 Hz), 3.76 (s, 2H), 3.25 (s, 2H), 2.87-2.81 (m, 8H), 2.21 (s, 3H), 2.06 (s, 3H), 1.87 (quintet, 2H , J = 6 Hz).

Example 106. 2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - o -tolyl setamide (Compound No. 106)

The title compound was obtained in the same manner as the representative synthesis example, yield 64%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.3 (bs, 1H), 8.11 (d, 1H, J = 8 Hz), 7.19-7.14 (m, 2H), 7.01 (t, 1H, J = 6.4 Hz) , 3.72 (s, 2H), 3.27 (s, 2H), 2.88-2.83 (m, 8H), 2.25 (s, 3H), 2.20 (s, 3H), 2.04 (s, 3H), 1.87 (quintet, 2H , J = 6 Hz).

Example 107. 2- (4-((4,5-Dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide (Compound No. 107)

A target compound having a yield of 45% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.19 (bs, 1H), 7.4 (s, 1H), 7.33 (d, 1H, J = 8 Hz), 7.19 (t, 1H, J = 7.8 Hz), 6.91 (d, 1H, J = 7.6 Hz), 3.75 (s, 2H), 3.23 (s, 2H), 2.86-2.82 (m, 8H), 2.33 (s, 3H), 2.21 (s, 3H), 2.05 ( s, 3H), 1.86 (quintet, 2H , J = 6 Hz).

Example 108. 2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - p -tolylacetamide (Compound No. 108)

A target compound having a yield of 33% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.18 (bs, 1H), 7.44 (d, 2H, J = 6.8 Hz), 7.12 (d, 2H, J = 8 Hz), 3.75 (s, 2H), 3.23 (s, 2H), 2.87-2.83 (m, 8H), 2.30 (s, 3H), 2.22 (s, 3H), 2.06 (s, 3H), 1.87 (quintet, 2H , J = 6 Hz)

Example 109. 2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) -N -2-methoxyphenyl) acetamide (compound Number 109)

The title compound was obtained in the same manner as the representative synthesis example above, with a yield of 64%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.82 (bs, 1H), 8.40 (d, 1H, J = 6.4 Hz), 7.06-6.97 (m, 2H), 6.89 (d, 1H, J = 8 Hz) , 3.88 (s, 3H), 3.75 (s, 2H), 3.26 (s, 2H), 2.91-2.81 (m, 8H), 2.22 (s, 3H), 2.06 (s, 3H), 1.89 (quintet, 2H , J = 6 Hz).

Example 110. 2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide ( Compound number 110)

A target compound having a yield of 50% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.24 (bs, 1H), 7.36 (s, 1H), 7.20 (t, 1H, J = 8 Hz), 7.0 (d, 1H, J = 6.4 Hz), 6.65 (d, 1H, J = 7.8 Hz), 3.83 (s, 3H), 3.75 (s, 2H), 3.26 (s, 2H), 2.86-2.82 (m, 8H), 2.21 (s, 3H), 2.05 ( s, 3H), 1.86 (quintet, 2H , J = 6 Hz).

Example 111. 2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- methoxyphenyl) acetamide ( Compound no.111)

A target compound having a yield of 53% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.13 (bs, 1H), 7.46 (d, 2H, J = 6.8 Hz), 6.86 (d, 2H, J = 6.8 Hz), 3.80 (s, 3H), 3.75 (s, 2H), 3.23 (s, 2H), 2.86-2.82 (m, 8H), 2.23 (s, 3H), 2.07 (s, 3H), 1.86 (quintet, 2H , J = 6 Hz).

Example 112. 2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl Acetamide (Compound No. 112)

A target compound having a yield of 70% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.93 (bs, 1H), 8.42 (d, 1H, J = 8.4 Hz), 7.59-7.51 (m, 2H), 7.17 (t, 1H, J = 7.8 Hz) , 3.72 (s, 2H), 3.27 (s, 2H), 2.86-2.84 (m, 8H), 2.21 (s, 3H), 2.05 (s, 3H), 1.87 (quintet, 2H , J = 6 Hz).

Example 113. 2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl Acetamide (Compound No. 113)

The target compound was obtained in the yield 66% by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.48 (bs, 1H), 7.87 (s, 1H), 7.81 (d, 1H, J = 8 Hz), 7.44 (t, 1H, J = 8 Hz), 7.35 (d, 1H, J = 8 Hz), 3.79 (s, 2H), 3.30 (s, 2H), 2.90-2.84 (m, 8H), 2.22 (s, 3H), 2.05 (s, 3H), 1.90 ( quintet, 2H , J = 6 Hz).

Example 114

2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide ( Compound number 114)

The title compound was obtained in the same manner as the representative synthesis example, with a yield of 85%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.50 (bs, 1H), 7.70 (d, 2H, J = 8 Hz), 7.54 (d, 2H, J = 8.8 Hz), 3.76 (s, 2H), 3.27 (s, 2H), 2.87-2.84 (m, 8H), 2.21 (s, 3H), 2.06 (s, 3H), 1.87 (quintet, 2H , J = 6 Hz).

Example 115. N- (2,6-diethylphenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1- Acetamide (Compound No. 115)

The title compound was obtained in the same manner as the representative synthesis example, yield 44%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.76 (bs, 1H), 7.61 (dd, 1H, J = 8.8 Hz), 7.20 (d, 2H, J = 6.4 Hz), 7.14-7.07 (m, 3H) , 4.02 (s, 2H), 3.36 (s, 2H), 2.97-2.89 (m, 8H), 2.57 (q, 4H, J = 7.6 Hz), 1.93 (quintet, 2H, J = 5.8 Hz), 1.17 ( t, 6H, J = 7.6 Hz).

Example 116. N- (2,4-dimethylphenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl Acetamide (Compound No. 116)

The title compound was obtained in the same manner as the representative synthesis example, with a yield of 62%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.19 (bs, 1H), 7.94 (d, 1H, J = 8.0 Hz), 7.64 (dd, 1H, J = 8.8 Hz), 7.25 (m, 1H), 7.10 (t, 1H, J = 8.8 Hz), 7.03 (d, 1H, J = 8.4 Hz), 6.98 (s, 1H), 4.02 (s, 2H), 3.30 (s, 2H), 2.98-2.89 (m, 8H), 2.29 (s, 3H), 2.20 (s, 3H), 1.92 (quintet, 2H, J = 5.8 Hz).

Example 117. N- (3,4-dimethylphenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl Acetamide (Compound No. 117)

A target compound having a yield of 86% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.09 (bs, 1H), 7.65 (dd, 1H, J = 8.8 Hz), 7.34 (s, 1H), 7.27-7.24 (m, 3H), 7.12-7.05 ( m, 2H), 4.04 (s, 2H), 3.26 (s, 2H), 2.98-2.86 (m, 8H), 2.24 (s, 3H), 2.22 (s, 3H), 1.91 (quintet, 2H, J = 6.0 Hz).

Example 118. N- (2,6-dimethylphenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl Acetamide (Compound No. 118)

A target compound having a yield of 38% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.73 (bs, 1H), 7.61 (dd, 1H , J = 8.8 Hz), 7.23 (d, 1H, J = 7.8 Hz), 7.11-7.05 (m, 4H) , 4.02 (s, 2H), 3.34 (s, 2H), 2.96-2.93 (m, 8H), 2.21 (s, 6H), 1.92 (quintet, 2H, J = 6.0 Hz).

Example 119. N- (2-Chlorophenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acet Amide (Compound No. 119)

A target compound having a yield of 93% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.96 (bs, 1H), 8.49 (dd, 1H, J = 8.0 Hz), 7.65 (dd, 1H, J = 5.2 Hz), 7.35 (dd, 1H, J = 8.0 Hz), 7.27-7.23 (m, 2H), 7.10-6.99 (m, 2H), 4.02 (s, 2H), 3.30 (s, 2H), 3.0-2.87 (m, 8H), 1.95 (quintet, 2H , J = 6.0 Hz).

Example 120. N- (3-Chlorophenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) acet Amide (Compound No. 120)

A target compound having a yield of 73% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.27 (bs, 1H), 7.67 (t, 1H, J = 2.0 Hz), 7.65 (dd, 1H, J = 5.2 Hz), 7.47-7.37 (m, 1H) , 7.25-7.20 (m, 2H), 7.10-7.04 (m, 2H), 4.03 (s, 2H), 3.26 (s, 2H), 2.97-2.85 (m, 8H), 1.91 (quintet, 2H, J = 6.0 Hz).

Example 121. N- (4-Chlorophenyl) -2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) acet Amide (Compound No. 121)

A target compound having a yield of 35% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.27 (bs, 1H), 7.65 (dd, 1H, J = 4.8 Hz), 7.52-7.48 (m, 2H), 7.28-7.24 (m, 3H), 7.12- 7.07 (m, 1H), 4.04 (s, 2H), 3.26 (s, 2H), 2.98-2.86 (m, 8H), 1.92 (quintet, 2H, J = 6.0 Hz).

Example 122. 2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-fluorophenyl) Acetamide (Compound No. 122)

A target compound having a yield of 31% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.33 (bs, 1H), 8.40 (t, 1H, J = 8.0 Hz), 7.65 (dd, 1H, J = 5.2 Hz), 7.27-7.24 (m, 1H) , 7.11-7.01 (m, 4H), 4.03 (s, 2H), 3.30 (s, 2H), 2.99-2.87 (m, 8H), 1.96 (quintet, 2H, J = 6.0 Hz).

Example 123. 2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3-fluorophenyl) Acetamide (Compound No. 123)

A target compound having a yield of 45% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.32 (bs, 1H), 7.64 (dd, 1H, J = 4.8 Hz), 7.54 (dt, 1H, J = 2.4 Hz), 7.25-7.14 (m, 3H) , 7.10-7.05 (m, 1H), 6.80-6.75 (m, 1H), 4.03 (s, 2H), 3.26 (s, 2H), 2.97-2.85 (m, 8H), 1.91 (quintet, 2H, J = 5.6 Hz).

Example 124. 2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4-fluorophenyl) Acetamide (Compound No. 124)

A target compound having a yield of 82% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.21 (bs, 1H), 7.64 (dd, 1H, J = 4.8 Hz), 7.51 (dd, 2H, J = 4.8 Hz), 7.25 (dd, 1H, J = 5.6 Hz), 7.1-7.05 (m, 1H), 7.0-6.96 (m, 2H), 4.03 (s, 2H), 3.25 (s, 2H), 2.95-2.85 (m, 8H), 1.96 (quintet, 2H , J = 6.0 Hz).

Example 125. 2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide (compound Number 125)

A target compound having a yield of 75% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.16 (bs, 1H), 8.12 (d, 1H, J = 7.6 Hz), 7.64 (dd, 1H, J = 4.8 Hz), 7.24-7.0 (m, 5H) , 4.01 (s, 2H), 3.30 (s, 2H), 2.97-2.86 (m, 8H), 2.23 (s, 3H), 1.93 (quintet, 2H, J = 6.0 Hz).

Example 126. 2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide (compound Number 126)

A target compound having a yield of 52% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.17 (bs, 1H), 7.64 (dd, 1H, J = 5.2 Hz), 7.40 (s, 1H), 7.32 (d, 1H, J = 8.0 Hz), 7.25 (dd, 1H, J = 8.0 Hz), 7.19 (t, 1H, J = 8.0 Hz), 7.10 (m, 1H), 6.91 (d, 1H, J = 7.6 Hz), 4.03 (s, 2H), 3.29 (s, 2H), 2.97-2.85 (m, 8H), 2.40 (s, 3H), 1.92 (quintet, 2H, J = 6.0 Hz).

Example 127. 2- (4-((6-fluorobenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide (compound Number 127)

The title compound was obtained in the same manner as the representative synthesis example, with a yield of 59%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.15 (bs, 1H), 7.64 (dd, 1H, J = 4.8 Hz), 7.43 (d, 2H, J = 8.0 Hz), 7.25 (dd, 1H, J = 8.0 Hz), 7.10-7.05 (m, 3H), 4.03 (s, 2H), 3.24 (s, 2H), 2.97-2.85 (m, 8H), 2.29 (s, 3H), 1.91 (quintet, 2H, J = 6.0 Hz).

Example 128. 2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-methoxyphenyl) Acetamide (Compound No. 128)

A target compound having a yield of 67% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.76 (bs, 1H), 8.40 (dd, 1H, J = 8.0 Hz), 7.64 (dd, 1H, J = 4.8 Hz), 7.26 (dd, 1H, J = 8.0 Hz), 7.08-6.95 (m, 3H), 6.87 (dd, 1H, J = 8.0 Hz), 4.03 (s, 2H), 3.83 (s, 3H), 3.27 (s, 3H), 3.00-2.84 ( m, 8H), 1.94 (quintet, 2H, J = 6.0 Hz).

Example 129. 2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) Acetamide (Compound No. 129)

The title compound was obtained in the same manner as the representative synthesis example, with a yield of 59%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.22 (bs, 1H), 7.64 (dd, 1H, J = 4.8 Hz), 7.35 (t, 1H, J = 2.4 Hz), 7.25-7.15 (m, 2H) , 7.10-7.05 (m, 1H), 6.99-6.96 (m, 1H), 6.65-6.62 (m, 1H), 4.04 (s, 2H), 3.79 (s, 3H), 3.25 (s, 2H), 2.96 -2.84 (m, 8 H), 1.91 (quintet, 2 H, J = 6.0 Hz).

Example 130. 2- (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- methoxyphenyl) Acetamide (Compound No. 130)

A target compound having a yield of 32% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.11 (bs, 1H), 7.65 (dd, 1H, J = 4.8 Hz), 7.46-7.42 (m, 2H), 7.26 (dd, 1H, J = 8.0 Hz) , 7.11-7.06 (m, 1H), 6.86-6.82 (m, 2H), 4.03 (s, 2H), 3.78 (s, 3H), 3.27 (s, 2H), 2.97-2.86 (m, 8H), 1.92 (quintet, 2H, J = 5.6 Hz).

Example 131. 2- (2- (trifluoromethyl - (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N Methyl) phenyl) acetamide (Compound No. 131)

A target compound having a yield of 47% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.90 (bs, 1H), 8.34 (d, 1H, J = 8.4 Hz), 7.62-7.49 (m, 3H), 7.23 (dd, 1H, J = 8.0 Hz) , 7.16 (t, 1H, J = 7.6 Hz), 7.05-7.02 (m, 1H), 3.99 (s, 2H), 3.27 (s, 2H), 2.95-2.85 (m, 8H), 1.92 (quintet, 2H , J = 5.6 Hz).

Example 132. 2- (3- (trifluoro - (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N Methyl) phenyl) acetamide (Compound No. 132)

A target compound having a yield of 34% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.41 (bs, 1H), 7.85 (s, 1H), 7.69 (d, 1H, J = 8.0 Hz), 7.65 (dd, 1H, J = 8.4 Hz), 7.39 (t, 1H, J = 8.0 Hz), 7.35 (d, 1H, J = 8.0 Hz), 7.25 (dd, 1H, J = 5.6 Hz), 7.11-7.06 (m, 1H), 4.04 (s, 2H) , 3.29 (s, 2H), 2.98-2.87 (m, 8H), 1.94 (quintet, 2H, J = 6.0 Hz).

Example 133. 2- (4- (trifluoromethyl - (4 - ((6-fluoro-benzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N Methyl) phenyl) acetamide (Compound No. 133)

A target compound having a yield of 67% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.45 (bs, 1H), 7.68-7.62 (m, 3H), 7.56 (d, 2H, J = 8.8 Hz), 7.26 (dd, 1H, J = 8.0 Hz) , 7.12-7.07 (m, 1H), 4.05 (s, 2H), 3.29 (s, 2H), 2.99-2.87 (m, 8H), 1.93 (quintet, 2H, J = 6.0 Hz).

Example 134. N- (2,6-diethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl Acetamide (Compound No. 134)

The title compound was obtained in the same manner as the representative synthesis example, yield 94%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 10.0 (bs, 1H), 8.79 (bs, 1H), 7.83 (d, 2H, J = 7.6 Hz), 7.39-7.33 (m, 3H), 7.23-7.20 ( m, 1H), 7.13 (d, 2H, J = 7.6 Hz), 7.0-6.9 (m, 1H), 4.13 (s, 2H), 3.34 (s, 2H), 2.94-2.78 (m, 8H), 2.60 (q, 4H, J = 7.6 Hz), 1.88 (quintet, 2H, J = 3.2 Hz), 1.20 (t, 6H, J = 7.6 Hz).

Example 135. N- (2,4-dimethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepane-1-yl) Acetamide (Compound No. 135)

A target compound having a yield of 82% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.20 (bs, 1H), 7.90 (d, 2H, J = 6.8 Hz), 7.72 (d, 1H, J = 8.0 Hz), 7.40-7.32 (m, 3H) , 7.10 (s, 1H), 6.99-6.96 (m, 2H), 3.88 (s, 2H), 3.30 (s, 2H), 2.96-2.86 (m, 8H), 2.26 (s, 3H), 2.21 (s , 3H), 1.98 (quintet, 2H, J = 5.6 Hz).

Example 136. N- (3,4-dimethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepane-1-yl) Acetamide (Compound No. 136)

A target compound having a yield of 75% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.21 (bs, 1H), 7.83 (d, 2H, J = 7.2 Hz), 7.41-7.27 (m, 5H), 7.06-6.99 (m, 2H), 3.73 ( s, 2H), 3.34 (s, 2H), 2.86-2.81 (m, 8H), 2.24 (s, 3H), 2.22 (s, 3H), 1.88 (quintet, 2H, J = 5.6 Hz).

Example 137. N- (2,6-dimethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) Acetamide (Compound No. 137)

A target compound having a yield of 74% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 8.80 (bs, 1H), 7.84 (d, 2H, J = 6.9 Hz), 7.40-7.32 (m, 3H), 7.10-7.06 (m, 3H), 6.93 ( s, 1H), 3.67 (s, 2H), 3.33 (s, 2H), 2.93-2.78 (m, 8H), 2.21 (s, 6H), 1.88 (quintet, 2H, J = 5.4 Hz).

Example 138. N- (2-Chlorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound No. 138)

A target compound having a yield of 93% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.97 (bs, 1H), 8.47 (dd, 1H, J = 8.0 Hz), 7.86 (d, 2H, J = 7.6 Hz), 7.36-7.23 (m, 5H) , 7.04 (dt, 1H, J = 7.8 Hz), 6.97 (s, 1H), 3.69 (s, 2H), 3.26 (s, 2H), 2.85-2.79 (m, 8H), 1.89 (quintet, 2H, J = 6.0 Hz).

Example 139. N- (3-Chlorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound No. 139)

A target compound having a yield of 81% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.38 (bs, 1H), 7.85-7.83 (m, 2H), 7.71 (t, 2H, J = 2.0 Hz), 7.44-7.31 (m, 4H), 7.22 ( t, 1H, J = 8.4 Hz), 7.07 (d, 1H, J = 8.0 Hz), 6.99 (s, 1H), 3.72 (s, 2H), 3.29 (s, 2H), 2.88-2.80 (m, 8H ), 1.87 (quintet, 2H, J = 3.6 Hz).

Example 140 N- (4-chlorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide (Compound No. 140)

A target compound having a yield of 74% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.36 (bs, 1H), 7.85 (dd, 2H, J = 8.0 Hz), 7.54-7.50 (m, 2H),, 7.39-7.32 (m, 3H), 7.23 (d, 2H, J = 8.4 Hz), 6.97 (s, 1H), 3.70 (s, 2H), 3.23 (s, 2H), 2.88-2.77 (m, 8H), 1.85 (quintet, 2H, J = 6.0 Hz).

Example 141. N - (2-fluorophenyl) -2- (4 - ((2-phenyl -1 H-imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide Amide (Compound No. 141)

A target compound having a yield of 98% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.69 (bs, 1H), 8.40 (t, 1H, J = 8.0 Hz), 7.87 (d, 2H, J = 7.6 Hz), 7.35-7.30 (m, 3H) , 7.14-7.02 (m, 3H), 6.98 (s, 1H), 3.68 (s, 2H), 3.26 (s, 2H), 2.83-2.77 (m, 8H), 1.86 (quintet, 2H, J = 6.0 Hz ).

Example 142 N- (3-fluorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acet Amide (Compound No. 142)

The title compound was obtained in the same manner as the representative synthesis example, with a yield of 56%.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.43 (bs, 1H), 7.86 (dd, 2H, J = 6.6 Hz), 7.59-7.55 (m, 1H), 7.42-7.31 (m, 3H), 7.22 ( m, 2H), 6.99 (s, 1H), 6.82-6.76 (m, 1H), 3.47 (s, 2H), 3.26 (s, 2H), 2.85-2.80 (m, 8H), 1.88 (quintet, 2H, J = 5.7 Hz).

Example 143. N- (4-fluorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acet Amide (Compound No. 143)

A target compound having a yield of 42% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.35 (bs, 1H), 7.86 (t, 2H, J = 7.2 Hz), 7.57 (dd, 2H, J = 8.7 Hz), 7.42-7.32 (m, 3H) , 6.98-6.94 (m, 3H), 3.71 (s, 2H), 3.26 (s, 2H), 2.85-2.78 (m, 8H), 1.89 (quintet, 2H, J = 5.4 Hz).

Example 144. 2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide (Compound No. 144)

A target compound having a yield of 57% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.32 (bs, 1H), 8.09 (d, 2H, J = 8.0 Hz), 7.85 (d, 2H, J = 7.2 Hz), 7.40-7.31 (m, 3H) , 7.21 (t, 1H, J = 7.6 Hz), 7.17 (d, 1H, J = 7.2 Hz), 7.06 (dt, 1H, J = 7.2 Hz), 6.97 (s, 1H), 3.70 (s, 2H) , 3.28 (s, 2H), 2.89-2.81 (m, 8H), 2.27 (s, 3H), 1.89 (quintet, 2H, J = 6.0 Hz).

Example 145. 2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide (Compound No. 145)

The title compound was obtained in the same manner as the representative synthesis example above, with a yield of 64%.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.27 (bs, 1H), 7.88 (d, 2H, J = 8.1 Hz), 7.43 (s, 1H), 7.36-7.29 (m, 4H), 7.20 (t, 1H, J = 7.8 Hz), 6.97 (s, 1H), 6.93 (d, 1H, J = 7.5 Hz), 3.70 (s, 2H), 3.22 (s, 2H), 2.82-2.76 (m, 8H), 2.33 (s, 3 H), 1.83 (quintet, 2 H, J = 5.7 Hz).

Example 146. 2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) -N - p -tolylacetamide (Compound No. 146)

The target compound was obtained in the yield 66% by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.24 (bs, 1H), 7.85 (d, 2H, J = 7.2 Hz), 7.46 (d, 2H, J = 8.0 Hz), 7.39-7.30 (m, 3H) , 7.10 (d, 2H, J = 8.0 Hz), 6.97 (s, 1H), 3.70 (s, 2H), 3.23 (s, 2H), 2.88-2.78 (m, 8H), 2.30 (s, 3H), 1.86 (quintet, 2H, J = 6.0 Hz).

Example 147. N- (2-methoxyphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acet Amide (Compound No. 147)

A target compound having a yield of 76% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.85 (bs, 1H), 8.42 (dd, 1H, J = 8.0 Hz), 7.85 (d, 2H, J = 8.0 Hz), 7.38-7.30 (m, 3H) , 7.10-6.94 (m, 3H), 6.89 (dd, 1H, J = 8.0 Hz), 3.86 (s, 3H), 3.72 (s, 2H), 3.25 (s, 2H), 2.84-2.78 (m, 8H ), 1.87 (quintet, 2H, J = 5.6 Hz).

Example 148. N- (3-methoxyphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acet Amide (Compound No. 148)

A target compound having a yield of 61% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.33 (bs, 1H), 7.87 (d, 2H, J = 6.9 Hz), 7.38-7.30 (m, 4H), 7.21 (t, 1H, J = 8.1 Hz) , 6.98 (s, 1H), 6.67 (dd, 1H, J = 8.1 Hz), 3.79 (s, 3H), 3.70 (s, 2H), 3.23 (s, 2H), 2.83-2.77 (m, 8H), 1.84 (quintet, 2H, J = 5.7 Hz).

Example 149. N- (4-methoxyphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acet Amide (Compound No. 149)

A target compound having a yield of 68% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.20 (bs, 1H), 7.88 (dd, 2H, J = 6.6 Hz), 7.50 (d, 2H, J = 9.0 Hz), 7.39-7.29 (m, 3H) , 6.97 (s, 1H), 6.84 (d, 2H, J = 8.7 Hz), 3.80 (s, 3H), 3.70 (s, 2H), 3.23 (s, 2H), 2.84-2.77 (m, 8H), 1.86 (quintet, 2H, J = 6.0 Hz).

Example 150. 2- (4 - ((2-phenyl -1 H-imidazol-5-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl ) Phenyl) acetamide (Compound No. 150)

A target compound having a yield of 68% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.95 (bs, 1H), 8.43 (d, 1H, J = 8.4 Hz), 7.86 (dd, 2H, J = 8.8 Hz), 7.61 (d, 1H, J = 8.0 Hz), 7.56 (t, 1H, J = 8.0 Hz), 7.38-7.30 (m, 3H), 7.20 (t, 1H, J = 7.6 Hz), 6.98 (s, 1H), 3.68 (s, 2H) , 3.26 (s, 2H), 2.86-2.78 (m, 8H), 1.87 (quintet, 2H, J = 6.0 Hz).

Example 151. 2- (4 - ((2-phenyl -1 H-imidazol-5-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl ) Phenyl) acetamide (Compound No. 151)

A target compound having a yield of 88% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.50 (bs, 1H), 7.90 (s, 1H), 7.86 (d, 2H, J = 7.2 Hz), 7.76 (d, 1H, J = 7.6 Hz), 7.40 -7.29 (m, 5H), 6.97 (s, 1H), 3.70 (s, 2H), 3.25 (s, 2H), 2.83-2.76 (m, 8H), 1.85 (quintet, 2H, J = 6.0 Hz).

Example 152. 2- (4 - ((2-phenyl -1 H-imidazol-5-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl ) Phenyl) acetamide (Compound No. 152)

A target compound having a yield of 75% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.56 (bs, 1H), 7.86 (d, 2H, J = 7.6 Hz), 7.70 (d, 2H, J = 8.4 Hz), 7.50 (d, 1H, J = 8.0 Hz), 7.38-7.28 (m, 4H), 6.97 (s, 1H), 3.70 (s, 2H), 3.21 (s, 2H), 2.87-2.75 (m, 8H), 1.86 (quintet, 2H, J = 6.0 Hz).

Example 153. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2,6- diethyl-phenyl) acetamide (Compound No. 153 )

Bis in the same manner as in the representative synthesis example 4 (4-fluorophenyl) methyl chloride (50 mg, 0.209 mmol) and 2- (1,4-diazepan-1-yl) - N - (2,6- di Ethylphenyl) acetamide (79 mg, 0.272 mmol) was stirred in acetonitrile solvent in the presence of K ₂ CO ₃ (145 mg, 1.047 mmol) to give 30 mg (28%) of the title compound.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.84 (bs, 1H), 7.37 (dd, 4H, J = 8.4 Hz), 7.25 (m, 1H), 7.15 (d, 2H, J = 7.6 Hz), 6.99 (t, 4H, J = 8.8 Hz), 4.59 (s, 1H), 3.38 (s, 2H), 3.03 (t, 2H, J = 5.6 Hz), 2.89 (m, 2H), 2.69-2.66 (m, 4H), 2.60 (q, 4H, J = 7.6 Hz), 1.85 (quintet, 2H, J = 5.6 Hz), 1.20 (t, 6H, J = 7.6 Hz).

Example 154. 2- (4- (bis (phenyl) methyl) 4-fluoro-1, 4-diazepan-l-yl) - N - (2,4- dimethylphenyl) acetamide (Compound No. 154)

The target compound was obtained in the yield 58% by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.24 (bs, 1H), 7.95 (d, 1H, J = 8.0 Hz), 7.36 (m, 4H), 7.04 (m, 6H), 4.60 (s, 1H) , 3.31 (s, 2H), 2.96 (t, 2H, J = 6.0 Hz), 2.83-2.81 (m, 2H), 2.69-2.66 (m, 4H), 2.29 (s, 3H), 2.23 (s, 3H ), 1.85 (quintet, 2H, J = 6.0 Hz).

Example 155. 2- (4- (bis (phenyl) methyl) 4-fluoro-1, 4-diazepan-l-yl) - N - (3,4- dimethylphenyl) acetamide (Compound No. 155)

A target compound having a yield of 25% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.15 (bs, 1H), 7.37-7.33 (m, 4H), 7.28 (dd, 1H, J = 8.0 Hz), 7.09 (d, 1H, J = 8.0 Hz) , 7.02-6.96 (m, 4H), 4.62 (s, 1H), 3.26 (s, 2H), 2.92 (t, 2H, J = 6.0 Hz), 2.80-2.77 (m, 2H), 2.70-2.65 (m , 4H), 2.25 (s, 3H), 2.22 (s, 3H), 1.82 (quintet, 2H, J = 6.0 Hz).

Example 156. 2- (4- (bis (phenyl) methyl) 4-fluoro-1, 4-diazepan-l-yl) - N - (2,6- dimethylphenyl) acetamide (Compound No. 156)

The target compound was obtained in the yield 58% by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 8.83 (bs, 1H), 7.37-7.34 (m, 4H), 7.11-7.09 (m, 3H), 7.00-6.95 (m, 4H), 4.59 (s, 1H ), 3.38 (s, 2H), 3.03 (t, 2H, J = 6.0 Hz), 2.90-2.87 (m, 2H), 2.70-2.66 (m, 4H), 2.23 (s, 6H), 1.85 (quintet, 2H, J = 6.0 Hz).

Example 157. 2- (4- (bis (phenyl) methyl) 4-fluoro-1, 4-diazepan-l-yl) - N - (2-chlorophenyl) acetamide (Compound No. 157)

A target compound having a yield of 81% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 10.02 (bs, 1H), 8.50 (d, 1H, J = 8.0 Hz), 7.38-7.32 (m, 5H), 7.05-6.95 (m, 6H), 4.60 ( s, 1H), 3.32 (s, 2H), 2.94 (t, 2H, J = 6.0 Hz), 2.81-2.79 (m, 2H), 2.72-2.69 (m, 4H), 1.86 (quintet, 2H, J = 6.0 Hz).

Example 158. 2- (4- (bis (phenyl) methyl) 4-fluoro-1, 4-diazepan-l-yl) - N - (3- chlorophenyl) acetamide (Compound No. 158)

A target compound having a yield of 51% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.34 (bs, 1H), 7.65 (t, 1H, J = 2.0 Hz), 7.42 (dt, 1H, J = 4.0 Hz), 7.37 (dd, 4H, J = 8.4 Hz), 7.24 (d, 1H, J = 8.0 Hz), 7.09 (dt, 1H, J = 4.0 Hz), 7.01 (t, 4H, J = 8.8 Hz), 4.62 (s, 1H), 3.28 (s , 2H), 2.92 (t, 2H, J = 6.0 Hz), 2.81-2.78 (m, 2H), 2.69-2.65 (m, 4H), 1.83 (quintet, 2H, J = 6.0 Hz).

Example 159. 2- (4- (bis (phenyl) methyl) 4-fluoro-1, 4-diazepan-l-yl) - N - (4-chlorophenyl) acetamide (Compound No. 159)

A target compound having a yield of 68% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.29 (bs, 1H), 7.50 (d, 2H, J = 8.8 Hz), 7.36-7.28 (m, 4H), 7.05-6.96 (m, 6H), 4.62 ( s, 1H), 3.27 (s, 2H), 2.93 (t, 2H, J = 6.0 Hz), 2.81-2.78 (m, 2H), 2.69-2.64 (m, 4H), 1.83 (quintet, 2H, J = 6.0 Hz).

Example 160. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - acetamide (Compound No. 160) (2-fluorophenyl)

A target compound having a yield of 79% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.70 (bs, 1H), 8.40 (dd, 1H, J = 8.0 Hz), 7.38 (dd, 4H, J = 8.8 Hz), 7.16-6.95 (m, 7H) , 4.61 (s, 1H), 3.31 (s, 2H), 2.92 (t, 2H, J = 6.0 Hz), 2.80-2.77 (m, 2H), 2.71-2.67 (m, 4H), 1.83 (quintet, 2H , J = 6.0 Hz).

Example 161. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - acetamide (Compound No. 161) (3-fluorophenyl)

A target compound having a yield of 53% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.35 (bs, 1H), 7.53 (dt, 1H, J = 2.0 Hz), 7.36 (dd, 4H, J = 8.8 Hz), 7.30-7.24 (m, 1H) , 7.16 (d, 1H, J = 7.6 Hz), 7.01-7.96 (m, 4H), 6.83-6.78 (m, 1H), 4.62 (s, 1H), 3.28 (s, 2H), 2.93 (t, 2H , J = 6.0 Hz), 2.81-2.78 (m, 2H), 2.69-2.65 (m, 4H), 1.85 (quintet, 2H, J = 6.0 Hz).

Example 162. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (4-fluorophenyl) acetamide (Compound No. 162)

A target compound having a yield of 82% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.25 (bs, 1H), 7.51 (dd, 2H, J = 8.8 Hz), 7.36 (dd, 4H, J = 8.8 Hz), 7.04-6.96 (m, 6H) , 4.62 (s, 1H), 3.28 (s, 2H), 2.93 (t, 2H, J = 6.0 Hz), 2.81-2.79 (m, 2H), 2.69-2.64 (m, 4H), 1.85 (quintet, 2H , J = 6.0 Hz).

Example 163. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide (Compound No. 163)

A target compound having a yield of 81% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.35 (bs, 1H), 8.15 (d, 1H, J = 8.0 Hz), 7.37-7.33 (m, 4H), 7.23-7.17 (m, 2H), 7.06 ( t, 1H, J = 7.2 Hz), 6.98 (m, 4H), 4.60 (s, 1H), 3.32 (s, 2H), 2.97 (t, 2H, J = 6.0 Hz), 2.84-2.82 (m, 2H ), 2.70-2.69 (m, 4H), 2.28 (s, 3H), 1.85 (quintet, 2H, J = 6.0 Hz).

Example 164. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide (Compound No. 164)

A target compound having a yield of 80% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.22 (bs, 1H), 7.40-7.31 (m, 6H), 7.24 (t, 1H, J = 7.6 Hz), 7.01-6.96 (m, 4H), 6.94 ( d, 1H, J = 7.6 Hz), 4.61 (s, 1H), 3.28 (s, 2H), 2.93 (t, 2H, J = 6.0 Hz), 2.81-2.78 (m, 2H), 2.70-2.65 (m , 4H), 2.35 (s, 3H), 1.83 (quintet, 2H, J = 6.0 Hz).

Example 165. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide (Compound No. 165)

The target compound was obtained in the yield 58% by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.24 (bs, 1H), 7.44 (d, 2H, J = 8.4 Hz), 7.37 (dd, 4H, J = 8.4 Hz), 7.15 (d, 2H, J = 8.4 Hz), 7.00 (t, 4H, J = 8.4 Hz), 4.62 (s, 1H), 3.29 (s, 2H), 2.93 (t, 2H, J = 6.0 Hz), 2.81 (m, 2H), 2.69 -2.65 (m, 4H), 2.32 (s, 3H), 1.84 (quintet, 2H, J = 6.0 Hz).

Example 166. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2-methoxyphenyl) acetamide (Compound No. 166)

A target compound having a yield of 90% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.83 (bs, 1H), 8.41 (dd, 1H, J = 8.0 Hz), 7.38 (dd, 4H, J = 8.4 Hz), 7.05-76.87 (m, 7H) , 4.62 (s, 1H), 3.84 (s, 3H), 3.28 (s, 2H), 2.92 (t, 2H, J = 6.0 Hz), 2.78-2.66 (m, 6H), 1.85 (quintet, 2H, J = 6.0 Hz).

Example 167. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide (Compound No. 167)

A target compound having a yield of 43% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.29 (bs, 1H), 7.37-7.34 (m, 5H), 7.24 (t, 1H, J = 8.0 Hz), 7.01-6.96 (m, 5H), 6.68 ( dd, 1H, J = 8.0 Hz), 4.62 (s, 1H), 3.81 (s, 3H), 3.28 (s, 2H), 2.93 (t, 2H, J = 6.0 Hz), 2.81-2.79 (m, 2H ), 2.70-2.65 (m, 4H), 1.84 (quintet, 2H, J = 6.0 Hz).

¹³ C NMR (CDCl ₃ , 400 MHz) δ 169.1, 163.0, 160.5, 160.2, 138.8, 138.5, 129.7, 129.29, 129.21, 115.5, 115.3, 111.4, 109.8, 105.1, 73.8, 62.0, 57.1, 55.3, 54.6, 53.7 , 52.3, 28.4.

Example 168. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (4-methoxyphenyl) acetamide (Compound No. 168)

A target compound having a yield of 43% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.18 (bs, 1H), 7.46 (d, 2H, J = 8.4 Hz), 7.37-7.30 (m, 4H), 7.00-6.96 (m, 4H), 6.88 ( d, 2H, J = 8.4 Hz), 4.62 (s, 1H), 3.83 (s, 3H), 3.28 (s, 2H), 2.93-2.92 (m, 2H), 2.81 (m, 2H), 2.69 (m , 4H), 1.83 (quintet, 2H, J = 6.0 Hz).

Example 169. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (methyl) phenyl-2- (trifluoromethyl) acetamide (Compound Number 169)

A target compound having a yield of 40% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 10.00 (bs, 1H), 8.46 (t, 1H, J = 8.4 Hz), 7.62 (d, 1H, J = 8.0 Hz), 7.57 (t, 1H, J = 7.6 Hz), 7.37 (dd, 4H, J = 8.4 Hz), 7.21 (t, 1H, J = 7.6 Hz), 7.00 (t, 4H, J = 8.4 Hz), 4.59 (s, 1H), 3.32 (s , 2H), 2.95 (t, 2H, J = 6.0 Hz), 2.82-2.79 (m, 2H), 2.69-2.66 (m, 4H), 1.85 (quintet, 2H, J = 6.0 Hz).

Example 170. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (methyl) phenyl 3- (trifluoromethyl) acetamide (Compound Number 170)

A target compound having a yield of 32% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.44 (bs, 1H), 7.82 (s, 1H), 7.79 (d, 1H, J = 8.4 Hz), 7.47 (t, 2H, J = 8.0 Hz), 7.37 -7.34 (m, 5H), 7.01-6.96 (m, 4H), 4.62 (s, 1H), 3.31 (s, 2H), 2.95 (t, 2H, J = 6.0 Hz), 2.83-2.80 (m, 2H ), 2.71-2.66 (m, 4H), 1.86 (quintet, 2H, J = 6.0 Hz).

Example 171. 2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide (Compound Number 171)

A target compound having a yield of 32% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.47 (bs, 1H), 7.67 (d, 2H, J = 8.8 Hz), 7.59 (d, 2H, J = 8.8 Hz), 7.37 (dd, 4H, J = 8.8 Hz), 7.01 (t, 4H, J = 8.4 Hz), 4.63 (s, 1H), 3.31 (s, 2H), 2.94 (t, 2H, J = 5.6 Hz), 2.83-2.80 (m, 2H) , 2.70-2.66 (m, 4H), 1.85 (quintet, 2H, J = 6.0 Hz).

Example 172. N- (2,4-dimethylphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) Acetamide (Compound No. 172)

In the same manner as in Synthesis Example 4 Representative 2- (chloromethyl) -6-methyl-benzo [d] oxazole (61 mg, 0.34 mmol) and 2- (1,4-diazepan-1-yl) - N - 79 mg (58%) of the title compound were obtained using (2,4-dimethylphenyl) acetamide (114 mg, 0.44 mmol) and EDIPA (120 μL, 0.67 mmol).

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.20 (bs, 1H), 7.93 (d, J = 8.2 Hz, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.30 (bs, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 6.96 (s, 1H), 4.00 (s, 2H), 3.28 (s, 2H), 2.96-2.87 (m, 8H), 2.48 (s, 3H), 2.27 (s, 3H), 2.18 (s, 3H), 1.90 (quintet, J = 5.8 Hz, 2H).

Example 173. N - (3,4- dimethyl-phenyl) -2- (4 - ((6-methylbenzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) Acetamide (Compound No. 173)

The title compound was obtained in the same manner as the representative synthesis example, yield 48%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.18 (bs, 1H), 7.58 (d, J = 8.1 Hz, 1H), 7.36-7.26 (m, 3H), 7.15 (dd, J ₁ = 8.1 Hz, J ₂ = 0.9 Hz, 1H), 7.05 (d, J = 8.1 Hz, 1H), 4.04 (s, 2H), 3.28 (s, 2H), 2.98-2.88 (m, 8H), 2.49 (s, 3H), 2.22 (s, 3H), 2.19 (s, 3H), 1.92 (quintet, J = 5.7 Hz, 2H).

Example 174 N- (2,6-dimethylphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) Acetamide (Compound No. 174)

The title compound was obtained in the same manner as the representative synthesis example, with a yield of 96%.

¹ H NMR (CDCl ₃ , 300 MHz) δ 8.75 (bs, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.29 (s, 1H), 7.14-7.07 (m, 4H), 4.00 (s, 2H), 3.33 (s, 2H), 2.95-2.92 (m, 8H), 2.47 (s, 3H), 2.20 (s, 6H), 1.91 (quintet, J = 5.7 Hz, 2H).

Example 175. N- (2-Chlorophenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide (Compound No. 175)

A target compound having a yield of 53% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.99 (bs, 1H), 8.49 (dd, J ₁ = 8.3 Hz, J ₂ = 1.5 Hz, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.37 -7.03 (m, 5H), 4.04 (s, 2H), 3.32 (s, 2H), 3.02-2.89 (m, 8H), 2.50 (s, 3H), 1.96 (quintet, J = 5.8 Hz, 2H).

Example 176. N- (3-chlorophenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide (Compound No. 176)

A target compound having a yield of 69% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.35 (bs, 1H), 7.70 (t, J = 1.9 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 7.38-7.08 (m, 5H) , 4.04 (s, 2H), 3.27 (s, 2H), 2.98-2.85 (m, 8H), 2.49 (s, 3H), 1.90 (quintet, J = 5.7 Hz, 2H).

Example 177. N- (4-Chlorophenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide (Compound No. 177)

A target compound having a yield of 60% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.32 (bs, 1H), 7.59-7.47 (m, 3H), 7.32-7.15 (m, 3H), 4.04 (s, 2H), 3.26 (s, 2H), 2.98-2.85 (m, 8H), 2.49 (s, 3H), 1.90 (quintet, J = 5.7 Hz, 2H).

¹³ C NMR (CDCl ₃ , 75 MHz) δ 169.1, 163.1, 151.2, 138.8, 136.3, 135.7, 129.1, 129.0, 125.7, 120.6, 119.5, 110.9, 62.4, 56.1, 55.4, 55.2, 55.1, 54.1, 28.2, 21.8 .

Example 178. N- (2-fluorophenyl) -2- (4-(((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) Acetamide (Compound No. 178)

A target compound having a yield of 90% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.58 (bs, 1H), 8.32 (bs, 1H), 7.51 (d, J = 8.1 Hz, 1H), 7.09-6.94 (m, 4H), 3.96 (s, 2H), 3.22 (s, 2H), 2.92-2.79 (m, 8H), 1.86 (quintet, J = 5.9 Hz, 2H).

Example 179. N- (3-fluorophenyl) -2- (4-(((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) Acetamide (Compound No. 179)

The title compound was obtained in the same manner as the representative synthesis example, yield 48%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.29 (bs, 1H), 7.52-7.47 (m, 2H), 7.20-7.07 (m, 3H), 6.72-6.71 (m, 1H), 3.97 (s, 2H ), 3.20 (s, 2H), 2.94-2.73 (m, 8H), 2.41 (s, 3H), 1.83 (quintet, J = 5.9 Hz, 2H).

Example 180. N- (4-fluorophenyl) -2- (4-(((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) Acetamide (Compound No. 180)

A target compound having a yield of 87% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.25 (bs, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.51-7.47 (m, 2H), 7.31 (s, 1H), 7.14 (dd, J ₁ = 8.1 Hz, J ₂ = 0.6 Hz, 1H), 7.00-6.94 (m, 2H), 4.03 (s, 2H), 3.25 (s, 2H), 2.97-2.84 (m, 8H), 2.48 (s , 3H), 1.89 (quintet, J = 5.8 Hz, 2H).

Example 181. 2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide (Compound No. 181)

The target compound was obtained in the yield 58% by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.31 (bs, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.31-7.03 (m, 5H) , 4.02 (s, 2H), 3.30 (s, 2H), 2.97-2.89 (m, 8H), 2.48 (s, 3H), 2.23 (s, 3H), 1.92 (quintet, J = 5.7 Hz, 2H).

Example 182. 2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide (Compound No. 182)

A target compound having a yield of 67% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.20 (bs, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.41 (s, 1H), 7.32-7.30 (m, 2H), 7.16 (q, J = 7.8 Hz, 2H), 6.90 (d, J = 7.5 Hz, 1H), 4.03 (s, 2H), 3.25 (s, 2H), 2.97-2.84 (m, 8H), 2.48 (s, 3H), 2.32 (s, 3 H), 1.90 (quintet, J = 5.8 Hz, 2H).

Example 183. 2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide (Compound No. 183)

The title compound was obtained in the same manner as the representative synthesis example, yield 84%.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.17 (bs, 1H), 7.57 (dd, J ₁ = 8.1 Hz, J ₂ = 3.4 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.32 (s, 1H), 7.16-7.08 (m, 3H), 4.02 (s, 2H), 3.24 (s, 2H), 2.97-2.83 (m, 8H), 2.47 (s, 3H), 2.30 (s, 3H ), 1.89 (quintet, J = 5.8 Hz, 2H).

Example 184. N- (2-methoxyphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acet Amide (Compound No. 184)

The title compound was obtained in the same manner as the representative synthesis example, yield 94%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.81 (bs, 1H), 8.40 (dd, J ₁ = 7.9 Hz, J ₂ = 1.7 Hz, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.33 (bs, 1H), 7.16-6.85 (m, 4H), 4.03 (s, 2H), 3.82 (s, 3H), 3.28 (s, 2H), 3.01-2.85 (m, 8H), 2.49 (s, 3H ), 1.93 (quintet, J = 5.9 Hz, 2H).

Example 185. N- (3-methoxyphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acet Amide (Compound No. 185)

The title compound was obtained in the same manner as the representative synthesis example above, with a yield of 64%.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.30 (bs, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.56-7.33 (m, 2H), 7.16 (quintet, J = 8.2 Hz, 2H) , 6.99 (d, J = 0.9 Hz, 1H), 6.65 (dd, J ₁ = 8.3 Hz, J ₂ = 2.4 Hz, 1H), 4.03 (s, 2H), 3.79 (s, 3H), 3.28 (s, 2H), 2.97-2.87 (m, 8H), 2.48 (s, 3H), 1.91 (quintet, J = 5.7 Hz, 2H).

Example 186. N- (4-methoxyphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) acet Amide (Compound No. 186)

A target compound having a yield of 65% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.17 (bs, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.44 (d, J = 9.0 Hz, 2H), 7.31 (s, 1H), 7.14 (d, J = 8.0 Hz, 1H), 6.82 (d, J = 8.9 Hz, 2H), 4.02 (s, 2H), 3.77 (s, 3H), 3.24 (s, 2H), 2.96-2.83 (m, 8H), 2.47 (s, 3H), 1.89 (quintet, J = 5.7 Hz, 2H).

Example 187. 2- (4 - ((6-methylbenzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl ) Phenyl) acetamide (Compound No. 187)

A target compound having a yield of 79% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.93 (bs, 1H), 8.42 (d, J = 8.3 Hz, 1H), 7.59-7.51 (m, 3H), 7.32 (bs, 1H), 7.18-7.12 ( m, 2H), 3.99 (s, 2H), 3.28 (s, 2H), 2.96-2.86 (m, 8H), 2.47 (s, 3H), 1.90 (quintet, J = 5.8 Hz, 2H).

Example 188. 2- (4 - ((6-methylbenzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl ) Phenyl) acetamide (Compound No. 188)

A target compound having a yield of 83% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.41 (bs, 1H), 7.85 (s, 1H), 7.67 (d, J = 7.9 Hz, 1H), 7.51 (d, J = 8.1 Hz, 1H), 7.36 -7.22 (m, 3H), 7.08 (d, J = 0.8 Hz, 1H), 3.98 (s, 2H), 3.23 (s, 2H), 2.92-2.80 (m, 8H), 2.42 (s, 3H), 1.85 (quintet, J = 5.8 Hz, 2H).

Example 189. 2- (4 - ((6-methylbenzo [d] oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl ) Phenyl) acetamide (Compound No. 189)

A target compound having a yield of 55% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 400 MHz) δ 9.50 (bs, 1H), 7.65-7.50 (m, 5H), 7.32 (bs, 1H), 7.16 (d, J = 7.8 Hz, 1H), 4.05 (s, 2H), 3.29 (s, 2H), 2.99-2.86 (m, 8H), 2.48 (s, 3H), 1.91 (quintet, J = 5.8 Hz, 2H).

Example 190. N- (2,6-diethylphenyl) -2- (4-((6-methylbenzo [ d ] oxazol-2-yl) methyl) -1,4-diazepan-1-yl Acetamide (Compound No. 190)

A target compound having a yield of 49% was obtained in the same manner as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 8.76 (bs, 1H), 7.55 (d, J = 8.1 Hz, 1H), 7.29-7.11 (m, 6H), 4.01 (s, 2H), 3.25 (s, 2H), 2.97-2.92 (m, 8H), 2.56 (q, J = 7.6 Hz, 4H), 2.48 (s, 3H), 1.92 (quintet, J = 5.7 Hz, 2H), 1.17 (t, J = 7.5 Hz, 6H).

Example 191. N - (3- chloro-phenyl) -2- (4-neopentyl-1,4-diazepan-1-yl) acetamide (Compound No. 191)

Trimethylacetaldehyde (40 μL, 0.36 mmol) and N- (3-chlorophenyl) -2- (1,4-diazepan-1-yl) which are commercial reagents in 5 mL of dichloromethane in the same manner as the representative synthesis example 3 Acetamide (127 mg, 0.47 mmol), NaBH (OAc) ₃ (231 mg, 1.09 mmol) and molecular sieve were added and stirred for 20 minutes to obtain 36 mg (38%) of the title compound.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.44 (bs, 1H), 7.68 (t, 1H, J = 1.88 Hz), 7.48-7.06 (m, 3H), 3.26 (d, 2H, J = 1.02 Hz) , 2.88-2.81 (m, 8H), 2.29 (d, 2H, J = 0.94 Hz), 1.87-1.78 (m, 2H), 0.88 (s, 9H),

Example 192. N - (3- chloro-phenyl) -2- (4- (3,3-dimethylbutyl) -1,4-diazepan-1-yl) acetamide (Compound No. 192)

A target compound having a yield of 71% was obtained by the same method as the representative synthesis example.

¹ H NMR (CDCl ₃ , 300 MHz) δ 9.49 (bs, 1H), 7.70 (t, 1H, J = 1.98 Hz), 7.49-7.04 (m, 3H), 3.26 (d, 2H, J = 2.46 Hz) , 2.84-2.51 (m, 10H), 1.89-1.82 (m, 2H), 1.43-1.38 (m, 2H), 0.91 (s, 9H).

Example 193. 2- (4-(( 1H -Benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -1- (piperidin-1-yl Ethanone (Compound No. 193)

In 6 mL DMF in the same manner as in Synthesis Example 4 represents 2-chloro-piperidin-ethanone (0.508 mmol), 2- (1,4- diazepan-1-yl) - N - (1 H - benzo [d ] Imidazole) acetamide (0.390 mmol) and EDIPA (0.976 mmol) were added and stirred at 60 ° C for 12 hours to obtain the target compound (20%).

¹ H NMR (400 MHz, MeOD): δ 7.54-7.52 (m, 2H), 7.27-7.19 (m, 2H), 3.94 (s, 2H), 3.55-3.48 (m, 4H), 3.37 (s, 2H ), 2.84-2.78 (m, 8H), 1.89-1.87 (m, 2H), 1.54-1.50 (m, 6H).

Example 194. 2- (4-(( 1H -Benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -1-morphoethanone (Compound No. 194 )

A target compound having a yield of 17% was obtained in the same manner as the representative synthesis example.

¹ H NMR (300 MHz, MeOD) δ 7.55-7.51 (m, 2H), 7.24-7.19 (m, 2H), 3.93 (s, 2H), 3.69-3.54 (bm, 8H), 3.40 (s, 2H) , 2.79 (b, 8 H), 1.91-1.82 (m, 2 H).

¹³ C NMR (100 MHz, MeOD): δ 169.6, 152.8, 137.7, 122.0, 114.3, 66.4, 66.3, 59.8, 59.5, 55.3, 54.9, 54.1, 54.0, 53.9, 53.7, 45.7, 43.4, 41.9, 27.2.

Example 195. 2- (4-(( 1H -Benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -1- (4-methylpiperidine- 1-yl) ethanone (Compound No. 195)

A target compound having a yield of 50% was obtained in the same manner as the representative synthesis example.

¹ H NMR (400 MHz, MeOD): δ 8.00-7.99 (m, 2H), 7.79-7.77 (m, 2H), 4.65 (b, 1H), 4.58 (s, 2H), 3.88-3.84 (m, 1H ), 3.78 (b, 4H), 3.37 (b, 2H), 3.30-3.27 (m, 1H), 3.17 (b, 2H), 2.90 (b, 2H), 1.95-1.88 (bm, 4H), 1.56- 1.28 (m, 4 H), 1.15 (d, 3 H, J = 5.89 Hz).

Example 196. 2- (4-(( 1H -Benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -1- (2-ethylpiperidine- 1-yl) ethanone (Compound No. 196)

A target compound having a yield of 60% was obtained by the same method as the representative synthesis example.

¹ H NMR (400 MHz, MeOD): δ 7.55-7.51 (m, 2H), 7.23-7.20 (m, 2H), 4.88 (b, 1H), 4.36 (bd, 1H), 3.96 (s, 2H), 3.77 (bd, 1H), 3.58-3.52 (m, 2H), 3.02 (bd, 1H), 2.90-2.83 (m, 8H), 2.70 (b, 1H), 1.93 (bm, 2H), 1.71-1.31 ( m, 7H), 0.89 (t, 3H, J = 7.38 Hz).

Example 197. 2- (4-(( 1H -Benzo [ d ] imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -1- (4-benzylpiperidine- 1-yl) ethanone (Compound No. 197)

A target compound having a yield of 34% was obtained in the same manner as the representative synthesis example.

^{1 H NMR (400 MHz, MeOD} ): δ 7.85-7.83 (m, 2H), 7.61-7.59 (m, 2H), 7.36-7.23 (m, 5H), 4.57 (bd, 1H, J = 12.72 Hz), 4.37 (s, 2H), 3.81-3.75 (m, 2H), 3.67 (b, 4H), 3.22 (b, 2H), 3.14 (b, 1H), 2.77 (b, 2H), 2.66 (d, 2H, J = 6.94 Hz), 2.26 (b, 2H), 1.80 (b, 4H), 1.36 (b, 2H).

Example 198. N- (2-fluorophenyl) -2- (4-((4-phenyl-5-propylthiazol-2-yl) methyl) -1,4-diazepane-1-yl) acet Amide (Compound No. 198)

107 mg (58%) of the title compound was obtained in the same manner as the representative synthesis example.

¹ H NMR (400 MHz, MeOD) δ 9.70 (brs, 1H), 8.40 (t, 1H, J = 8.0 Hz), 7.58-7.02 (m, 8H), 3.99 (s, 2H), 3.32 (s, 2H ), 2.95-2.85 (m, 10H), 1.95-1.89 (m, 2H), 1.76-1.66 (m, 2H), 0.98 (t, 3H, J = 7.3 Hz).

Example 199. N- (2,6-diethylphenyl) -2- (4- (4-methylthiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide (compound Number 199)

A target compound having a yield of 83% was obtained in the same manner as the representative synthesis example.

¹ H NMR (400 MHz, MeOD): δ 8.77 (brs, 1H), 7.18-7.04 (m, 3H), 6.75 (s, 1H), 3.91 (s, 2H), 2.94-2.80 (m, 8H), 2.54 (q, 4H, J = 7.5 Hz), 2.36 (s, 23H), 1.86 (m, 2H), 1.15 (t, 6H, J = 7.5 Hz).

[Example]

On the other hand, the novel compound represented by Formula 1 according to the present invention can be formulated in various forms according to the purpose. The following is a description of some formulations containing the compound of Formula 1 according to the present invention as an active ingredient, but the present invention is not limited thereto.

Formulation 1: tablet (direct pressure)

After 5.0 mg of the active ingredient was sieved, 14.1 mg of lactose, 0.8 mg of crospovidone USNF and 0.1 mg of magnesium stearate were mixed and pressurized to make tablets.

Formulation 2: Tablet (Wet Granulation)

After 5.0 mg of the active ingredient was sieved, 16.0 mg of lactose and 4.0 mg of starch were mixed. 0.3 mg of Polysorbate 80 was dissolved in pure water, and an appropriate amount of this solution was added, followed by atomization. After drying, the granules were sieved and mixed with 2.7 mg of colloidal silicon dioxide and 2.0 mg of magnesium stearate. The granules were pressed into tablets.

Formulation 3: Powders and Capsules

5.0 mg of the active ingredient was sieved, followed by mixing with 14.8 mg of lactose, 10.0 mg of polyvinyl pyrrolidone, and 0.2 mg of magnesium stearate. The mixture was filtered through a hard No. Filled in 5 gelatin capsules.

Formulation 4: Injection

Injectables were prepared by containing 100 mg as the active ingredient, as well as 180 mg of mannitol, 26 mg of Na ₂ HPO ₄ -12H ₂ O and 2974 mg of distilled water.

[Experimental Example]

On the other hand, for the novel compound represented by the formula (1) according to the present invention was tested for the antagonism of the T-type calcium channel by the method as shown in the following experimental example. The synthesized compound was obtained by using the FDSS6000 as a method of the following experimental example to determine the percent inhibition of the T-type calcium channel.

Experimental Example: T-type calcium channel activity detection method using FDSS6000

Stable α1G T-type calcium channel and Kir2.1 using 96-well cell distributor (Titertek) in 96-well plates treated with poly-L-lysine (0.05 mg / ml) 12-24 hours before activity detection The cells of HEK293 cell line (α1G cell line: KCTC 10519BP, Genetic Bank of Korea Research Institute of Bioscience and Biotechnology), which were expressed as, were dispensed at a density of 4 × 10 ⁴ per well. On the day of the experiment, the cells attached to the 96-well plate were subjected to HEPES buffer (unit mM: 150 NaCl, 5 KCl, 1 MgCl ₂ , 2 CaCl ₂ , 10 HEPES, 10) using a 96-well plate auto washing machine (Bio Tek). After washing three times with glucose, pH 7.4) and reacting for 1 hour at room temperature in HEPES buffer solution containing 5 μM Fluoro-3 / AM and 0.001% Pluronic F-127, it was labeled with fluorescent dye. Washed again with HEPES buffer twice. It was then washed once with HEPES buffer containing 10 mM CaCl ₂ and adjusted to a final volume of 81 μL 10 minutes before measuring the FDSS6000 instrument. Apart from the 96-well plates in which the cells were prepared, two 96-well drug plates were prepared to contain KCl (final concentration 75 mM) and blocker drug to activate T-type calcium channels. Since most cell-based HTS instruments have a liquid application system for drug injection but no liquid inhalation system, 27 μL of blocking drug and KCl in 10 mM CaCl ₂ HEPES buffer at 5 times higher concentration are prepared. Diluted by 1/5 in 135 μL, the final volume of the plate, is measured. Specific FDSS6000 measurement conditions were to measure the change in intracellular calcium concentration changed by KCl administration after 75 seconds of drug pretreatment after recording 20 seconds of reference value. It was set at 100% and the percentage (%) inhibitory effect on the inhibitory effect of the test substance was obtained, and 10 μM of mibepradil was always used as a control drug.

As a detailed calcium imaging technique, the excitation wavelengths (340 nm and 380 nm) were selectively exposed to cells by a computer-controlled filter wheel in view of four light sources of xenon lamps mounted on the FDSS6000. Data were obtained every 1.23 seconds, and the emitter fluorescence light entering through a 515 nm long-pass filter was passed through a cooling CCD camera built into the instrument and then 96-well by a digital fluorescence analyzer. Average values of 340/380 were obtained for each well in the phase. All image data and analysis was done using the FDSS6000 dedicated program provided by Hamamatsu Photonics.

The% inhibition rate of calcium migration of T-type calcium channels of the novel compounds according to the present invention is shown in Table 1 below.

Test compound % Inhibition of FDSS (10 μM) Test compound % Inhibition of FDSS (10 μM) Compound number 1 41.0 Compound number 132 61.06 Compound number 39 57.40 Compound number 133 56.82 Compound number 40 47.64 Compound number 134 56.0 Compound number 41 56.22 Compound number 135 50.8 Compound number 44 46.35 Compound number 136 60.11 Compound number 45 46.64 Compound number 138 52.08 Compound number 46 56.29 Compound number 139 63.71 Compound number 47 41.66 Compound number 140 66.15 Compound number 48 51.29 Compound number 141 66.51 Compound number 49 51.83 Compound number 142 61.72 Compound number 50 54.79 Compound number 143 64.25 Compound number 51 44.75 Compound 144 41.68 Compound number 52 59.15 Compound number 145 60.72 Compound number 53 46.07 Compound number 146 50.92 Compound number 54 32.36 Compound number 147 41.77 Compound number 55 41.68 Compound number 148 59.17 Compound number 56 60.07 Compound No. 149 49.50 Compound number 57 60.73 Compound number 150 51.91 Compound number 58 56.12 Compound 151 69.16 Compound number 61 64.36 Compound number 152 73.93 Compound number 65 58.76 Compound number 153 65.83 Compound number 66 55.65 Compound No. 156 55.36 Compound number 67 61.17 Compound number 162 41.49 Compound number 68 44.36 Compound number 163 49.30 Compound number 70 44.24 Compound No. 164 33.62 Compound number 71 72.08 Compound number 168 44.27 Compound number 72 76.72 Compound number 172 56.01 Compound number 73 75.77 Compound number 173 70.83 Compound number 74 72.93 Compound number 174 47.20 Compound number 98 43.89 Compound number 175 47.54 Compound number 101 36.92 Compound number 176 51.99 Compound number 102 35.93 Compound number 177 59.99 Compound number 113 50.62 Compound number 178 48.02 Compound number 114 41.91 Compound number 179 61.38 Compound number 115 71.96 Compound number 180 62.20 Compound number 116 41.26 Compound number 181 46.98 Compound number 117 62.66 Compound number 182 78.92 Compound 118 40.55 Compound number 183 63.66 Compound 119 35.95 Compound number 184 47.54 Compound number 120 53.43 Compound number 185 41.90 Compound number 121 60.12 Compound number 186 46.25 Compound number 122 48.87 Compound number 188 74.86 Compound number 123 56.33 Compound number 190 66.71 Compound number 124 52.84 Compound number 191 43.48 Compound number 125 33.56 Compound number 192 59.94 Compound number 126 60.01 Compound number 197 52.51 Compound number 127 57.27 Compound number 198 60.16 Compound number 128 42.15 Compound number 199 40.44 Compound number 129 49.78 Mibepradil 79.29 Compound number 130 44.79

 Since the novel 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound represented by Chemical Formula 1 has an antagonistic action on T-type calcium channels, brain diseases such as epilepsy and hypertension It can be usefully used as a preventive or therapeutic agent for pain diseases such as heart disease such as angina pectoris, chronic pain, neuropathic pain, or cancer-related diseases.

Claims (8)

A compound according to claim 1, which is a 2- (4-substituted-1,4-diazepan-1-yl) acetamide compound or a pharmaceutically acceptable salt thereof.
[Formula 1]

In Chemical Formula 1,
n is 0, 1, 2, or 3;
R ¹ is a C ₁ to C ₆ alkyl group in which 1 to 3 substituents selected from phenyl and halophenyl are substituted or unsubstituted; Oxazolyl group; Thiazolyl group; Or an imidazolyl group, wherein an oxazolyl group, thiazolyl group, or imidazolyl group may be substituted or unsubstituted with 1 to 3 substituents selected from halo, C ₁ -C ₆ alkyl, and phenyl,
R ² and R ³ are the same as or different from each other and are a hydrogen atom; Or 1 to 3 substituents selected from halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ haloalkyl are substituted or unsubstituted phenyl groups; Or R ² and R ³ represent a heterocycloalkyl group selected from a piperidinyl group, a piperazinyl group, and a morpholinyl group formed by bonding to each other with the nitrogen atom to which they are bonded, wherein the heterocycloalkyl group is halo, C ₁ -C One to three substituents selected from ₆ alkyl, and phenyl may be substituted or unsubstituted.
The method according to claim 1,
The oxazolyl group, thiazolyl group, or imidazolyl group may be each selected from 1 to 3 selected from fluoro, chloro, methyl, ethyl, n -propyl, isopropyl, n -butyl, isobutyl, tert -butyl, and phenyl. Compounds, characterized in that the substituent is substituted or unsubstituted.
The method according to claim 1,
Wherein the heterocycloalkyl group is substituted or unsubstituted with 1 to 3 substituents selected from fluoro, chloro, methyl, ethyl, n -propyl, isopropyl, n -butyl, isobutyl, tert -butyl, phenyl, and benzyl Characterized by a compound.
The method according to claim 1,
N is 0, or 1;
R ¹ is isopropyl group, tert -butyl group, (4-fluorophenyl) methyl group, diphenylmethyl group, di (4-fluorophenyl) methyl group, thiazol-2-yl group, 4-methylthiazole-2 -Yl group, 4-phenyl-5-propylthiazol-2-yl group, 1H -imidazol-2-yl group, 2-phenyl- 1H -imidazol-2-yl group, oxazol-2-yl group, 4- A phenyl-5-propyloxazol-2-yl group or a 4,5-dimethyloxazol-2-yl group;
R ² and R ³ are the same as or different from each other and are a hydrogen atom, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2- Methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2,3-dimethylphenyl group, 2,4-dimethylphenyl group, 2,5-dimethylphenyl group, 2,6-dimethylphenyl group, 3,4-dimethylphenyl group, 2, 3-diethylphenyl group, 2,4-diethylphenyl group, 2,5-diethylphenyl group, 2,6-diethylphenyl group, 3,4-diethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2- (trifluoromethyl) phenyl group, 3- (trifluoromethyl) phenyl group, or 4- (trifluoromethyl) phenyl group, or R ² and R ³ to which they are bonded Piperidinyl, 4-methylpiperidinyl, 2-ethylpiperidinyl, 4-benzylpiperidinyl, piperazinyl, 4-methylpiperazinyl, or morpholino groups formed by bonding to nitrogen atoms together To me Compound, characterized in that that.
The method according to claim 1,
N- (2,6-diethylphenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
N- (2,4-dimethylphenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
N- (3,4-dimethylphenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
N- (2,6-dimethylphenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
N- (2-chlorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
N- (3-chlorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
N- (4-chlorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
N- (2-fluorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
N- (3-fluorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
N- (4-fluorophenyl) -2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) -N - o -tolylacetamide;
2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) -N - m -tolylacetamide;
2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) -N - p -tolylacetamide;
N- (2-methoxyphenyl) -2- (4-thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
N- (3-methoxyphenyl) -2- (4-thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
N- (4-methoxyphenyl) -2- (4-thiazol-2-ylmethyl) -1,4-diazepan-1-yl) acetamide;
2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide;
2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide;
2- (4- (thiazol-2-ylmethyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide;
N- (2,6-diethylphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2,6-dimethylphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (3,4-dimethylphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2,4-dimethylphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2-chlorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (3-chlorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (4-chlorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2-fluorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (3-fluorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (4-fluorophenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide;
2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide;
2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide;
N- (2-methoxyphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (3-methoxyphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (4-methoxyphenyl) -2- (4-((4-phenyl-5-propyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
2- (4 - ((4-phenyl-5-propyl-oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide Amide;
2- (4 - ((4-phenyl-5-propyl-oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide Amide;
2- (4 - ((4-phenyl-5-propyl-oxazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide Amide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (2,6- diethyl-phenyl) acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2,4- dimethyl-phenyl) -acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3,4- dimethyl-phenyl) -acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2,6- dimethyl-phenyl) -acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- chlorophenyl) acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- chlorophenyl) acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- chlorophenyl) acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (2-fluorophenyl) acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (3-fluorophenyl) acetamide;
2- (4 - ((1 H - il-imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (4-fluorophenyl) acetamide;
2- (4-(( 1H -imidazol-2-yl) methyl) -1,4-diazepan-1-yl) -N - o -tolylacetamide;
2- (4-(( 1H -imidazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide;
2- (4-(( 1H -imidazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (2- methoxyphenyl) acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (3- methoxyphenyl) acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - (4- methoxyphenyl) acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepane -1-) - N - methyl (2- (trifluoromethyl) phenyl acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide;
2- (4 - ((1 H - imidazol-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide;
N- (2,6-diethylphenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2,4-dimethylphenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (3,4-dimethylphenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2,6-dimethylphenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2-chlorophenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide;
N- (3-chlorophenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide;
N- (4-chlorophenyl) -2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) acetamide;
2- (4 - ((4,5-Dimethyl-2-yl) methyl) diazepan-1-yl) - N - (2-fluorophenyl) acetamide;
2- (4 - ((4,5-Dimethyl-2-yl) methyl) diazepan-1-yl) - N - (3-fluorophenyl) acetamide;
2- (4 - ((4,5-Dimethyl-2-yl) methyl) diazepan-1-yl) - N - (4-fluorophenyl) acetamide;
2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide;
2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide;
2- (4-((4,5-dimethyloxazol-2-yl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide;
2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2-methoxyphenyl) acetamide;
2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide;
2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- methoxyphenyl) acetamide;
2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide;
2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide;
2- (4 - ((4,5-Dimethyl-2-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide;
N- (2,6-diethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2,4-dimethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (3,4-dimethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2,6-dimethylphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2-chlorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (3-chlorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (4-chlorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2-fluorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (3-fluorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (4-fluorophenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) -N - o -tolylacetamide;
2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) -N - m -tolylacetamide;
2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) -N - p -tolylacetamide;
N- (2-methoxyphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-azpan-1-yl) acetamide;
N- (3-methoxyphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (4-methoxyphenyl) -2- (4-((2-phenyl-1 H -imidazol-5-yl) methyl) -1,4-diazepan-1-yl) acetamide;
2- (4 - ((2-phenyl -1 H-imidazol-5-yl) methyl) -1,4-diazepan-1-yl) - N-acetamido (methyl) phenyl-2- (trifluoromethyl) Amide;
2- (4 - ((2-phenyl -1 H-imidazol-5-yl) methyl) -1,4-diazepan-1-yl) - N-acetamido (methyl) phenyl 3- (trifluoromethyl) Amide;
2- (4 - ((2-phenyl -1 H-imidazol-5-yl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide Amide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2,6- diethyl-phenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2,4- dimethyl-phenyl) -acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (3,4- dimethyl-phenyl) -acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2,6- dimethyl-phenyl) -acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2-chlorophenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (3- chlorophenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (4-chlorophenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2-fluorophenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (3-fluorophenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (4-fluorophenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepane-1-yl) -N - o -tolylacetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepane-1-yl) -N - m -tolylacetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepane-1-yl) -N - p -tolylacetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2-methoxyphenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (3- methoxyphenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (4-methoxyphenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (2- (trifluoromethyl) phenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (3- (trifluoromethyl) phenyl) acetamide;
2- (4- (bis (4-fluorophenyl) methyl) -1,4-diazepan-1-yl) - N - (4- (trifluoromethyl) phenyl) acetamide;
N- (3-chlorophenyl) -2- (4-neopentyl-1,4-diazepan-1-yl) acetamide;
N- (3-chlorophenyl) -2- (4- (3,3-dimethylbutyl) -1,4-diazepan-1-yl) acetamide;
N- (2-fluorophenyl) -2- (4-((4-phenyl-5-propylthiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide;
N- (2,6-diethylphenyl) -2- (4- (4-methylthiazol-2-yl) methyl) -1,4-diazepan-1-yl) acetamide; And
Compound selected from pharmaceutically acceptable salts thereof.
The pharmaceutical composition for the treatment and prevention of diseases selected from epilepsy, hypertension, angina pectoris, chronic pain, neurological pain, and cancer, wherein the compound of any one selected from claims 1 to 5 is included as an active ingredient.
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