NOVEL QUINOLINE COMPOUND AND USE THEREOF

Abstract

The present invention relates to a novel quinoline compound and a use thereof and to a novel quinoline compound exhibiting CYP4A inhibition activity and a use thereof for preventing, alleviating, treating a metabolic disease. The compound disclosed in the present invention has a remarkable effect of inhibiting CYP4A and exhibits the activities of promoting the absorption of glucose into hepatocytes, inhibiting fat accumulation in hepatocytes, suppressing endoplasmic reticulum-induced reactive oxygen species, and treating steatohepatitis, and thus can be very advantageously used for developing therapeutics for metabolic diseases such as diabetes mellitus and fatty liver.

Claims

1. A quinolone compound represented by the following Formula (I), a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate or a salt thereof: ##STR00173## wherein R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, halo, haloalkane, hydroxy, carboxyl, carbonyl, amino, amide, cyano, nitro, alkyl, alkenyl, alkynyl and alkoxy, wherein R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are each independently selected from the group consisting of hydrogen, halo, haloalkane, hydroxy, carboxyl, carbonyl, amino, amide, sulfonyl, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, phenoxy, substituted or unsubstituted phenyl, and substituted or unsubstituted heteroaryl.

2. The quinolone compound, a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate or a salt thereof according to claim 1, wherein R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, halo, C1-C6 haloalkane, hydroxy, substituted or unsubstituted C1-C6 carboxyl, substituted or unsubstituted C1-C6 carbonyl, substituted or unsubstituted amino, substituted or unsubstituted C1-C6 amide, cyano, substituted or unsubstituted nitro, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C1-C10 alkenyl, substituted or unsubstituted C1-C10 alkynyl and substituted or unsubstituted C1-C10 alkoxy.

3. The quinolone compound, a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate or a salt thereof according to claim 1, wherein R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen; halo; substituted or unsubstituted linear or branched C1-C6 alkyl; C1-C6 haloalkane; and substituted or unsubstituted linear or branched C1-C6 alkoxy.

4. The quinolone compound, a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate or a salt thereof according to claim 1, wherein R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, halo, trifluoromethyl, unsubstituted linear C1-C6 alkyl and unsubstituted linear C1-C6 alkoxy.

5. The quinolone compound, a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate or a salt thereof according to claim 1, wherein R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are each independently selected from the group consisting of hydrogen; halo; C1-C6 haloalkane; hydroxy; substituted or unsubstituted C1-C6 carboxyl; substituted or unsubstituted C1-C6 carbonyl; substituted or unsubstituted amino; substituted or unsubstituted C1-C6 amides; sulfonyl; cyano; nitro; substituted or unsubstituted C1-C6 alkyl; substituted or unsubstituted C1-C6 alkenyl; substituted or unsubstituted C1-C6 alkynyl; substituted or unsubstituted C1-C6 alkoxy; substituted or unsubstituted C6-C10 phenoxy; substituted or unsubstituted C6-C10 phenyl; and substituted or unsubstituted C3-C10 heteroaryl.

6. The quinolone compound, a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate or a salt thereof according to claim 1, wherein R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are each independently selected from the group consisting of hydrogen; halo; trifluoromethyl; hydroxy; carboxyl; C1-C6 alkylcarbonyl; C1-C6 alkoxycarbonyl; dimethylaminocarbonyl; amino; dimethylamino; diethylamino; methylcarbonylamino; sulfonyl; cyano; nitro; unsubstituted linear C1-C6 alkyl; unsubstituted linear C1-C6 alkoxy; substituted or unsubstituted C6-C10 phenoxy; substituted or unsubstituted C6-C10 phenyl; substituted or unsubstituted C5-C10 pyridine; and substituted or unsubstituted C4-C10 pyrimidines.

7. The quinolone compound, a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate or a salt thereof according to claim 1, wherein the compound is selected from the group consisting of (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-(phenylsulfonyl)piperidin-3-yl)methanone, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-tosylpiperidin-3-yl)methanone, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((4-fluorophenyl)sulfonyl)piperidin-3-yl)methanone, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((4-(dimethylamino)phenyl)sulfonyl)piperidin-3-yl)methanone, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((4-hydroxyphenyl)sulfonyl)piperidin-3-yl)methanone, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((3-nitrophenyl)sulfonyl)piperidin-3-yl)methanone, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((4-(trifluoromethyl)phenyl)sulfonyl)piperidin-3-yl)methanone, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((3-fluorophenyl)sulfonyl)piperidin-3-yl)methanone, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((4-phenoxyphenyl)sulfonyl)piperidin-3-yl)methanone, 4-(3-(1-7-chloroquinolin-4-yl) piperazine-4-carbonyl) piperidin-1-ylsulfonyl) benzonitrile, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-(4-methylsulfonyl)phenylsulfonyl)piperidin-3-yl)methanone, methyl 4-(3-(1-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidin-1-yl)sulfonyl)benzoate, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-(4-phenylbenzenesulfonyl)piperidin-3-yl)methanone, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-(3-methoxyphenylsulfonyl)piperidin-3-yl)methanone, N-(4-((3-(4-(2-methylquinolin-4-yl)piperazin-1-carbonyl)piperidin-1-yl)sulfonyl)phenyl)acetamide, (R)—N-(4-((3-(4-(2-methylquinolin-4-yl)piperazin-1-carbonyl)piperidin-1-yl)sulfonyl)phenyl)acetamide, (S)—N-(4-((3-(4-(2-methylquinolin-4-yl)piperazin-1-carbonyl)piperidin-1-yl)sulfonyl)phenyl)acetamide, (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-((4-nitrophenyl)sulfonyl)piperidin-3-yl)methanone, (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(phenylsulfonyl)piperidin-3-yl)methanone, (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-tosylpiperidin-3-yl)methanone, (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(m-tosylsulfonyl)piperidin-3-yl)methanone, (1-((3,4-dimethylphenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (1-(4-ethylphenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (1-((4-fluorophenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (1-((4-chlorophenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (4-2-methylquinolin-4-yl)piperazin-1-yl)(1-(4-(trifluorophenyl)phenylsulfonyl)piperidin-3-yl)methanone, (1-(3-fluorophenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(3-nitrophenylsulfonyl)piperidin-3-yl)methanone, (1-(4-methoxyphenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(pearlfluorophenylsulfonyl)piperidin-3-yl)methanone, (1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (1-(4-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (1-(2-fluorophenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(4-phenoxyphenylsulfonyl)piperidin-3-yl)methanone, 4-(3-1-(2-methylquinolin-4-yl)piperazin-4-carbonyl)piperidin-1-ylsulfonyl)benzonitrile, (4-(2-methylquinolin-4-yl)pyrazin-1-yl)(1-(4-(methylsulfonyl)phenylsulfonyl)piperidin-3-yl)methanone, methyl 4-(3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)benzoate, (4-(2-methylquinolin-4-yl)pyrazin-1-yl)(1-(4-phenylbenzenesulfonyl)piperidin-3-yl)methanone, (1-(3-methoxyphenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (1-((4-bromophenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(phenylsulfonyl)piperidin-3-yl)methanone, (1-((4-fluorophenyl)sulfonyl)piperidin-3-yl)(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-((4-hydroxyphenyl)sulfonyl)piperidin-3-yl)methanone, (1-((4-(dimethylamino)phenyl)sulfonyl)piperidin-3-yl)(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)methanone, N-(4-(3-(1-(7-fluoroquinolin-4-yl)piperazine-4-carbonyl))piperidin-1-ylsulfonyl)phenyl)acetamide, (R)—N-(4-(3-(1-(7-fluoroquinolin-4-yl)piperazin-4-carbonyl))piperidin-1-ylsulfonyl)phenyl)acetamide, (S)—N-(4-(3-(1-(7-fluoroquinolin-4-yl)piperazin-4-carbonyl))piperidin-1-ylsulfonyl)phenyl)acetamide, (R)-(1-((4-(dimethylamino)phenyl)sulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (S)-(1-((4-(dimethylamino)phenyl)sulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-nitrophenylsulfonyl)piperidin-3-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-nitrophenylsulfonyl)piperidin-3-yl)methanone, (1-(4-(diethylamino)phenyl)sulfonyl)piperidin-3-yl)(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-methoxyphenylsulfonyl)piperidin-3-yl)methanone, 1-(4-(3-(1-fluoroquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)phenyl)ethanone, (4-(7-fluoroquinolin-4-yl)pyrazin-1-yl)(1-(4-phenylbenzenesulfonyl)piperidin-3-yl)methanone, (1-(4-bromophenylsulfonyl)piperidin-3-yl)(4-7-fluoroquinolin-4-yl)piperazin-1-yl)methanone, (R)-(1-(4-bromophenylsulfonyl)piperidin-3-yl)(4-7-fluoroquinolin-4-yl)piperazin-1-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-methoxyphenylsulfonyl)piperidin-3-yl)methanone, (R)—N-(3-(3-(1-(7-fluoroquinolin-4-yl)piperazin-4-carbonyl))piperidin-1-ylsulfonyl)phenyl)acetamide, (R)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-nitrophenylsulfonyl)piperidin-3-yl)methanone, (R)-(1-((3-(dimethylamino)phenyl)sulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (1-(3-bromophenylsulfonyl)piperidin-3-yl)(4-7-fluoroquinolin-4-yl)piperazin-1-yl)methanone, N-(4-(3-(1-(2-(trifluoromethyl)quinolin-4-yl)piperazin-4-carbonyl)piperidin-1-ylsulfonyl)phenyl)acetamide, (1-(phenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, (1-tosylpiperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, (1-(4-fluorophenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, (1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, (1-(4-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, (R)-(1-(4-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, (S)-(1-(4-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, (1-(4-(trifluoromethyl)phenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, (1-(3-fluorophenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, (1-(pearlfluorophenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, (1-(phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (1-(4-fluorophenyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (1-((4-hydroxyphenyl)sulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, N-(4-((3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidin-1-yl)sulfonyl)phenyl)acetamide, (R)-(1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (S)-(1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (1-(4-nitrophenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (1-(3-nitrophenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (1-(4-(diethylamino)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (4-(quinolin-4-yl)pyrazin-1-yl)(1-(4-phenylbenzenesulfonyl)piperidin-3-yl)methanone, (1-(4-bromophenylphenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (1-(3-Methoxyphenylphenylsulfonyl)piperidine-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, N-(4-(3-(1-(7-methoxyquinolin-4-yl)piperazin-4-carbonyl))piperidin-1-ylsulfonyl)phenyl)acetamide, (4-(7-methoxyquinolin-4-yl)piperazin-1-yl)(1-tosylpiperidin-3-yl)methanone, (1-(4-fluorophenyl)sulfonyl)piperidin-3-yl)(4-(7-methoxyquinolin-4-yl)piperazin-1-yl)methanone, (1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(7-methoxyquinolin-4-yl)piperazin-1-yl)methanone, (1-(4-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(7-methoxyquinolin-4-yl)piperazin-1-yl)methanone, (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-(3-hydroxyphenylsulfonyl)piperidin-3-yl)methanone, (1-(3-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (4-(7-fluoroquinolin-4-yl)(1-(3-hydroxyphenylsulfonyl)piperidin-3-yl)methanone, (1-(3-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (1-((4-aminophenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, (1-((4-aminophenyl)sulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, 4-(3-(1-(7-chloroquinolin-4-yl)piperazin-1-carbonyl)piperidin-1-yl)sulfonyl)benzoic acid, 4-(3-(1-7-chloroquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)-N,N-dimethylbenzamide, 4-(3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)benzoic acid, N,N-dimethyl-4-(3-(1-(2-methylquinolin-4-yl)piperazin-4-carbonyl)piperidin-1-ylsulfonyl)benzamide, (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-((4-(pyridin-4-yl)phenyl)sulfonyl)piperidin-3-yl)methanone, (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-((4-(pyrimidin-5-yl)phenyl)sulfonyl)piperidin-3-yl)methanone, (1-((4-(2-methylpyrimidin-5-yl)phenyl)sulfonyl)piperidin-4-yl)(4-(2-methylquinolin-4-yl)phenyl)piperazin-1-yl)methanone, (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-((4-(pyridin-3-yl)phenyl)sulfonyl)piperidin-3-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-(pyridin-4-)phenylsulfonyl)piperidin-3-yl)methanone, (R)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-(pyridin-4-yl)phenylsulfonyl)piperidin-3-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-(pyridin-3-)phenylsulfonyl)piperidin-3-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-(pyridin-4-yl)phenylsulfonyl)piperidin-3-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-(pyridin-3-yl)phenylsulfonyl)piperidin-3-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-(pyrimidine-5-)phenylsulfonyl)piperidin-3-yl)methanone, (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-(pyrimidine-5-)phenylsulfonyl)piperidin-3-yl)methanone, (1-(4-(pyridin-4-yl)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (1-(4-(pyridin-3-yl)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, (1-(4-(2-methylpyrimidin-5-yl)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone, N-(4-((3-(4-(7-chloroquinolin-4-yl)piperazin-1-carbonyl)piperidin-1-yl)sulfonyl)phenyl)acetamide and (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((4-nitrophenyl)sulfonyl)-piperidin-3-yl)methanone.

8. The quinolone compound, a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate or a salt thereof according to claim 1, wherein the quinolone compound, a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate or a salt thereof inhibits CYP4A.

9. A method for preparing the compound according to claim 1, comprising (a) reacting a compound of Formula (i) with piperidine to prepare a compound of Formula (ii), and reacting a compound of Formula (ii) with a compound of Formula (iii) to prepare a compound of Formula (iv); and (b) reacting a compound of Formula (iv) with trifluoroacetic acid (TFA) to prepare a compound of Formula (v) and reacting it with Formula (vi), ##STR00174## ##STR00175## in the above Formula, R.sup.1 to R.sup.7 are as defined in claim 1 above.

10. A pharmaceutical composition for preventing or treating a metabolic disease comprising a quinolone compound represented by the following Formula (I), a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate, or a pharmaceutically acceptable salt thereof as an active ingredient: ##STR00176## wherein R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, halo, haloalkane, hydroxy, carboxyl, carbonyl, amino, amide, cyano, nitro, alkyl, alkenyl, alkynyl and alkoxy, wherein R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are each independently selected from the group consisting of hydrogen, halo, haloalkane, hydroxy, carboxyl, carbonyl, amino, amide, sulfonyl, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, phenoxy, substituted or unsubstituted phenyl, and substituted or unsubstituted heteroaryl.

11. The pharmaceutical composition according to claim 10, wherein the metabolic disease is diabetes or fatty liver disease.

12. The pharmaceutical composition according to claim 10, wherein the diabetes is type 2 diabetes.

13. The pharmaceutical composition according to claim 10, wherein the diabetes is derived from obesity.

14. The pharmaceutical composition according to claim 10, wherein the fatty liver disease is selected from the group consisting of fatty liver, steatohepatitis, and fatty liver-associated cirrhosis.

15. A food composition for preventing or improving metabolic diseases comprising a quinolone compound represented by the following Formula (I), a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate, or a salt thereof as an active ingredient: ##STR00177## wherein R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, halo, haloalkane, hydroxy, carboxyl, carbonyl, amino, amide, cyano, nitro, alkyl, alkenyl, alkynyl and alkoxy, wherein R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are each independently selected from the group consisting of hydrogen, halo, haloalkane, hydroxy, carboxyl, carbonyl, amino, amide, sulfonyl, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, phenoxy, substituted or unsubstituted phenyl, and substituted or unsubstituted heteroaryl.

16. Use of a quinolone compound represented by the following Formula (I), a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate, or a pharmaceutically acceptable salt thereof for preparing an agent for the prevention or treatment of metabolic diseases: ##STR00178## wherein R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, halo, haloalkane, hydroxy, carboxyl, carbonyl, amino, amide, cyano, nitro, alkyl, alkenyl, alkynyl and alkoxy, wherein R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are each independently selected from the group consisting of hydrogen, halo, haloalkane, hydroxy, carboxyl, carbonyl, amino, amide, sulfonyl, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, phenoxy, substituted or unsubstituted phenyl, and substituted or unsubstituted heteroaryl.

17. A method of treating a metabolic disease comprising administering to a subject in need thereof an effective amount of a composition comprising a quinolone compound represented by the following Formula (I), a racemic compound, a diastereomer, a geometric isomer, a stereoisomer, a hydrate, or a pharmaceutically acceptable salt thereof as an active ingredient: ##STR00179## wherein R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, halo, haloalkane, hydroxy, carboxyl, carbonyl, amino, amide, cyano, nitro, alkyl, alkenyl, alkynyl and alkoxy, wherein R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are each independently selected from the group consisting of hydrogen, halo, haloalkane, hydroxy, carboxyl, carbonyl, amino, amide, sulfonyl, cyano, nitro, alkyl, alkenyl, alkynyl, alkoxy, phenoxy, substituted or unsubstituted phenyl, and substituted or unsubstituted heteroaryl.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0264] FIG. 1 shows the results of the compound of the present invention promoting glucose uptake in liver cells treated with thapsigargin to induce endoplasmic reticulum stress.

[0265] FIG. 2 shows the results of the compound of the present invention inhibiting the accumulation of fat in the liver cells treated with thapsigargin to induce endoplasmic reticulum stress.

[0266] FIG. 3 shows the results of removal of active oxygen from the compound of the present invention in liver cells subjected to endoplasmic reticulum stress by treatment with thapsigargin.

MODE FOR CARRYING OUT INVENTION

[0267] Hereinafter, the present invention will be described in detail.

[0268] However, the following examples are only illustrative of the present invention, and the content of the present invention is not limited to the following examples.

[0269] The present inventors confirmed the compound using the following analytical equipment to confirm the synthesized compound.

[0270] For NMR (Nuclear Magnetic Resonance), a Bruker Avance III 400 MHz spectrometer, Bruker Avance Neo 400 MHz spectrometer, or A ZKNJ BIXI-1 300 MHz spectrometer was used. Agilent 1260 series LC/Mass system or Waters Acquity UPLC system with diode-array detector (DAD) or photo-diode array detector (PDA) was used to confirm the molecular weight of the compound, and molecular weight was measured through a mass detector composed of an electrospray ionization source. In addition, chiral HPLC was used to measure the e.e (enantiomeric excess) of chiral compounds, and the instrument used at this time was an Agilent 1200 series or Waters-TharSFC, and the column used was a chiralpak or chiralcel column.

Example 1: Synthesis of Quinoline-Based Precursor (Intermediate) Material

[0271] In the present invention, the following precursor preparation method was synthesized by the synthesis method of Reaction Formula 1-1 and Reaction Formula 2 below.

(1) Synthesis of (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone (Intermediate 1)

(1-1) Synthesis of 7-chloro-4-(piperazin-1-yl) quinoline

7-chloro-4-(piperazin-1-yl)quinoline

[0272] ##STR00014##

[0273] According to Reaction Formula 1, 4,7-dichloroquinoline (5.0 g, 25.25 mmol) and piperazine (10.0 g, 116 mmole) were added to ethanol (250 ml) and stirred under reflux for 12 hours. After cooling the mixture to room temperature, a saturated aqueous sodium hydrocarbon solution (sat. NaHCO.sub.3, 100 ml) was added, and dichloromethane (DCM, dichloromethane, 60 ml×3) was added and extracted to separate the organic layer, and the organic layer was removed from water using Na.sub.2SO.sub.4 (sodium bicarbonate, sodium hydrogen carbonate), filtered, and then concentrated under reduced pressure. Purification by silica gel column chromatography using dichloromethane and methanol (MeOH, 1-10%) as a developing solvent was used to obtain the target compound 7-chloro-4-(piperazin-1-yl)quinoline (Intermediate 1-1, 4, 94 g) were obtained as a white solid.

[0274] White solid (80%), .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.72 (d, J=5.0 Hz, 1H), 8.04 (d, J=2.0 Hz, 1H), 7.96 (d, J=9.0 Hz, 1H), 7.42 (dd, J=9.0, 2.1 Hz, 1H), 6.84 (d, J=5.0 Hz, 1H), 3.49 (s, 1H), 3.18 (m, 8H).

(1-2) Synthesis of tert-butyl 3-(4-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

tert-butyl 3-(4-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

[0275] ##STR00015##

[0276] After dissolving 1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (2.33 g, 10.2 mmol) and N,N-diisopropylethylamine (DIEA) (3.28 g, 25.4 mmol) in dimethylformamide (DMF, 30 ml), 1-[Bis (dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) (4.83 g, 12.7 mmol) was added and stirred at room temperature for 20 minutes, 7-Chloro-4-(piperazin-1-yl)quinoline (2.10 g, 8.47 mmol) was added, and the reaction solution was stirred at room temperature for 2 hours. After adding water (150 ml) to the reaction solution, extraction was performed using ethyl acetate (EtOAc) (30 ml×3) to separate the organic layer, the organic layer was removed from water using Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure. The compound was purified using silica gel chromatography to obtain the target compound, Intermediate 1-2 (3.87 g) as a yellow solid.

[0277] 1H MNR: (300 MHz, CDCl.sub.3): δ 8.75 (d, J=4.8 Hz, 1H), 8.07 (d, J=1.8 Hz, 1H), 7.96 (d, J=9.0 Hz, 1H), 7.47 (dd, J=9.0, 1.8 Hz, 1H), 6.85 (d, J=4.8 Hz, 1H), 4.25-4.06 (m, 2H), 3.90-3.79 (m, 4H), 3.26-3.20 (m, 4H), 2.96-2.68 (m, 4H), 1.95-1.91 (m, 1H), 1.81-1.73 (m, 2H), 1.47 (s, 9H).

(1-3) Synthesis of (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

[0278] ##STR00016##

[0279] Tert-butyl 3-(4-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate (Intermediate 1-2, 2.00 g, 4.36 mmol) was dissolved in dichloromethane (10 ml), followed by trifluoroacetic acid (TFA) (4 ml) was added and stirred at 30° C. for 1 hour. After concentrating the reaction solution, it is diluted in dichloromethane (10 ml), and after adding a saturated aqueous sodium hydrogen carbonate solution (20 ml), it is extracted three times using a dichloromethane:methanol=10:1 mixed solvent (20 ml). The organic layer was dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to obtain a yellow solid, and then recrystallized using ethyl acetate (EtOAc) and n-hexane(n-hexane) to obtain the target compound, Intermediate 1-3 (1.55 g) as a yellow solid.

[0280] 1H MNR: (400 MHz, CDCl.sub.3): δ 8.76 (d, J=5.2 Hz, 1H), 8.07 (d, J=2.4 Hz, 1H), 7.95 (d, J=9.2 Hz, 1H), 7.47 (dd, J=9.6, 2.4 Hz, 1H), 6.85 (d, J=4.8 Hz, 1H), 3.90-3.82 (m, 4H), 3.49-3.41 (br s, 1H), 3.22-3.13 (m, 6H), 3.07-3.02 (m, 1H), 2.99-2.94 (m, 1H), 2.85-2.79 (m, 1H), 1.96-1.92 (m, 1H), 1.85-1.69 (m, 3H). LC-MS (ESI): m/z 359.3 [M+H].sup.+; Purity: 100% @254 nm, 100% @214 nm.

(2) Synthesis of (4-(2-methylquinolin-4-yl)pyrazin-1-yl)(piperidin-3-yl)methanone (Intermediate 2)

(2-1) Synthesis of 2-methyl-4-(piperazin-1-yl) quinoline

2-methyl-4-(piperazin-1-yl)quinoline

[0281] ##STR00017##

[0282] Except for using 4-chloro-2-methylquinoline (3.0 g, 16.9 mmol) instead of 4,7-dichloroquinoline, the target compound (2-1, 3.1 g) was obtained as a white solid in the same manner as in the synthesis of Intermediate 1 (1-1).

[0283] White solid (86%), .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.97 (d, J=8.6 Hz, 2H), 7.62 (ddd, J=8.4, 6.9, 1.4 Hz, 1H), 7.42 (ddd, J=8.1, 6.9, 1.1 Hz, 1H), 6.74 (s, 1H), 3.49 (s, 2H), 3.25-3.09 (m, 8H), 2.68 (s, 3H). LC-MS (ESI): Rt=0.93 min, m/z 228.2 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(2-2) Synthesis of tert-butyl 3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidine-1-carboxylate

tert-butyl 3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidine-1-carboxylate

[0284] ##STR00018##

[0285] Except for adding 2-methyl-4-(piperazin-1-yl)quinoline (2.50 g, 11.0 mmol) instead of 7-chloro-4-(piperazin-1-yl)quinoline, the target compound (2-2, 4.8 g) was obtained as a yellow solid in the same manner as in the synthesis of Intermediate 1 (1-2).

[0286] LC-MS (ESI): Rt=1.56 min, m/z 439.5 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(2-3) Synthesis of (4-(2-methylquinolin-4-yl)pyrazin-1-yl)(piperidin-3-yl)methanone

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

[0287] ##STR00019##

[0288] Except for adding tert-butyl 3-(4-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate instead of tert-butyl 3-(1-(2-methylquinoline-4)-yl) piperazine-4-carbonyl) piperidine-1-carboxylate (4.83 g, 11.0 mmol), the target compound (2-3, 3.66 g) was obtained as a yellow solid in the same manner as in the synthesis of Intermediate 1 (1-3).

[0289] LC-MS (ESI): Rt=1.22 min, m/z 339.4 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(3) Synthesis of (R)-(4-(2-methylquinolin-4-yl)pyrazin-1-yl)(piperidin-3-yl)methanone (Intermediate 3)

(3-1) Synthesis of (R)-tert-butyl 3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidine-1-carboxylate

(R)-tert-butyl 3-(4-(2-methylquinolin-4-yl)piperazine-1-carbonyl) piperidine-1-carboxylate

[0290] ##STR00020##

[0291] Except for using (R)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (111 mg, 0.48 mmol) instead of 1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid, the synthesis was carried out in the same manner as in the synthesis of tert-butyl 3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidine-1-carboxylate (2-2), and the target compound (3-1, 190 mg) was obtained as a white solid.

[0292] LC-MS (ESI): Rt=1.55 min, m/z 439.4 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(3-2) Synthesis of (R)-(4-(2-methylquinolin-4-yl)pyrerazin-1-yl)(piperidin-3-yl)methanone

(R)-(4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

[0293] ##STR00021##

[0294] Except for using (R)-tert-butyl 3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidine-1-carboxylate (190 mg, 0.43 mmol) instead of tert-butyl 3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidine-1-carboxylate (2-2), the synthesis was carried out in the same manner as in the synthesis of Intermediate 2-3 to obtain the target compound (3-2, 140 mg) as a white solid.

[0295] LC-MS (ESI): Rt=1.32 min, m/z 339.2 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(4) Synthesis of (S)-(4-(2-methylquinolin-4-yl)pyrazin-1-yl)(piperidin-3-yl)methanone (Intermediate 4)

(S)-(4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

(4-1) Synthesis of (S)-tert-butyl 3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidine-1-carboxylate

(S)-tert-butyl 3-(4-(2-methylquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

[0296] ##STR00022##

[0297] In the same manner as for the synthesis of tert-butyl 3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidine-1-carboxylate (Intermediate 2-2), (S)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (111 mg, 0.48 mmol) was used for synthesis to obtain the target compound (4-1, 180 mg) as a white solid.

[0298] LC-MS (ESI): Rt=1.62 min, m/z 439.3 [M+H].sup.+; purity: 100% @ 254 nm, 97.39% @ 214 nm.

(4-2) Synthesis of (S)-(4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

(S)-(4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

[0299] ##STR00023##

[0300] In the same manner as for the synthesis of (4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone, the target compound (4-2, 140 mg) was obtained as a pale yellow solid using (S)-tert-butyl 3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidine-1-carboxylate (188 mg, 0.43 mmol) according to the method of Synthesis Method 1.

[0301] LC-MS (ESI): Rt=1.28 min, m/z 339.2 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(5) synthesis of piperidin-3-yl (4-(2-(trifluoromethyl) quinolin-4-yl) piperazin-1-yl) methanone (Intermediate 5)

piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

(5-1) Synthesis of 4-(piperazin-1-yl)-2-(prefluoromethyl)quinoline

4-(piperazin-1-yl)-2-(trifluoromethyl)quinoline

[0302] ##STR00024##

[0303] Except for adding 4-chloro-2-(trifluoromethyl)quinoline (3.0 g, 12.9 mmol) instead of 4,7-dichloroquinoline, the target compound (5-1, 3.3 g) was obtained as a yellow solid in the same manner as in the synthesis of Intermediate 1 (1-1).

[0304] 1H MNR: (300 MHz, CDCl.sub.3): δ 8.16 (d, J=8.4 Hz, 1H), 8.05 (d, J=8.4 Hz, 1H), 7.76-7.71 (m, 1H), 7.61-7.56 (m, 1H), 7.14 (s, 1H), 3.31-3.28 (m, 4H), 3.21-3.18 (m, 4H). LC-MS (ESI): Rt=1.40 min, m/z 282.2 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(5-2) Synthesis of tert-butyl 3-(4-(2-(trifluoromethyl)quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

tert-butyl 3-(4-(2-(trifluoromethyl)quinolin-4-yl)piperazine-1-carbonyl) piperidine-1-carboxylate

[0305] ##STR00025##

[0306] Except for adding 4-(piperazin-1-yl)-2-(prefluoromethyl)quinoline (2.5 g, 8.90 mmol) instead of 7-chloro-4-(piperazin-1-yl)quinoline, the target compound (5-2, 4.3 g) was obtained as a yellow solid in the same manner as in the synthesis of Intermediate 1 (1-2).

[0307] LC-MS (ESI): Rt=1.73 min, m/z 492.5 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(5-3) Synthesis of piperidin-3-yl (4-(2-(trifluoromethyl) quinolin-4-yl) piperazin-1-yl) methanone

piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

[0308] ##STR00026##

[0309] Except for adding tert-butyl 3-(4-(2-(trifluoro methyl)quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate (4.35 g, 8.83 mmol) instead of tert-butyl 3-(4-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate, the target compound (5-3, 3.3 g) was obtained as a yellow solid in the same manner as in the synthesis of Intermediate 1 (1-3).

[0310] LC-MS (ESI): Rt=1.39 min, m/z 393.4 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(6) Synthesis of (R)-piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone (Intermediate 6)

(R)-piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

(6-1) Synthesis of (R)-tert-butyl 3-(4-(2-(trifluoromethyl)quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

(R)-tert-butyl 3-(4-(2-(trifluoromethyl)quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

[0311] ##STR00027##

[0312] In the same manner as in the synthesis method of tert-butyl 3-(4-(2-(trifluoromethyl)quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate in (5-2) above, synthesis was carried out using (R)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (134 mg, 0.58 mmol) to obtain the target compound (6-1, 250 mg) as a white solid.

[0313] LC-MS (ESI): Rt=1.81 min, m/z 493.3 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(6-2) Synthesis of (R)-piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

(R)-piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

[0314] ##STR00028##

[0315] In the same manner as for the synthesis of piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone in (5-3) above, the target compound (6-2, 200 mg) was obtained as a yellow solid using (R)-tert-butyl tert-butyl 3-(4-(2-(trifluoromethyl)quinolin-4-yl)piperazine-1-carbonyl) piperidine-1-carboxylate (260 mg, 0.52 mmol) according to the method of Synthesis Method 1.

[0316] LC-MS (ESI): Rt=1.55 min, m/z 393.3 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(7) Synthesis of (S)-piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone (Intermediate 7)

(S)-piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

(7-1) Synthesis of (S)-tert-butyl 3-(4-(2-(trifluoromethyl)quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

(S)-tert-butyl 3-(4-(2-(trifluoromethyl)quinolin-4-yl)piperazine-1-carbonyl) piperidine-1-carboxylate

[0317] ##STR00029##

[0318] In the same manner as in the synthesis method of tert-butyl 3-(4-(2-(trifluoromethyl)quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate in (5-2) above, synthesis was carried out using (S)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (134 mg, 0.58 mmol) to obtain the target compound (7-1, 250 mg) as a white solid.

[0319] LC-MS (ESI): Rt=1.80 min, m/z 493.3 [M+H].sup.+; purity: 100% @ 254 nm, 97.39% @ 214 nm.

(7-2) Synthesis of (S)-piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

(S)-piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

[0320] ##STR00030##

[0321] In the same manner as in the synthesis method of tert-butyl 3-(4-(2-(trifluoromethyl)quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate in (5-3) above, the target compound (7-2, 200 mg) was obtained as a white solid using (S)-tert-butyl tert-butyl 3-(4-(2-(trifluoromethyl)quinolin-4-yl)piperazine-1-carbonyl) piperidine-1-carboxylate (260 mg, 0.52 mmol) according to the method of Synthesis Method 1.

[0322] LC-MS (ESI): Rt=1.56 min, m/z 393.3 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(8) Synthesis of (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone (Intermediate 8)

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

(8-1) Synthesis of 7-fluoro-4-(piperazin-1-yl) quinoline

7-fluoro-4-(piperazin-1-yl)quinoline

[0323] ##STR00031##

[0324] Except for adding 4-chloro-7-fluoroquinoline (4.0 g, 22.0 mmol) instead of 4,7-dichloroquinoline, the target compound (8-1, 4.5 g) was obtained as a white solid in the same manner as in the synthesis of Intermediate 1 (1-1).

[0325] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 8.82 (d, J=6.9 Hz, 1H), 8.36-8.81 (m, 1H), 8.04-8.00 (m, 1H), 7.67-7.61 (m, 1H), 7.34 (d, J=6.6 Hz, 1H), 4.03-3.90 (m, 4H), 3.59-3.38 (m, 4H). Rt=1.12 min, m/z 232.2 [M+H].sup.+. purity: 100% @ 254 nm, 100.0% @214 nm.

(8-2) Synthesis of tert-butyl 3-(4-(7-fluoroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

tert-butyl 3-(4-(7-fluoroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

[0326] ##STR00032##

[0327] Except for adding 7-fluoro-4-(piperazin-1-yl)quinoline (1.5 g, 5.60 mmole) instead of 7-chloro-4-(piperazin-1-yl)quinoline, the target compound (8-2, 2.4 g) was obtained as a dark yellow solid in the same manner as in the synthesis of Intermediate 1 (1-2).

[0328] LC-MS (ESI): Rt=1.33 min, m/z 443.4 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(8-3) Synthesis of (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

[0329] ##STR00033##

[0330] Except for adding tert-butyl 3-(4-(7-fluoroquinoline-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate (2.48 g, 5.60 mmol) instead of tert-butyl 3-(4-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate, the target compound (8-3, 1.6 g) was obtained as a yellow solid in the same manner as in the synthesis of Intermediate 1 (1-3).

[0331] LC-MS (ESI): Rt=1.04 min, m/z 343.4 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(9) Synthesis of (R)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone (Intermediate 9)

(R)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

(9-1) Synthesis of (R)-tert-butyl 3-(4-(7-fluoroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

(R)-tert-butyl 3-(4-(7-fluoroquinolin-4-yl)piperazine-1-carbonyl) piperidine-1-carboxylate

[0332] ##STR00034##

[0333] In the same manner as for the synthesis of tert-butyl 3-(4-(7-fluoroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate in (8-2) above, synthesis was carried out using (R)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (297 mg, 1.3 mmol) to obtain the target compound (9-1, 190 mg) as a white solid.

[0334] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.76-8.74 (m, 1H), 8.05-8.01 (m, 1H), 7.72-7.69 (m, 1H), 7.33-7.27 (m, 1H), 6.84-6.82 (m, 1H), 4.20-4.08 (m, 2H), 3.90-3.84 (m, 4H), 3.25-3.19 (m, 4H), 2.87-2.67 (m, 3H), 1.94-1.91 (m, 1H), 1.84-1.74 (m, 3H), 1.47 (s, 9H). LC-MS (ESI): Rt=1.64 min, m/z 443.6 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

[0335] chiral HPLC: Column: Chiralpak IA 5 um 4.6×250 mm; Mobile Phase: Hex:EtOH=30:70 at 1 mL/min; Temp: 30° C.; Wavelength: 230 nm, Rt=10.321 min, 99.58% ee.

(9-2) Synthesis of (R)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

(R)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

[0336] ##STR00035##

[0337] In the same manner as for the synthesis of (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone in (8-3) above, the target compound (9-2, 140 mg) was obtained as a white solid using (R)-tert-butyl 3-(4-(7-fluoroquinolin-4-yl)piperazine-4-carbonyl)piperidine-1-carboxylate (400 mg, 0.9 mmol) according to the method of Synthesis Method 1.

[0338] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 8.73-8.67 (m, 2H), 8.36-8.33 (m, 1H), 7.81-7.78 (m, 1H), 7.65-7.60 (m, 1H), 7.18 (d, J=7.2 Hz, 1H), 3.98-3.94 (m, 4H), 3.84-3.76 (m, 4H), 3.23-2.98 (m, 5H), 1.92-1.54 (m, 4H). LC-MS (ESI): Rt=1.30 min, m/z 343.5 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(10) Synthesis of (S)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone (intermediate 10)

(S)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

(10-1) Synthesis of (S)-tert-butyl 3-(4-(7-fluoroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

(S)-tert-butyl 3-(4-(7-fluoroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

[0339] ##STR00036##

[0340] In the same manner as for the synthesis of tert-butyl 3-(4-(7-fluoroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate in (8-2) above, synthesis was carried out using (S)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (297 mg, 1.3 mmol) to obtain the target compound (10-1, 180 mg) as a white solid.

[0341] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.75 (d, J=4.8 Hz, 1H), 8.05-8.01 (m, 1H), 7.72-7.69 (m, 1H), 7.33-7.28 (m, 1H), 6.83 (d, J=4.8 Hz, 1H), 4.21-4.06 (m, 2H), 3.99-3.81 (m, 4H), 3.25-3.19 (m, 4H), 2.98-2.68 (m, 3H), 2.04-1.95 (m, 1H), 1.91-1.74 (m, 3H), 1.47 (s, 9H). LC-MS (ESI): Rt=1.57 min, m/z 443.5 [M+H].sup.+; purity: 100% @ 254 nm, 97.39% @ 214 nm.

(10-2) Synthesis of (S)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

(S)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

[0342] ##STR00037##

[0343] In the same manner as for the synthesis of (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone in (8-3) above, synthesis was carried out using (S)-tert-butyl 3-(4-(7-fluoroquinolin-4-yl)piperazine-4-carbonyl)piperidine-1-carboxylate (380 mg, 0.86 mmol) to obtain the target compound (10-2, 140 mg) as a white solid.

[0344] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.73-8.71 (m, 2H), 8.37-8.33 (m, 1H), 7.81-7.78 (m, 1H), 7.65-7.60 (m, 1H), 7.19 (d, J=6.8 Hz, 1H), 4.00-3.77 (m, 8H), 3.24-2.94 (m, 5H), 1.96-1.59 (m, 4H). LC-MS (ESI): Rt=1.38 min, m/z 343.5 [M+H].sup.+; purity: 98% @254 nm, 100% @ 214 nm.

(11) synthesis of piperidin-3-yl (4-(quinolin-4-yl) piperazin-1-yl) methanone (intermediate 11)

piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone

(11-1) Synthesis of tert-butyl 3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

tert-butyl 3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

[0345] ##STR00038##

[0346] Except for adding 4-(piperazin-1-yl)quinoline di-HCl salt (1.50 g, 5.24 mmol) instead of 7-chloro-4-(piperazin-1-yl)quinoline, the target compound (11-1, 2.1 g) was obtained as a dark yellow solid in the same manner as in the synthesis of Intermediate 1 (1-2).

[0347] LC-MS (ESI): Rt=1.31 min, m/z 425.4 [M+H].sup.+; purity: 100% @ 254 nm, 95.1% @ 214 nm.

(11-2) Synthesis of piperidin-3-yl (4-(quinolin-4-yl) piperazin-1-yl) methanone

piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0348] ##STR00039##

[0349] Except for adding tert-butyl 3-(4-(quinolin-4-yl) piperazine-1-carbonyl)piperidine-1-carboxylate (2.2 g, 5.18 mmol) instead of tert-butyl 3-(4-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate, the target compound (11-2, 1.6 g) was obtained as a yellow solid in the same manner as in the synthesis of Intermediate 1 (1-3).

[0350] .sup.1H MNR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.8 Hz, 1H), 8.08 (d, J=8.4 Hz, 1H), 8.02 (d, J=8.8 Hz, 1H), 7.71-7.67 (m, 1H), 7.55-7.51 (m, 1H), 6.85 (d, J=5.2 Hz, 1H), 3.91-3.83 (m, 4H), 3.24-3.17 (m, 5H), 3.13-3.09 (m, 2H), 3.04-2.98 (m, 1H), 2.95-2.88 (m, 1H), 2.81-2.75 (m, 1H), 1.95-1.92 (m, 1H), 1.82-1.75 (m, 1H), 1.72-1.65 (m, 1H). LC-MS (ESI): Rt=1.00 min, m/z 325.3 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(12) Synthesis of (R)-piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone (Intermediate 12)

(R)-piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone

(12-1) Synthesis of (R)-tert-butyl 3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

(R)-tert-butyl 3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

[0351] ##STR00040##

[0352] In the same manner as in the synthesis method of tert-butyl 3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate in (11-1) above, synthesis was carried out using (R)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (500 mg, 2.2 mmol) to obtain the target compound (12-1, 400 mg) as a white solid.

[0353] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.8 Hz, 1H), 8.09 (d, J=8.4 Hz, 1H), 8.03 (d, J=8.4 Hz, 1H), 7.69 (t, J=8.0 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H), 6.86 (d, J=5.2 Hz, 1H), 4.27-4.05 (m, 2H), 3.92-3.83 (m, 4H), 3.31-3.21 (m, 4H), 2.94-2.65 (m, 3H), 1.95-1.92 (m, 1H), 1.84-1.73 (m, 3H), 1.47 (s, 9H). LC-MS (ESI): Rt=1.28 min, m/z 425.4 [M+H].sup.+; purity: 100% @ 254 nm, 95.1% @ 214 nm.

(12-2) Synthesis of (R)-piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone

(R)-piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0354] ##STR00041##

[0355] In the same manner as in the synthesis method of (11-2) piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone, the target compound (12-2, 280 mg) was obtained as a yellow solid using (R)-tert-butyl 3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate (600 mg, 1.41 mmol) according to the method of Synthesis Method 1.

[0356] LC-MS (ESI): Rt=0.28 min, m/z 325.3 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(13) Synthesis of (S)-piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone (Intermediate 13)

(S)-piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone

(13-1) Synthesis of (S)-tert-butyl 3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

(S)-tert-butyl 3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

[0357] ##STR00042##

[0358] In the same manner as in the synthesis method of tert-butyl 3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate in (11-1) above, synthesis was carried out using (S)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (500 mg, 2.2 mmol) to obtain the target compound (13-1, 380 mg) as a yellow solid.

[0359] .sup.1HNMR (400 MHz, CDCl.sub.3): .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.8 Hz, 1H), 8.10-8.02 (m, 2H), 7.69 (t, J=7.2 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H), 6.86 (d, J=5.2 Hz, 1H), 4.25-4.11 (m, 2H), 3.91-3.80 (m, 4H), 3.62-3.21 (m, 4H), 2.94-2.84 (m, 1H), 2.68-2.63 (m, 2H), 1.97-1.92 (m, 1H), 1.88-1.73 (m, 3H), 1.47 (s, 9H). LC-MS (ESI): Rt=1.27 min, m/z 425.4 [M+H].sup.+; purity: 100% @ 254 nm, 95.1% @ 214 nm.

(13-2) Synthesis of (S)-piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone

(S)-piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0360] ##STR00043##

[0361] In the same manner as in the synthesis method of piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone in (11-2) above, the target compound (13-2, 250 mg) was obtained as a yellow solid using (S)-tert-butyl 3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate (600 mg, 1.41 mmol) according to the method of Synthesis Method 1.

[0362] LC-MS (ESI): Rt=0.28 min, m/z 325.3 [M+H].sup.+; purity: 100% @ 254 nm, 99.5% @ 214 nm.

(14) Synthesis of (4-(7-methoxyquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone (Intermediate 14)

(4-(7-methoxyquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

(14-1) Synthesis of 7-methoxy-4-(piperazin-1-yl) quinoline

7-methoxy-4-(piperazin-1-yl)quinoline

[0363] ##STR00044##

[0364] Except for adding 4-chloro-2-methoxyquinoline (3.00 g, 15.5 mmol) instead of 4,7-dichloroquinoline, the target compound (14-1, 3.1 g) was obtained as a yellow solid in the same manner as in the synthesis of Intermediate 1 (1-1).

[0365] 1H MNR: (400 MHz, CDCl.sub.3): δ 8.68 (d, J=6.8 Hz, 1H), 7.94 (d, J=12.4 Hz, 1H), 7.40 (d, J=3.2 Hz, 1H), 7.15 (dd, J=12.0, 3.6 Hz, 1H), 6.76 (d, J=6.8 Hz, 1H), 3.97 (s, 3H), 3.19-3.18 (m, 8H), 1.87 (s, 1H). LC-MS (ESI): Rt=1.213 min, m/z 224.1 [M+H].sup.+; purity: 100% @ 254 nm, 97% @ 214 nm.

(14-2) Synthesis of tert-butyl 3-(4-(7-methoxyquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

tert-butyl 3-(4-(7-methoxyquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate

[0366] ##STR00045##

[0367] Except for adding 7-methoxy-4-(piperazin-1-yl)quinoline (1.50 g, 6.17 mmol) instead of 7-chloro-4-(piperazin-1-yl)quinoline, the target compound (14-2, 2.7 g) was obtained as a dark yellow solid in the same manner as in the synthesis of Intermediate 1 (1-2).

[0368] LC-MS (ESI): Rt=1.61 min, m/z 455.4 [M+H].sup.+; purity: 100% @ 254 nm, 93% @ 214 nm.

(14-3) Synthesis of (4-(7-methoxyquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

(4-(7-methoxyquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone

[0369] ##STR00046##

[0370] Except for adding tert-butyl 3-(4-(7-methoxyquinoline-4-yl) piperazine-1-carbonyl) piperidine-1-carboxylate (2.75 g, 6.04 mmol) instead of Tert-butyl 3-(4-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidine-1-carboxylate, the target compound (14-3, 1.8 g) was obtained as a yellow solid in the same manner as in the synthesis of Intermediate 1 (1-3).

[0371] LC-MS (ESI): Rt=1.30 min, m/z 355.4 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

(15) Synthesis of 1-((4-acetamidophenyl)sulfonyl)piperidine-3-carboxylic acid (Intermediate 15)

1-(4-acetamidophenylsulfonyl)piperidine-3-carboxylic acid

[0372] ##STR00047##

[0373] According to Reaction Scheme 2, 4-acetamidobenzenesulfonyl chloride (3.0 g, 12.84 mmol), nipecotic acid (2.5 g, 19.36 mmol), sodium carbonate (51.4 mmol, 4 eq) were added to 60 ml of THE/water (1:1), and stir at room temperature for 12 hours. Then, tetrahydrofuran (THF) was concentrated under reduced pressure, ethyl acetate (50 ml) was added, and 1 N hydrochloric acid solution was added to adjust pH to 2. The organic layer was separated, dried over Na.sub.2SO, filtered, concentrated under reduced pressure, and purified using column chromatography (MeOH 5%). As a result, Intermediate 15 (2.9 g) was obtained as a white solid.

[0374] .sup.1H NMR (400 MHz, MeOH-d4) δ 7.87-7.79 (m, 2H), 7.77-7.71 (m, 2H), 3.71 (d, J=7.8 Hz, 1H), 3.54-3.45 (m, 1H), 2.65-2.53 (m, 2H), 2.47 (td, J=11.2, 3.0 Hz, 1H), 2.18 (d, J=2.2 Hz, 3H), 2.00-1.90 (m, 1H), 1.86-1.79 (m, 1H), 1.63 (ddd, J=9.8, 7.0, 3.4 Hz, 1H), 1.49-1.40 (m, 1H).

(16) Synthesis of 1-((4-nitrophenyl)sulfonyl)piperidine-3-carboxylic acid (Intermediate 16)

1-(4-nitrophenylsulfonyl)piperidine-3-carboxylic acid

[0375] ##STR00048##

[0376] According to Reaction Formula 2, 4-nitrobenzene chloride (2.0 g, 9.02 mmol) was used instead of 4-acetamidobenzenesulfonyl chloride to obtain an intermediate (16, 1.7 g) as a yellow solid by the method of Reaction Formula 2.

[0377] .sup.1H NMR (400 MHz, MeOH-d4) δ 8.59-8.53 (m, 2H), 8.24-8.16 (m, 1H), 7.92 (dd, J=8.5, 7.8 Hz, 1H), 3.76 (dd, J=11.6, 3.8 Hz, 1H), 3.62-3.51 (m, 1H), 2.79-2.71 (m, 1H), 2.62 (dd, J=16.5, 6.2 Hz, 2H), 2.02-1.93 (m, 1H), 1.88-1.80 (m, 1H), 1.74-1.56 (m, 2H), 1.50 (ddd, J=24.4, 10.6, 3.7 Hz, 1H).

Example 2: Synthesis of Quinoline-Based Target Material

[0378] The target compound was synthesized according to Reaction Formula 1-1 for the following example compounds.

##STR00049## ##STR00050##

##STR00051##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-(phenylsulfonyl)piperidin-3-yl)methanone

[0379] To a solution in which (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone (180 mg, 0.50 mmol) and TEA (152 mg, 1.50 mmol) in dichloromethane (DCM, 3 mL) was slowly added benzenesulfonyl chloride (133 mg, 0.75 mmol) diluted in dichloromethane (1 mL) at room temperature for 2 hours stir while. After the mixture was concentrated under reduced pressure, the residue was first purified using C18 chromatography using 40˜90% CH.sub.3CN (acetonitrile) aqueous solution as a developing solvent, followed by ethyl acetate (EtOAc) and n-hexane (n-hexane) to recrystallize, and the target compound (Formula 1, 160 mg) was obtained as a white solid.

[0380] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.73 (d, J=5.2 Hz, 1H), 8.12 (d, J=9.2 Hz, 1H), 8.00 (d, J=2.4 Hz, 1H), 7.77-7.73 (m, 3H), 7.70-7.66 (m, 2H), 7.60 (dd, J=8.8, 2.0 Hz, 1H), 7.05 (d, J=5.2 Hz, 1H), 3.79-3.64 (m, 6H), 3.26-3.21 (m, 4H), 2.98-2.92 (m, 1H), 2.33 (t, J=11.6 Hz, 1H), 2.22-2.16 (m, 1H), 1.82-1.73 (m, 2H), 1.66-1.57 (m, 1H), 1.28-1.18 (m, 1H). LC-MS (ESI): Rt=3.906 min, m/z 499.2 [M+H].sup.+; purity: 99.40% @ 254 nm, 99.75% @ 214 nm.

##STR00052##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-tosylpiperidin-3-yl)methanone

[0381] Except for using 4-methylbenzene-1-sulfonyl chloride (80 mg, 0.42 mmol) instead of benzenesulfonyl chloride, Formula 2 (75 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 1 above.

[0382] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.8 Hz, 1H), 8.08 (d, J=2.4 Hz, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.65 (d, J=8.4 Hz, 2H), 7.48 (dd, J=9.2, 2.4 Hz, 1H), 7.33 (d, J=8.0 Hz, 2H), 7.05 (d, J=5.2 Hz, 1H), 6.86 (d, J=5.2 Hz, 1H), 3.88-3.78 (m, 6H), 3.26-3.18 (m, 4H), 2.95-2.88 (m, 1H), 2.49 (t, J=11.2 Hz, 1H), 2.23 (td, J=13.2, 2.8 Hz, 1H), 1.89-1.82 (m, 2H), 1.80-1.68 (m, 1H), 1.54-1.44 (m, 1H). LC-MS (ESI): Rt=2.390 min, m/z 513.2 [M+H].sup.+; purity: 99.71% @ 254 nm, 99.67% @ 214 nm.

##STR00053##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((4-fluorophenyl)sulfonyl) piperidin-3-yl)methanone

[0383] Except for using 4-fluorobenzene-1-sulfonyl chloride (65 mg, 0.33 mmol) instead of benzenesulfonyl chloride, Formula 3 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 1 above.

[0384] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 8.74 (d, J=4.8 Hz, 1H), 8.11 (d, J=8.8 Hz, 1H), 8.01 (d, J=2.4 Hz, 1H), 7.85-7.82 (m, 2H), 7.59 (dd, J=8.8, 2.4 Hz, 1H), 7.54-7.50 (m, 2H), 7.04 (d, J=5.2 Hz, 1H), 3.80-3.64 (m, 6H), 3.23-3.13 (m, 4H), 2.99-2.94 (m, 1H), 2.34 (t, J=11.2 Hz, 1H), 2.24-2.18 (m, 1H), 1.82-1.73 (m, 2H), 1.66-1.56 (m, 1H), 1.29-1.93 (m, 1H). LC-MS (ESI): Rt=3.343 min, m/z 517.2 [M+H].sup.+; purity: 99.07% @ 254 nm, 99.67% @ 214 nm.

##STR00054##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((4-(dimethylamino)phenyl) sulfonyl)piperidin-3-yl)methanone

[0385] Except for using 4-(methylamino)benzene-1-sulfonyl chloride (54 mg, 0.25 mmol) instead of benzenesulfonyl chloride, Formula 4 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 1 above.

[0386] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.4 Hz, 1H), 8.07-8.07 (m, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.60-7.57 (m, 2H), 7.47 (dd, J=8.8, 2.0 Hz, 1H), 6.86 (d, J=4.8 Hz, 1H), 6.69-6.67 (m, 1H), 3.88-3.80 (m, 6H), 3.24-3.18 (m, 4H), 3.05 (s, 6H), 2.95-2.88 (m, 1H), 2.45 (t, J=11.2 Hz, 1H), 2.23-2.17 (m, 1H), 1.87-1.81 (m, 2H), 1.77-1.71 (m, 1H), 1.53-1.42 (m, 1H). LC-MS (ESI): Rt=2.941 min, m/z 542.2 [M+H].sup.+; purity: 99.81% @ 254 nm, 99.63% @ 214 nm.

##STR00055##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((4-hydroxyphenyl)sulfonyl) piperidin-3-yl)methanone

[0387] Except for using 4-hydroxybenzene-1-sulfonyl chloride (97 mg, 0.50 mmol) instead of benzenesulfonyl chloride, Formula 5 (40 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 1 above.

[0388] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 10.50 (br, 1H), 8.73 (d, J=5.2 Hz, 1H), 8.10 (d, J=10.4 Hz, 1H), 8.00 (d, J=2.0 Hz, 1H), 7.60-7.54 (m, 3H), 7.03 (d, J=4.8 Hz, 1H), 6.95 (d, J=8.8 Hz, 2H), 3.79-3.72 (m, 4H), 3.61-3.57 (m, 2H), 3.20-3.14 (m, 4H), 2.96-2.90 (m, 1H), 2.28 (t, J=11.6 Hz, 1H), 2.16-2.11 (m, 1H), 1.80-1.72 (m, 2H), 1.65-1.55 (m, 1H), 1.26-1.17 (m, 1H). LC-MS (ESI): Rt=3.217 min, m/z 515.2 [M+H].sup.+; purity: 97.98% @ 254 nm, 97.82% @ 214 nm.

##STR00056##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((3-nitrophenyl)sulfonyl) piperidin-3-yl)methanone

[0389] Except for using 3-nitrobenzene-1-sulfonyl chloride (54 mg, 0.25 mmol) instead of benzenesulfonyl chloride, Formula 6 (60 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 1 above.

[0390] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.73 (d, J=5.2 Hz, 1H), 8.58-8.55 (m, 1H), 8.39 (t, J=1.6 Hz, 1H), 8.22-8.20 (m, 1H), 8.11 (d, J=9.2 Hz, 1H), 8.01-7.96 (m, 2H), 7.59 (dd, J=9.2, 2.4 Hz, 1H), 7.04 (d, J=5.2 Hz, 1H), 3.85-3.80 (m, 2H), 3.72-3.71 (m, 4H), 3.22-3.19 (m, 4H), 3.00-2.94 (m, 1H), 2.50-2.46 (m, 1H), 2.41-2.35 (m, 1H), 1.83-1.74 (m, 2H), 1.64-1.61 (m, 1H), 1.32-1.23 (m, 1H). LC-MS (ESI): Rt=3.339 min, m/z 544.1 [M+H].sup.+; purity: 99.16% @ 254 nm, 99.19% @ 214 nm.

##STR00057##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((4-(trifluoromethyl)phenyl) sulfonyl)piperidin-3-yl)methanone

[0391] Except for using 4-(fluoromethyl)benzene-1-sulfonyl chloride (60 mg, 0.25 mmol) instead of benzenesulfonyl chloride, Formula 7 (60 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 1 above.

[0392] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.74 (d, J=4.8 Hz, 1H), 8.12-8.05 (m, 3H), 8.01-7.97 (m, 3H), 7.60-7.58 (m, 1H), 7.04 (d, J=5.2 Hz, 1H), 3.80-3.67 (m, 6H), 3.26-3.14 (m, 4H), 3.00-2.94 (m, 1H), 2.42 (t, J=10.8 Hz, 1H), 2.32-2.27 (m, 1H), 1.82-1.74 (m, 2H), 1.65-1.62 (m, 1H), 1.32-1.23 (m, 1H). LC-MS (ESI): Rt=4.056 min, m/z 567.2 [M+H].sup.+; purity: 97.21% @ 254 nm, 97.88% @ 214 nm.

##STR00058##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((3-fluorophenyl)sulfonyl) piperidin-3-yl)methanone

[0393] Except for using 3-fluorobenzene-1-sulfonyl chloride (65 mg, 0.33 mmol) instead of benzenesulfonyl chloride, Formula 8 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 1 above.

[0394] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.74 (d, J=4.8 Hz, 1H), 8.11 (d, J=9.2 Hz, 1H), 8.01 (d, J=2.4 Hz, 1H), 7.77-7.72 (m, 1H), 7.65-7.57 (m, 4H), 7.04 (d, J=4.8 Hz, 1H), 3.80-3.66 (m, 6H), 3.26-3.14 (m, 4H), 2.99-2.93 (m, 1H), 2.39 (t, J=11.6 Hz, 1H), 2.30-2.24 (m, 1H), 1.82-1.73 (m, 2H), 1.67-1.60 (m, 1H), 1.31-1.20 (m, 1H). LC-MS (ESI): Rt=3.758 min, m/z 517.2 [M+H].sup.+; purity: 99.12% @ 254 nm, 99.26% @214 nm.

##STR00059##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((4-phenoxyphenyl)sulfonyl) piperidin-3-yl)methanone

[0395] Except for using 4-phenoxybenzene-1-sulfonyl chloride (66 mg, 0.25 mmol) instead of benzenesulfonyl chloride, Formula 9 (80 mg) was obtained as a white solid in the same manner as in the preparation of compound of Formula 1 above.

[0396] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.73 (d, J=5.2 Hz, 1H), 8.10 (d, J=8.8 Hz, 1H), 8.01-8.00 (m, 1H), 7.76-7.74 (m, 2H), 7.58 (dd, J=8.8, 2.0 Hz, 1H), 7.50-7.46 (m, 2H), 7.30-7.26 (m, 1H), 7.19-7.16 (m, 4H), 7.03 (d, J=4.8 Hz, 1H), 3.78-3.62 (m, 6H), 3.21-3.14 (m, 4H), 2.99-2.93 (m, 1H), 2.34 (t, J=11.6 Hz, 1H), 2.24-2.18 (m, 1H), 1.82-1.74 (m, 2H), 1.67-1.57 (m, 1H), 1.29-1.20 (m, 1H). LC-MS (ESI): Rt=3.939 min, m/z 591.2 [M+H].sup.+; purity: 99.66% @ 254 nm, 99.64% @ 214 nm.

##STR00060##

4-(3-(1-(7-chloroquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)benzonitrile

[0397] Except for using 4-cyanobenzene-1-sulfonyl chloride (50 mg, 0.25 mmol) instead of benzenesulfonyl chloride, Formula 10 (65 mg) was obtained as a white solid in the same manner as in the preparation of compound of Formula 1 above.

[0398] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=5.2 Hz, 1H), 8.08 (d, J=1.6 Hz, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.89-7.83 (m, 4H), 7.47 (dd, J=8.8, 1.6 Hz, 1H), 6.86 (d, J=5.2 Hz, 1H), 3.91-3.82 (m, 6H), 3.26-3.18 (m, 4H), 2.95-2.89 (m, 1H), 2.59 (t, J=11.2 Hz, 1H), 2.30 (td, J=12.0, 2.0 Hz, 1H), 1.94-1.85 (m, 2H), 1.77-1.73 (m, 1H), 1.59-1.48 (m, 1H). LC-MS (ESI): Rt=3.170 min, m/z 524.2 [M+H].sup.+; purity: 99.73% @ 254 nm, 99.40% @ 214 nm.

##STR00061##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-(4-(methylsulfonyl)phenylsulfonyl)piperidin-3-yl)methanone

[0399] Except for using 4-(methylsulfonyl)benzene-1-sulfonyl chloride (63 mg, 0.25 mmol) instead of benzenesulfonyl chloride, Formula 11 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 1.

[0400] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=4.8 Hz, 1H), 8.14-8.08 (m, 3H), 7.98-7.94 (m, 3H), 7.47 (d, J=8.0 Hz, 1H), 6.86 (d, J=4.8 Hz, 1H), 3.92-3.82 (m, 6H), 3.23-3.18 (m, 4H), 2.94-2.89 (m, 1H), 2.61 (t, J=11.6 Hz, 1H), 2.33 (t, J=10.8 Hz, 1H), 1.94-1.86 (m, 2H), 1.77-1.73 (m, 1H), 1.56-0.44 (m, 1H). LC-MS (ESI): Rt=2.987 min, m/z 577.2 [M+H].sup.+; purity: 99.76% @ 254 nm, 98.53% @ 214 nm.

##STR00062##

methyl 4-((3-(1-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidin-1-yl)sulfonyl)benzoate

[0401] Except for using methyl 4-(chlorosulfonyl)benzoate (108 mg, 0.46 mmol) instead of benzenesulfonyl chloride, Formula 12 (90 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 1.

[0402] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.8 Hz, 1H), 8.19 (d, J=8.0 Hz, 2H), 8.08 (s, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.83 (d, J=8.0 Hz, 2H), 7.47 (dd, J=9.2, 1.6 Hz, 1H), 6.86 (d, J=4.8 Hz, 1H), 3.97 (s, 3H), 3.92-3.82 (m, 6H), 3.26-3.18 (m, 4H), 2.94-2.89 (m, 1H), 2.55 (t, J=11.2 Hz, 1H), 2.28 (t, J=12.0 Hz, 1H), 1.92-1.83 (m, 2H), 1.79-1.72 (m, 1H), 1.53-1.44 (m, 1H). LC-MS (ESI): Rt=3.898 min, m/z 557.2 [M+H].sup.+; purity: 98.44% @ 254 nm, 97.77% @ 214 nm.

##STR00063##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-(4-phenylbenzenesulfonyl)piperidin-3-yl)methanone

[0403] Except for using methyl [1,1′-biphenyl]-4-sulfonyl chloride (62 mg, 0.25 mmol) instead of benzenesulfonyl chloride, Formula 13 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 1 above.

[0404] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.8 Hz, 1H), 8.08 (d, J=2.0 Hz, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.82 (d, J=8.4 Hz, 2H), 7.73 (d, J=8.4 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 7.51-7.47 (m, 3H), 7.46-7.42 (m, 1H), 6.86 (d, J=5.2 Hz, 1H), 3.93-3.83 (m, 6H), 3.25-3.19 (m, 4H), 2.96-2.91 (m, 1H), 2.58 (t, J=11.2 Hz, 1H), 2.32 (td, J=8.0, 2.4 Hz, 1H), 1.88-1.84 (m, 2H), 1.77-1.73 (m, 1H), 1.53-1.49 (m, 1H). LC-MS (ESI): Rt=3.107 min, m/z 575.1 [M+H].sup.+; purity: 98.55% @ 254 nm, 98.72% @ 214 nm.

##STR00064##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-(3-methoxyphenyl) sulfonyl)piperidin-3-yl)methanone

[0405] Except for using 3-methoxybenzene-1-sulfonyl chloride (95 mg, 0.46 mmol) instead of benzenesulfonyl chloride, Formula 14 (50 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 1 above.

[0406] LC-MS (ESI): Rt=1.68 min, m/z 529.2 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

##STR00065##

N-(4-(3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)phenyl)acetamide

[0407] To a solution in which (4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone (180 mg, 0.53 mmol) and TEA (152 mg) in DCM (2 mL) was slowly 4-acetamidobenzene-1-sulfonyl chloride (59 mg, 0.25 mmol) diluted in DCM (1 mL) at room temperature for 2 hours stir while. After the mixture was concentrated under reduced pressure, the residue was first purified using C18 chromatography using 40 90% CH.sub.3CN (acetonitrile) aqueous solution as a developing solvent to obtain the target compound of Formula 15 (70 mg).

[0408] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.04 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.83 (s, 1H), 7.71-7.64 (m, 5H), 7.47 (t, J=8.0 Hz, 1H), 6.75 (s, 1H), 3.87-3.82 (m, 6H), 3.27-3.21 (m, 4H), 2.93-2.87 (m, 1H), 2.71 (s, 3H), 2.50 (t, J=11.2 Hz, 1H), 2.28-2.24 (m, 1H), 2.22 (s, 3H), 1.90-1.73 (m, 3H), 1.53-1.45 (m, 1H). LC-MS (ESI): Rt=3.394 min, m/z 536.3 [M+H].sup.+; purity: 99.42% @ 254 nm, 99.71% @ 214 nm.

##STR00066##

(R)—N-(4-((3-(4-(2-methylquinolin-4-yl)piperazine-1-carbonyl)piperidin-1-yl)sulfonyl)phenyl)acetamide

[0409] Except for using (R)-(4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone (70 mg) instead of (4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone, Formula 16 (90 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15

[0410] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.02-7.95 (m, 2H), 7.84-7.78 (m, 1H), 7.73-7.70 (m, 4H), 7.65 (t, J=7.2 Hz, 1H), 7.47 (t, J=7.2 Hz, 1H), 6.76 (s, 1H), 3.88-3.79 (m, 6H), 3.25-3.18 (m, 4H), 2.95-2.88 (m, 1H), 2.70 (s, 3H), 2.50 (t, J=11.2 Hz, 1H), 2.28-2.24 (m, 1H), 2.22 (s, 3H), 1.91-1.83 (m, 2H), 1.77-1.71 (m, 1H), 1.53-1.44 (m, 1H). LC-MS (ESI): Rt=3.540 min, m/z 536.3 [M+H].sup.+; purity: 96.69% @ 254 nm, 98.68% @ 214 nm.

[0411] chiral HPLC: Column: Chiralpak IB 5 um 4.6×250 mm; Mobile Phase: Hex EtOH=60:40 at 1 mL/min; Temp: 30° C.; Wavelength: 254 nm, Rt=11.523 min, 99.45% ee

##STR00067##

(S)—N-(4-((3-(4-(2-methylquinolin-4-yl)piperazine-1-carbonyl)piperidin-1-yl)sulfonyl)phenyl)acetamide

[0412] Except for using (S)-(4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone (70 mg) instead of (4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone, Formula 17 (80 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0413] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.01-7.95 (m, 2H), 7.90 (br s, 1H), 7.70-7.67 (m, 4H), 7.65-7.63 (m, 1H), 7.47 (t, J=7.2 Hz, 1H), 6.76 (s, 1H), 3.88-3.83 (m, 6H), 3.29-3.18 (m, 4H), 2.94-2.88 (m, 1H), 2.70 (s, 3H), 2.50 (t, J=11.2 Hz, 1H), 2.28-2.23 (m, 1H), 2.22 (s, 3H), 1.91-1.83 (m, 2H), 1.77-1.73 (m, 1H), 1.53-1.43 (m, 1H). LC-MS (ESI): Rt=3.354 min, m/z 536.3 [M+H].sup.+; purity: 98.62% @ 254 nm, 98.95% @ 214 nm.

[0414] chiral HPLC: Column: Chiralpak IB 5 um 4.6×250 mm; Mobile Phase: Hex EtOH=60:40 at 1 mL/min; Temp: 30° C.; Wavelength: 254 nm, Rt=9.466 min, 99.16% ee.

##STR00068##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(4-nitrophenylsulfonyl) piperidin-3-yl)methanone

[0415] Except for using 4-nitrobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 18 was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0416] 1H NMR (400 MHz, CDCl.sub.3): δ 8.39 (d, J=8.8 Hz, 2H), 8.02-7.95 (m, 4H), 7.66 (t, J=8.0 Hz, 1H), 7.47 (t, J=8.0 Hz, 1H), 6.75 (s, 1H), 3.95-3.76 (m, 6H), 3.32-3.19 (m, 4H), 2.98-2.91 (m, 1H), 2.70 (s, 3H), 2.61 (t, J=11.2 Hz, 1H), 2.36-2.29 (m, 1H), 1.96-1.87 (m, 2H), 1.82-1.75 (m, 1H), 1.55-1.49 (m, 1H). LC-MS (ESI): Rt=3.153 min, m/z 524.2 [M+H].sup.+; purity: 96.71% @ 254 nm, 97.49% @ 214 nm.

##STR00069##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(phenylsulfonyl)piperidin-3-yl)methanone

[0417] Except for using benzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 19 (40 mg) was obtained as a white solid in the same manner as for the preparation of the compound of Formula 15.

[0418] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.02-7.95 (m, 2H), 7.77 (d, J=7.6 Hz, 2H), 7.68-7.60 (m, 2H), 7.56-7.53 (m, 2H), 7.46 (t, J=7.6 Hz, 1H), 6.75 (s, 1H), 3.92-3.76 (m, 6H), 3.26-3.18 (m, 4H), 2.96-2.90 (m, 1H), 2.70 (s, 3H), 2.53 (t, J=11.6 Hz, 1H), 2.29-2.22 (m, 1H), 1.91-1.82 (m, 2H), 1.79-1.69 (m, 1H), 1.55-1.44 (m, 1H). LC-MS (ESI): Rt=3.674 min, m/z 479.2 [M+H].sup.+; purity: 95.25% @ 254 nm, 97.43% @ 214 nm.

##STR00070##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-tosylpiperidin-3-yl)methanone

[0419] Except for using 4-methylbenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 20 (60 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 15.

[0420] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.02 (d, J=8.0 Hz, 1H), 7.87 (d, J=8.0 Hz, 1H), 7.69-7.63 (m, 3H), 7.52-7.46 (m, 3H), 6.92 (s, 1H), 3.79-3.71 (m, 4H), 3.66-3.61 (m, 2H), 3.20-3.14 (m, 4H), 2.97-2.92 (m, 1H), 2.59 (s, 3H), 2.42 (s, 3H), 2.30 (t, J=11.2 Hz, 1H), 2.18-2.13 (m, 1H), 1.81-1.72 (m, 2H), 1.66-1.57 (m, 1H), 1.26-1.17 (m, 1H). LC-MS (ESI): Rt=4.042 min, m/z 493.3, 3 [M+H].sup.+; purity: 99.79% @ 254 nm, 99.42% @ 214 nm.

##STR00071##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(m-tolylsulfonyl)piperidin-3-yl)methanone

[0421] Except for using 3-methylbenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 21 (40 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 15.

[0422] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.02-7.96 (m, 2H), 7.68-7.64 (m, 1H), 7.57-7.56 (m, 2H), 7.47 (t, J=7.2 Hz, 1H), 7.43-7.41 (m, 2H), 6.76 (s, 1H), 3.90-3.80 (m, 6H), 3.31-3.18 (m, 4H), 2.97-2.90 (m, 1H), 2.70 (s, 1H), 2.53 (t, J=11.6 Hz, 1H), 2.44 (s, 3H), 2.29-2.23 (m, 1H), 1.91-1.83 (m, 2H), 1.76-1.69 (m, 1H), 1.55-1.45 (m, 1H). LC-MS (ESI): Rt=4.090 min, m/z 493.2 [M+H].sup.+; purity: 99.75% @ 254 nm, 99.93% @214 nm.

##STR00072##

(1-((3,4-dimethylphenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone

[0423] Except for using 3,4-dimethylbenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 22 (60 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0424] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 8.01 (d, J=8.0 Hz, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.66 (t, J=8.0 Hz, 1H), 7.52-7.42 (m, 4H), 6.91 (s, 1H), 3.79-3.60 (m, 6H), 3.18-3.10 (m, 4H), 2.95 (t, J=11.2 Hz, 1H), 2.58 (s, 3H), 2.33-2.32 (m, 6H), 2.29-2.27 (m, 1H), 2.19-2.14 (m, 1H), 1.81-1.72 (m, 2H), 1.66-1.57 (m, 1H), 1.26-1.17 (m, 1H). LC-MS (ESI): Rt=3.953 min, m/z 507.2 [M+H].sup.+; purity: 98.99% @ 254 nm, 99.65% @214 nm.

##STR00073##

(1-(4-ethylphenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl) piperazin-1-yl)methanone

[0425] Except for using 4-ethylbenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 23 (70 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 15.

[0426] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.01-7.95 (m, 2H), 7.68-7.63 (m, 3H), 7.46 (t, J=7.2 Hz, 1H), 7.35 (d, J=8.0 Hz, 2H), 6.75 (s, 1H), 3.89-3.77 (m, 6H), 3.28-3.17 (m, 4H), 2.95-2.90 (m, 1H), 2.76-2.72 (m, 2H), 2.70 (s, 3H), 2.49 (t, J=11.6 Hz, 1H), 2.22 (t, J=11.6 Hz, 1H), 1.89-1.82 (m, 2H), 1.78-1.68 (m, 1H), 1.53-1.44 (m, 1H), 1.27 (t, J=7.6 Hz, 3H). LC-MS (ESI): Rt=2.547 min, m/z 507.3 [M+H].sup.+; purity: 98.01% @254 nm, 97.65% @ 214 nm.

##STR00074##

(1-((4-fluorophenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone

[0427] Except for using 4-fluorobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 24 (50 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 15.

[0428] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 8.02 (d, J=8.0 Hz, 1H), 7.87-7.82 (m, 3H), 7.68-7.64 (m, 1H), 7.54-7.48 (m, 3H), 6.91 (s, 1H), 3.80-3.64 (m, 6H), 3.22-3.07 (m, 4H), 3.00-2.93 (m, 1H), 2.58 (s, 3H), 2.35 (t, J=11.2 Hz, 1H), 2.24-2.18 (m, 1H), 1.82-1.73 (m, 2H), 1.66-1.57 (m, 1H), 1.30-1.18 (m, 1H). LC-MS (ESI): Rt=3.359 min, m/z 497.2 [M+H].sup.+; purity: 99.62% @ 254 nm, 99.45% @ 214 nm.

##STR00075##

(1-(4-chlorophenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl) methanone

[0429] Except for using 4-chlorobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 25 (75 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 15.

[0430] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.00 (d, J=8.4 Hz, 1H), 7.96 (d, J=7.6 Hz, 1H), 7.70 (d, J=8.4 Hz, 2H), 7.65 (t, J=7.2 Hz, 1H), 7.52 (d, J=8.4 Hz, 2H), 7.46 (t, J=8.0 Hz, 1H), 6.75 (s, 1H), 3.89-3.81 (m, 6H), 3.25-3.17 (m, 4H), 2.92-2.89 (m, 1H), 2.70 (s, 3H), 2.53 (t, J=11.2 Hz, 1H), 2.25 (td, J=12.0, 2.4 Hz, 1H), 1.92-1.88 (m, 2H), 1.75-1.72 (m, 1H), 1.51-1.47 (m, 1H). LC-MS (ESI): Rt=4.305 min, m/z 513.2 [M+H].sup.+; purity: 99.71% @ 254 nm, 99.86% @ 214 nm.

##STR00076##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(4-(trifluoromethyl)phenylsulfonyl)piperidin-3-yl)methanone

[0431] Except for using 4-(trifluoromethyl)benzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 26 (36 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 15.

[0432] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.02-7.95 (m, 2H), 7.90 (d, J=8.4 Hz, 2H), 7.81 (d, J=8.0 Hz, 2H), 7.68 (t, J=7.6 Hz, 1H), 7.46 (t, J=7.2 Hz, 1H), 6.75 (s, 1H), 3.92-3.81 (m, 6H), 3.24-3.18 (m, 4H), 2.93 (t, J=11.6 Hz, 1H), 2.70 (s, 3H), 2.56 (t, J=11.6 Hz, 1H), 2.28 (t, J=12.0 Hz, 1H), 1.94-1.85 (m, 2H), 1.71-1.70 (m, 1H), 1.51-1.48 (m, 1H). LC-MS (ESI): Rt=3.948 min, m/z 547.2 [M+H].sup.+; purity: 99.85% @ 254 nm, 99.93% @ 214 nm.

##STR00077##

(1-(3-fluorophenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone

[0433] Except for using 3-fluorobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 27 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0434] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.01-7.95 (m, 2H), 7.65 (td, J=7.2, 1.2 Hz, 1H), 7.55-7.54 (m, 2H), 7.49-7.44 (m, 2H), 7.33-7.31 (m, 1H), 6.75 (s, 1H), 3.88-3.76 (m, 6H), 3.29-3.18 (m, 4H), 2.95-2.88 (m, 1H), 2.70 (s, 3H), 2.57 (t, J=11.6 Hz, 1H), 2.31 (td, J=12.0, 2.4 Hz, 1H), 1.88 (t, J=17.2 Hz, 2H), 1.78-1.69 (m, 1H), 1.53-1.43 (m, 1H). LC-MS (ESI): Rt=3.411 min, m/z 497.2 [M+H].sup.+; purity: 98.97% @ 254 nm, 98.33% @ 214 nm.

##STR00078##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(3-nitrophenylsulfonyl)piperidin-3-yl)methanone

[0435] Except for using 3-nitrobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 28 (60 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0436] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.61 (t, J=2.0 Hz, 1H), 8.47 (dd, J=8.0, 1.2 Hz, 1H), 8.09 (d, J=7.6 Hz, 1H), 8.00 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.0 Hz, 1H),), 7.77 (d, J=8.0 Hz, 1H), 7.65 (td, J=8.0, 1.2 Hz, 1H), 7.46 (d, J=8.0 Hz, 1H), 6.75 (s, 1H), 3.95-3.79 (m, 6H), 3.27-3.18 (m, 4H), 2.94 (t, J=2.8 Hz, 1H), 2.64 (s, 3H), 2.61 (t, J=11.2 Hz, 1H), 2.36 (td, J=11.6, 2.8 Hz, 1H), 1.96-1.92 (m, 2H), 1.77-1.74 (m, 1H), 1.47-1.44 (m, 1H). LC-MS (ESI): Rt=3.455 min, m/z 524.2 [M+H].sup.+; purity: 97.76% @254 nm, 97.60% @ 214 nm.

##STR00079##

(1-(4-methoxyphenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone

[0437] Except for using 4-methoxybenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 29 (60 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 15.

[0438] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.03 (d, J=8.0 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.70 (d, J=8.8 Hz, 2H), 7.66 (t, J=8.0 Hz, 1H), 7.47 (t, J=8.0 Hz, 1H), 7.00 (t, J=11.6 Hz, 2H), 6.75 (s, 1H), 3.88-3.82 (m, 9H), 3.30-3.18 (m, 4H), 2.93 (t, J=11.2 Hz, 1H), 2.71 (s, 3H), 2.47 (t, J=11.6 Hz, 1H), 2.21 (td, J=12.0, 2.4 Hz, 1H), 1.86 (t, J=14.4 Hz, 2H), 1.78-1.72 (m, 1H), 1.52-1.45 (m, 1H). LC-MS (ESI): Rt=3.664 min, m/z 509.3 [M+H].sup.+; purity: 99.71% @ 254 nm, 99.87% @ 214 nm.

##STR00080##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(perfluorophenylsulfonyl)piperidin-3-yl)methanone

[0439] Except for using 2,3,4,5,6-pentafluorobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 30 (65 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 15.

[0440] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.01 (d, J=8.4 Hz, 1H), 7.96 (d, J=7.6 Hz, 1H), 7.65 (t, J=8.0 Hz, 1H), 7.46 (t, J=8.4 Hz, 1H), 6.75 (s, 1H), 4.03-3.98 (m, 2H), 3.88-3.80 (m, 4H), 3.29-3.19 (m, 4H), 2.98-2.88 (m, 2H), 2.73-2.67 (m, 4H), 2.01-1.98 (m, 1H), 1.94-1.90 (m, 1H), 1.81-1.65 (m, 2H). LC-MS (ESI): Rt=2.884 min, m/z 569.2 [M+H].sup.+; purity: 97.59% @ 254 nm, 98.79% @ 214 nm.

##STR00081##

(1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone

[0441] Except for using 4-(dimethylamino)benzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 31 (75 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15,

[0442] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.02-7.96 (m, 2H), 7.65 (t, J=8.4 Hz, 1H), 7.59 (d, J=9.2 Hz, 2H), 7.46 (t, J=8.0 Hz, 1H), 6.75 (s, 1H), 6.68 (d, J=8.8 Hz, 2H), 3.85-3.80 (m, 6H), 3.23-3.17 (m, 4H), 3.05 (s, 6H), 2.95-2.89 (m, 1H), 2.70 (s, 3H), 2.44 (t, J=10.4 Hz, 1H), 2.18 (t, J=11.2 Hz, 1H), 1.87-1.81 (m, 2H), 1.73-1.69 (m, 1H), 1.49-1.45 (m, 1H). LC-MS (ESI): Rt=3.160 min, m/z 522.3 [M+H].sup.+; purity: 99.81% @ 254 nm, 99.87% @ 214 nm.

##STR00082##

(1-(4-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone

[0443] Except for using 4-hydroxybenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 32 (40 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 15.

[0444] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 10.53 (br s, 1H), 8.01 (d, J=8.4 Hz, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.65 (t, J=7.2 Hz, 1H), 7.57 (d, J=8.8 Hz, 2H), 7.49 (t, J=7.2 Hz, 1H), 6.97 (d, J=8.8 Hz, 2H), 6.91 (s, 1H), 3.78-3.71 (m, 4H), 3.62-3.57 (m, 2H), 3.16-3.06 (m, 4H), 2.93 (t, J=11.2 Hz, 1H), 2.58 (s, 3H), 2.28 (t, J=11.2 Hz, 1H), 2.13 (t, J=10.8 Hz, 1H), 1.81-1.71 (m, 2H), 1.65-1.59 (m, 1H), 1.26-1.14 (m, 1H). LC-MS (ESI): Rt=3.480 min, m/z 495.2 [M+H].sup.+; purity: 98.60% @ 254 nm, 98.10% @214 nm.

##STR00083##

(1-(2-fluorophenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone

[0445] Except for using 2-fluorobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 33 (60 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15

[0446] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.00 (d, J=8.4 Hz, 1H), 7.96 (d, J=7.6 Hz, 1H), 7.85 (td, J=7.6, 1.6 Hz, 1H), 7.65 (td, J=8.4, 1.6 Hz, 1H), 7.59-7.57 (m, 1H), 7.46 (t, J=7.2 Hz, 1H), 7.30-7.26 (m, 1H), 7.22 (t, J=8.4 Hz, 1H), 6.75 (s, 1H), 3.97-3.81 (m, 6H), 3.25-3.17 (m, 4H), 2.93-2.89 (m, 1H), 2.78 (t, J=11.2 Hz, 1H), 2.69 (s, 3H), 2.58 (t, J=8.0 Hz, 1H), 1.95-1.92 (m, 1H), 1.87-1.84 (m, 1H), 1.74-1.66 (m, 2H). LC-MS (ESI): Rt=3.766 min, m/z 497.2 [M+H].sup.+; purity: 99.72% @ 254 nm, 99.86% @ 214 nm.

##STR00084##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(4-phenoxyphenylsulfonyl)piperidin-3-yl)methanone

[0447] Except for using 4-phenoxybenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 34 (65 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0448] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.00 (d, J=8.4 Hz, 1H), 7.96 (d, J=7.6 Hz, 1H), 7.71 (dd, J=6.8, 2.0 Hz, 2H), 7.65 (td, J=8.4, 1.2 Hz, 1H), 7.48-7.40 (m, 3H), 7.26-7.21 (m, 1H), 7.10-7.04 (m, 4H), 6.75 (s, 1H), 3.87-3.83 (m, 6H), 3.24-3.18 (m, 4H), 2.93 (t, J=11.2 Hz, 1H), 2.69 (s, 3H), 2.52 (t, J=11.2 Hz, 1H), 2.27 (td, J=12.0, 2.8 Hz, 1H), 1.87 (t, J=14.4 Hz, 2H), 1.76-1.72 (m, 1H), 1.53-1.49 (m, 1H). LC-MS (ESI): Rt=3.881 min, m/z 571.2 [M+H].sup.+; purity: 97.52% @ 254 nm, 97.59% @ 214 nm.

##STR00085##

4-(3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)benzonitrile

[0449] Except for using 4-cyanobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 35 (85 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0450] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.00 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.89-7.83 (m, 4H), 7.66 (td, J=7.2, 1.2 Hz, 1H), 7.46 (t, J=8.0 Hz, 1H), 6.75 (s, 1H), 3.92-3.81 (m, 6H), 3.26-3.18 (m, 4H), 2.93-2.90 (m, 1H), 2.69 (s, 3H), 2.59 (t, J=11.2 Hz, 1H), 2.30 (td, J=9.2, 2.8 Hz, 1H), 1.95-1.85 (m, 2H), 1.76-1.73 (m, 1H), 1.52-1.48 (m, 1H). LC-MS (ESI): Rt=3.490 min, m/z 504.2 [M+H].sup.+; purity: 98.75% @ 254 nm, 99.37% @ 214 nm.

##STR00086##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(4-(methylsulfonyl)phenylsulfonyl)piperidin-3-yl)methanone

[0451] Except for using 4-(methylsulfonyl)benzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 36 (50 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0452] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.13 (d, J=8.8 Hz, 2H), 8.02-7.95 (m, 4H), 7.65 (td, J=8.4, 1.2 Hz, 1H), 7.46 (t, J=8.0 Hz, 1H), 6.75 (s, 1H), 3.93-3.81 (m, 6H), 3.26-3.18 (m, 4H), 3.12 (s, 3H), 2.93-2.90 (m, 1H), 2.70 (s, 3H), 2.61 (t, J=7.6 Hz, 1H), 2.33 (td, J=8.0, 2.8 Hz, 1H), 1.95-1.86 (m, 2H), 1.76-1.74 (m, 1H), 1.52-1.48 (m, 1H). LC-MS (ESI): Rt=3.589 min, m/z 557.2 [M+H].sup.+; purity: 99.07% @ 254 nm, 99.11% @ 214 nm.

##STR00087##

methyl 4-(3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)benzoate

[0453] Except for using methyl 4-(chlorosulfonyl)benzoate instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 37 (230 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0454] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.19 (d, J=8.4 Hz, 2H), 8.10 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.84 (d, J=8.4 Hz, 2H), 7.65 (t, J=7.2 Hz, 1H), 7.46 (t, J=7.6 Hz, 1H), 6.75 (s, 1H), 3.97 (s, 3H), 3.93-3.81 (m, 6H), 3.25-3.18 (m, 4H), 2.95-2.89 (m, 1H), 2.70 (s, 3H), 2.56 (t, J=11.2 Hz, 1H), 2.28 (t, J=12.0 Hz, 1H), 1.92-1.80 (m, 2H), 1.75-1.68 (m, 1H), 1.54-1.44 (m, 1H). LC-MS (ESI): Rt=1.62 min, m/z 537.3 [M+H].sup.+; purity: 100% @ 254 nm, 87% @ 214 nm.

##STR00088##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-(4-phenylbenzenesulfonyl)piperidin-3-yl)methanone

[0455] Except for using methyl [1,1′-biphenyl]-4-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 38 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0456] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.01 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.83 (d, J=8.4 Hz, 2H), 7.73 (d, J=8.4 Hz, 2H), 7.65 (t, J=7.2 Hz, 1H), 7.60 (d, J=8.4 Hz, 2H), 7.51-7.42 (m, 4H), 6.75 (s, 1H), 3.94-3.81 (m, 6H), 3.25-3.19 (m, 4H), 2.98-2.91 (m, 1H), 2.70 (s, 3H), 2.58 (t, J=11.2 Hz, 1H), 2.32 (td, J=12.0, 2.8 Hz, 1H), 1.92-1.84 (m, 2H), 1.78-1.74 (m, 1H), 1.53-1.49 (m, 1H). LC-MS (ESI): Rt=3.630 min, m/z 555.3 [M+H].sup.+; purity: 98.67% @ 254 nm, 98.85% @ 214 nm.

##STR00089##

(1-(3-methoxyphenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone

[0457] Except for using 3-methoxybenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 39 (40 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0458] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.02-7.95 (m, 2H), 7.66 (t, J=6.8 Hz, 1H), 7.49-7.43 (m, 2H), 7.35-7.33 (m, 1H), 7.29-7.27 (m, 1H), 7.14-7.11 (m, 1H), 6.76 (s, 1H), 3.90-3.80 (m, 9H), 3.30-3.15 (m, 4H), 2.97-2.88 (m, 1H), 2.70 (s, 3H), 2.56 (t, J=11.2 Hz, 1H), 2.33-2.27 (m, 1H), 1.91-1.83 (m, 2H), 1.78-1.69 (m, 1H), 1.53-1.49 (m, 1H. LC-MS (ESI): Rt=3.82 min, m/z 509.2 [M+H].sup.+; purity: 100% @ 254 nm, 100% @ 214 nm.

##STR00090##

(1-((4-bromophenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone

[0459] Except for using 3-bromobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 40 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0460] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.03 (d, J=8.0 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.69-7.61 (m, 5H), 7.47 (t, J=8.0 Hz, 1H), 6.75 (s, 1H), 3.88-3.82 (m, 6H), 3.30-3.19 (m, 4H), 2.91 (t, J=11.2 Hz, 1H), 2.71 (s, 3H), 2.53 (t, J=11.6 Hz, 1H), 2.26 (t, J=12.0 Hz, 1H), 1.92-1.83 (m, 2H), 1.79-1.75 (m, 1H), 1.55-1.48 (m, 1H). LC-MS (ESI): Rt=3.664 min, m/z 557.1 [M+H].sup.+; purity: 99.05% @ 254 nm, 99.53% @ 214 nm.

##STR00091##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(phenylsulfonyl)piperidin-3-yl)methanone

[0461] To a solution in which (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone (100 mg, 0.29 mmol) and TEA (89 mg) in dichloromethane (3 mL) was slowly benzenesulfonyl chloride (57 mg, 0.32 mmol) diluted in dichloromethane (1 mL) at room temperature for 2 hours stir while. After the mixture was concentrated under reduced pressure, the residue was first purified using C18 chromatography using 40˜90% CH.sub.3CN (acetonitrile) aqueous solution as a developing solvent to obtain the target compound of Formula 41 (40 mg).

[0462] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 8.72 (d, J=5.2 Hz, 1H), 8.15 (dd, J=9.2, 6.4 Hz, 1H), 7.77-7.73 (m, 3H), 7.70-7.66 (m, 3H), 7.51-7.46 (m, 1H), 7.00 (d, J=5.2 Hz, 1H), 3.79-3.64 (m, 6H), 3.22-3.14 (m, 4H), 2.98-2.92 (m, 1H), 2.33 (t, J=11.2 Hz, 1H), 2.23-2.16 (m, 1H), 1.82-1.73 (m, 2H), 1.66-1.57 (m, 1H), 1.28-1.18 (m, 1H). MS (ESI): Rt=2.488 min, m/z 483.3 [M+H].sup.+; purity: 99.70% @ 254 nm, 99.63% @ 214 nm.

##STR00092##

(1-((4-fluorophenyl)sulfonyl)piperidin-3-yl)(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)methanone

[0463] Except for using 4-fluorobenzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 42 (55 mg) was obtained as a pale yellow solid in the same manner as in the preparation of the compound of Formula 41.

[0464] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 8.73 (d, J=5.2 Hz, 1H), 8.16 (dd, J=9.2, 6.8 Hz, 1H), 7.84 (dd, J=8.8, 5.6 Hz, 2H), 7.69 (dd, J=10.8, 2.4 Hz, 1H), 7.54-7.47 (m, 3H), 7.01 (d, J=5.2 Hz, 1H), 3.80-3.64 (m, 6H), 3.23-3.14 (m, 4H), 2.99-2.94 (m, 1H), 2.37-2.31 (m, 1H), 2.24-2.18 (m, 1H) 1.82-1.73 (m, 2H), 1.67-1.57 (m, 1H), 1.29-1.19 (m, 1H). LC-MS (ESI): Rt=3.720 min, m/z 501.2 [M+H].sup.+; purity: 95.73% @ 254 nm, 96.66% @ 214 nm.

##STR00093##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-((4-hydroxyphenyl)sulfonyl) piperidin-3-yl)methanone

[0465] Except for using 4-hydroxybenzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 43 (60 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 41.

[0466] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 10.56 (br s, 1H), 8.73 (d, J=5.2 Hz, 1H), 8.18-8.14 (m, 1H), 7.71-7.68 (m, 1H), 7.57 (d, J=8.8 Hz, 2H), 7.51-7.46 (m, 1H), 7.01-6.96 (m, 3H), 3.79-3.72 (m, 4H), 3.62-3.57 (m, 2H), 3.21-3.14 (m, 4H), 2.97-2.91 (m, 1H), 2.27 (t, J=11.2 Hz, 1H), 2.15-2.10 (m, 1H), 1.81-1.72 (m, 2H), 1.65-1.56 (m, 1H), 1.26-1.16 (m, 1H). LC-MS (ESI): Rt=3.827 min, m/z 499.2 [M+H].sup.+; purity: 96.36% @254 nm, 97.37% @ 214 nm.

##STR00094##

(1-((4-(dimethylamino)phenyl)sulfonyl)piperidin-3-yl)(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)methanone

[0467] Except for using 4-(dimethylamino)benzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 44 (85 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 41.

[0468] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.73 (d, J=5.2 Hz, 1H), 8.05-8.01 (m, 1H), 7.71 (dd, J=10.0, 2.8 Hz, 1H), 7.61-7.57 (m, 2H), 7.34-7.29 (m, 1H), 6.84 (d, J=5.2 Hz, 1H), 6.70-6.66 (m, 2H), 3.88-3.80 (m, 6H), 3.27-3.18 (m, 4H), 3.05 (s, 6H), 2.96-2.89 (m, 1H), 2.45 (t, J=11.2 Hz, 1H), 2.23-2.17 (m, 1H), 1.87-1.81 (m, 2H), 1.74-1.71 (m, 1H), 1.53-1.42 (m, 1H). LC-MS (ESI): Rt=3.361 min, m/z 526.3 [M+H].sup.+; purity: 97.03% @ 254 nm, 97.58% @ 214 nm.

##STR00095##

N-(4-(3-(1-(7-fluoroquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)phenyl) acetamide

[0469] Except for using 4-acetamidobenzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 45 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 41.

[0470] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.8 Hz, 1H), 8.02 (dd, J=9.6, 6.4 Hz, 1H), 7.73-7.70 (m, 6H), 7.31 (td, J=12.0, 2.8 Hz, 1H), 6.84 (d, J=4.8 Hz, 1H), 3.88-3.82 (m, 6H), 3.26-3.18 (m, 4H), 2.90 (t, J=6.8 Hz, 1H), 2.50 (t, J=11.2 Hz, 1H), 2.27-2.24 (m, 1H), 2.22 (s, 3H), 1.86 (t, J=14.4 Hz, 2H), 1.73-1.65 (m, 1H), 1.49-1.45 (m, 1H). LC-MS (ESI): Rt=3.762 min, m/z 540.3 [M+H].sup.+; purity: 96.47% @ 254 nm, 97.20% @ 214 nm.

##STR00096##

(R)—N-(4-(3-(1-(7-fluoroquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)phenyl)acetamide

[0471] Except for using (R)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone instead of (4-(7-Fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone, Formula 46 (50 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 45.

[0472] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 10.38 (s, 1H), 8.72 (d, J=5.2 Hz, 1H), 8.17-8.13 (m, 1H), 7.83 (d, J=8.8 Hz, 2H), 7.70-7.67 (m, 3H), 7.48 (td, J=8.8, 2.8 Hz, 1H), 7.00 (d, J=4.8 Hz, 1H), 3.78-3.71 (m, 4H), 3.64-3.59 (m, 2H), 3.20-3.14 (m, 4H), 2.92 (t, J=10.8 Hz, 1H), 2.31 (t, J=10.8 Hz, 1H), 2.18 (t, J=12.0 Hz, 1H), 2.09 (s, 3H), 1.80-1.72 (m, 2H), 1.65-1.56 (m, 1H), 1.27-1.17 (m, 1H). LC-MS (ESI): Rt=3.444 min, m/z 540.2 [M+H].sup.+; purity: 96.39% @ 254 nm, 96.69% @ 214 nm.

[0473] chiral HPLC: Column: Chiralpak IB 5 um 4.6×250 mm; Mobile Phase: Hex EtOH:DEA=50:50:0.2 at 1 mL/min; Temp: 30° C.; Wavelength: 254 nm, Rt=11.232 min, 99.51% ee.

##STR00097##

(S)—N-(4-(3-(1-(7-fluoroquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)phenyl)acetamide

[0474] Except for using (S)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone instead of (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone, Formula 47 (60 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 45.

[0475] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 10.39 (s, 1H), 8.72 (d, J=4.8 Hz, 1H), 8.17-8.13 (m, 1H), 7.83 (d, J=9.2 Hz, 2H), 7.70-7.67 (m, 3H), 7.46 (td, J=17.2, 2.8 Hz, 1H), 7.00 (d, J=4.8 Hz, 1H), 3.78-3.71 (m, 4H), 3.64-3.59 (m, 2H), 3.20-3.13 (m, 4H), 2.95-2.90 (m, 1H), 2.30 (t, J=11.6 Hz, 1H), 2.18 (t, J=9.2 Hz, 1H), 2.09 (s, 3H), 1.80-1.72 (m, 2H), 1.65-1.56 (m, 1H), 1.27-1.17 (m, 1H). LC-MS (ESI): Rt=3.431 min, m/z 540.2 [M+H].sup.+; purity: 95.66% @ 254 nm, 96.62% @ 214 nm.

[0476] chiral HPLC: Column: Chiralpak IB 5 um 4.6×250 mm; Mobile Phase: Hex EtOH:DEA=50:50:0.2 at 1 mL/min; Temp: 30° C.; Wavelength: 254 nm, Rt=8.276 min, 99.32% ee.

##STR00098##

(R)-(1-((4-(dimethylamino)phenyl)sulfonyl)piperidin-3-yl)(4-(quinolin-4-yl) piperazin-1-yl)methanone

[0477] Except for using (R)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone instead of (4-(7-Fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone, Formula 48 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 44.

[0478] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=5.2 Hz, 1H), 8.05-8.01 (m, 1H), 7.76-7.73 (m, 1H), 7.59 (d, J=8.8 Hz, 2H), 7.34-7.30 (m, 1H), 6.85 (d, J=4.8 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 3.88-3.80 (m, 6H), 3.31-3.21 (m, 4H), 3.05 (s, 6H), 2.95-2.88 (m, 1H), 2.45 (t, J=11.2 Hz, 1H), 2.24-2.18 (m, 1H), 1.87-1.80 (m, 2H), 1.76-1.71 (m, 1H), 1.54-1.46 (m, 1H). LC-MS (ESI): Rt=3.805 min, m/z 526.2 [M+H].sup.+; purity: 96.16% @254 nm, 96.82% @ 214 nm.

[0479] chiral HPLC: Column: Chiralpak IA 5 um 4.6×250 mm; Mobile Phase: Hex EtOH:DEA=30:70:0.2 at 1 mL/min; Temp: 30° C.; Wavelength: 230 nm, Rt=19.532 min, 99.34% ee.

##STR00099##

(S)-(1-((4-(dimethylamino)phenyl)sulfonyl)piperidin-3-yl)(4-(quinolin-4-yl) piperazin-1-yl)methanone

[0480] Except for using (S)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone instead of (4-(7-Fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone, Formula 49 (25 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 44.

[0481] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=4.8 Hz, 1H), 8.05-8.01 (m, 1H), 7.73-7.70 (m, 1H), 7.59 (d, J=9.2 Hz, 2H), 7.34-7.29 (m, 1H), 6.84 (d, J=5.2 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 3.88-3.80 (m, 6H), 3.27-3.19 (m, 4H), 3.05 (s, 6H), 2.94-2.88 (m, 1H), 2.45 (t, J=11.2 Hz, 1H), 2.24-2.18 (m, 1H), 1.87-1.80 (m, 2H), 1.74-1.71 (m, 1H), 1.50-1.46 (m, 1H). LC-MS (ESI): Rt=2.928 min., m/z 526.3 [M+H].sup.+; purity: 98.15% @254 nm, 99.66% @ 214 nm.

[0482] chiral HPLC: Column: Chiralpak IA 5 um 4.6×250 mm; Mobile Phase: Hex EtOH:DEA=30:70:0.2 at 1 mL/min; Temp: 30° C.; Wavelength: 230 nm, Rt=13.264 min, 97.81% ee.

##STR00100##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-nitrophenylsulfonyl) piperidin-3-yl)methanone

[0483] Except for using 4-nitrobenzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 50 (45 mg) was obtained as a pale yellow solid in the same manner as in the preparation of the compound of Formula 41.

[0484] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=4.0 Hz, 1H), 8.39 (d, J=8.8 Hz, 2H), 8.04-8.01 (m, 1H), 7.95 (d, J=8.4 Hz, 2H), 7.73-7.70 (m, 1H), 7.34-7.29 (m, 1H), 6.84 (d, J=5.2 Hz, 1H), 3.95-3.83 (m, 6H), 3.30-3.09 (m, 4H), 2.99-2.89 (m, 1H), 2.61 (t, J=11.6 Hz, 1H), 2.35-2.29 (m, 1H), 1.92-1.87 (m, 2H), 1.78-1.75 (m, 1H), 1.56-1.49 (m, 1H). LC-MS (ESI): Rt=4.270 min, m/z 528.2 [M+H].sup.+; purity: 92.90% @ 254 nm, 92.33% @ 214 nm.

##STR00101##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-nitrophenylsulfonyl) piperidin-3-yl)methanone

[0485] Except for using 3-nitrobenzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 51 (43 mg) was obtained as a pale yellow solid in the same manner as in the preparation of the compound of Formula 41.

[0486] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=5.2 Hz, 1H), 8.61-8.60 (m, 1H), 8.49-8.46 (m, 1H), 8.09 (d, J=8.0 Hz, 1H), 8.05-8.01 (m, 1H), 7.78 (t, J=8.0 Hz, 1H), 7.73-7.70 (m, 1H), 7.34-7.29 (m, 1H), 6.85 (d, J=5.2 Hz, 1H), 3.95-3.84 (m, 6H), 3.33-3.20 (m, 4H), 2.98-2.90 (m, 1H), 2.61 (t, J=11.6 Hz, 1H), 2.40-2.34 (m, 1H), 1.95-1.88 (m, 2H), 1.82-1.71 (m, 1H), 1.55-1.48 (m, 1H). LC-MS (ESI): Rt=4.026 min, m/z 528.2 [M+H].sup.+; purity: 94.16% @ 254 nm, 95.76% @ 214 nm.

##STR00102##

(1-(4-(diethylamino)phenylsulfonyl)piperidin-3-yl)(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)methanone

[0487] Except for using 4-(diedylamino)benzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 52 (55 mg) was obtained as a pale yellow solid in the same manner as in the preparation of the compound of Formula 41

[0488] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.8 Hz, 1H), 8.05-8.01 (m, 1H), 7.73-7.70 (m, 1H), 7.54 (d, J=8.8 Hz, 2H), 7.34-7.29 (m, 1H), 6.84 (d, J=4.8 Hz, 1H), 6.63 (d, J=9.2 Hz, 2H), 3.88-3.80 (m, 6H), 3.40 (q, J=7.2 Hz, 4H), 3.27-3.19 (m, 4H), 2.98-2.87 (m, 1H), 2.47 (t, J=11.2 Hz, 1H), 2.24-2.21 (m, 1H), 1.87-1.81 (m, 2H), 1.77-1.71 (m, 1H), 1.54-1.49 (m, 1H), 1.20 (t, J=7.2 Hz, 6H). LC-MS (ESI): Rt=4.211 min, m/z 554.3 [M+H].sup.+; purity: 93.62% @ 254 nm, 93.98% @ 214 nm.

##STR00103##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-methoxyphenylsulfonyl) piperidin-3-yl)methanone

[0489] Except for using 4-methoxybenzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 53 (50 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 41,

[0490] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=4.8 Hz, 1H), 8.05-8.01 (m, 1H), 7.73-7.69 (m, 3H), 7.34-7.29 (m, 1H), 7.00 (d, J=5.2 Hz, 2H), 6.84 (d, J=5.2 Hz, 1H), 3.88-3.82 (m, 9H), 3.27-3.19 (m, 4H), 2.96-2.88 (m, 1H), 2.48 (t, J=11.6 Hz, 1H), 2.26-2.19 (m, 1H), 1.89-1.82 (m, 2H), 1.77-1.72 (m, 1H), 1.50-1.47 (m, 1H). LC-MS (ESI): Rt=3.886 min, m/z 513.2 [M+H].sup.+; purity: 97.96% @ 254 nm, 97.38% @ 214 nm.

##STR00104##

1-(4-(3-(1-(7-fluoroquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)phenyl)ethanone

[0491] Except for using 4-acetylbenzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 54 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 41.

[0492] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=4.8 Hz, 1H), 8.10 (d, J=8.4 Hz, 2H), 8.05-8.01 (m, 1H), 7.86 (d, J=8.8 Hz, 2H), 7.73-7.70 (m, 1H), 7.34-7.29 (m, 1H), 6.84 (d, J=4.8 Hz, 1H), 3.92-3.78 (m, 6H), 3.27-3.19 (m, 4H), 2.96-2.89 (m, 1H), 2.67 (s, 3H), 2.55 (t, J=11.6 Hz, 1H), 2.31-2.25 (m, 1H), 1.93-1.85 (m, 2H), 1.76-1.70 (m, 1H), 1.51-1.45 (m, 1H). LC-MS (ESI): Rt=3.841 min, m/z 525.2 [M+H].sup.+; purity: 98.02% @ 254 nm, 98.99% @ 214 nm.

##STR00105##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-phenylbenzenesulfonyl) piperidin-3-yl)methanone

[0493] Except for using [1,1′-biphenyl]-4-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 55 (56 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 41.

[0494] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=4.8 Hz, 1H), 8.05-8.01 (m, 1H), 7.84-7.82 (m, 2H), 7.75-7.70 (m, 3H), 7.62-7.60 (m, 2H), 7.51-7.41 (m, 3H), 7.34-7.29 (m, 1H), 6.84 (d, J=4.8 Hz, 1H), 3.95-3.83 (m, 6H), 3.32-3.20 (m, 4H), 2.98-2.89 (m, 1H), 2.58 (t, J=11.2 Hz, 1H), 2.37-2.28 (m, 1H), 1.92-1.85 (m, 2H), 1.81-1.71 (m, 1H), 1.53-1.48 (m, 1H). LC-MS (ESI): Rt=3.223 min, m/z 559.2 [M+H].sup.+; purity: 98.80% @254 nm, 99.17% @ 214 nm.

##STR00106##

(1-(4-bromophenylsulfonyl)piperidin-3-yl)(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)methanone

[0495] Except for using 4-bromobenzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 56 (240 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 55.

[0496] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=4.8 Hz, 1H), 8.04-8.01 (m, 1H), 7.73-7.62 (m, 5H), 7.34-7.29 (m, 1H), 6.84 (d, J=4.8 Hz, 1H), 3.89-3.82 (m, 6H), 3.31-3.19 (m, 4H), 2.95-2.88 (m, 1H), 2.54 (t, J=11.2 Hz, 1H), 2.30-2.23 (m, 1H), 1.92-1.84 (m, 2H), 1.79-1.69 (m, 1H), 1.51-1.48 (m, 1H). LC-MS (ESI): Rt=3.853 min, m/z 561.1 [M+H].sup.+; purity: 97.13% @ 254 nm, 97.17% @ 214 nm.

##STR00107##

(R)-(1-(4-bromophenylsulfonyl)piperidin-3-yl)(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)methanone

[0497] Except for using (R)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone instead of (4-(7-Fluoroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone, Formula 57 (250 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 56.

[0498] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.8 Hz, 1H), 8.04-8.01 (m, 1H), 7.73-7.62 (m, 5H), 7.34-7.29 (m, 1H), 6.84 (d, J=5.2 Hz, 1H), 3.89-3.82 (m, 6H), 3.29-3.19 (m, 4H), 2.95-2.89 (m, 1H), 2.54 (t, J=11.6 Hz, 1H), 2.29-2.23 (m, 1H), 1.92-1.84 (m, 2H), 1.79-1.72 (m, 1H), 1.54-1.46 (m, 1H). LC-MS (ESI): Rt=3.784 min, m/z 561.1 [M+H].sup.+; purity: 98.04% @ 254 nm, 98.84% @ 214 nm.

[0499] chiral HPLC: Column: Chiralpak IB 5 um 4.6×250 mm; Mobile Phase: Hex EtOH=50:50 at 1 mL/min; Temp: 30° C.; Wavelength: 254 nm, Rt=12.740 min, 99.09% ee.

##STR00108##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-methoxyphenylsulfonyl)piperidin-3-yl)methanone

[0500] Except for using 3-methoxybenzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 59 (60 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 39.

[0501] Rt=3.877 min, m/z 513.2 [M+H].sup.+; purity: 97.65% @ 254 nm, 97.42% @ 214 nm.

##STR00109##

(R)—N-(3-(3-(1-(7-fluoroquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)phenyl)acetamide

[0502] Except for using 3-acetamidobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 59 (45 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 46.

[0503] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.8 Hz, 1H), 8.05-8.01 (m, 1H), 7.89-7.88 (m, 1H), 7.83 (s, 1H), 7.72-7.69 (m, 1H), 7.60 (s, 1H), 7.50-7.48 (m, 2H), 7.34-7.29 (m, 1H), 6.85 (d, J=4.8 Hz, 1H), 3.90-3.84 (m, 6H), 3.27-3.18 (m, 4H), 2.94-2.88 (m, 1H), 2.57 (t, J=11.2 Hz, 1H), 2.36-2.29 (m, 1H), 2.21 (s, 3H), 1.91-1.82 (m, 2H), 1.74-1.69 (m, 1H), 1.54-1.48 (m, 1H). LC-MS (ESI): Rt=3.582 min, m/z 540.2 [M+H].sup.+; purity: 99.32% @ 254 nm, 99.50% @ 214 nm.

[0504] Chiral HPLC: Column: Chiralpak IG 5 um 4.6×250 mm; Mobile Phase: Hex:EtOH=40:60 at 1 mL/min; Temp: 30° C.; Wavelength: 254 nm, Rt=22.440 min, 99.43% ee.

##STR00110##

(R)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-nitrophenylsulfonyl)piperidin-3-yl)methanone

[0505] Except for using 3-nitrobenzene-1-sulfonyl chloride instead of 4-nitrobenzene-1-sulfonyl chloride, Formula 60 (170 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 46.

[0506] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=5.2 Hz, 1H), 8.62-8.61 (m, 1H), 8.49-8.46 (m, 1H), 8.11-8.09 (m, 1H), 8.05-8.01 (m, 1H), 7.78 (t, J=8.0 Hz, 1H), 7.73-7.70 (m, 1H), 7.34-7.29 (m, 1H), 6.85 (d, J=5.2 Hz, 1H), 3.95-3.84 (m, 6H), 3.32-3.20 (m, 4H), 2.98-2.91 (m, 1H), 2.61 (t, J=11.2 Hz, 1H), 2.40-2.34 (m, 1H), 1.95-1.88 (m, 2H), 1.81-1.70 (m, 1H), 1.57-1.49 (m, 1H). LC-MS (ESI): Rt=3.315 min, m/z 528.2 [M+H].sup.+; purity: 96.67% @ 254 nm, 97.00% @ 214 nm.

##STR00111##

(R)-(1-(3-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)methanone

[0507] Except for using 3-(dimethylamino)benzene-1-sulfonyl chloride instead of 4-(dimethylamino)benzene-1-sulfonyl chloride, Formula 61 (20 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 48.

[0508] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.76 (d, J=4.8 Hz, 1H), 8.05-8.01 (m, 1H), 7.72-7.69 (m, 1H), 7.37-7.29 (m, 2H), 7.05-7.00 (m, 2H), 6.88-6.83 (m, 2H), 3.89-3.75 (m, 6H), 3.29-3.18 (m, 4H), 3.01 (s, 6H), 2.94-2.87 (m, 1H), 2.56 (t, J=10.8 Hz, 1H), 2.35-2.28 (m, 1H), 1.90-1.82 (m, 2H), 1.78-1.70 (m, 1H), 1.56-1.46 (m, 1H). LC-MS (ESI): Rt=3.737 min, m/z 526.2 [M+H].sup.+; purity: 98.59% @ 254 nm, 98.90% @ 214 nm.

##STR00112##

(1-(3-bromophenylsulfonyl)piperidin-3-yl)(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)methanone

[0509] Except for using 3-bromobenzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 62 (470 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 55.

[0510] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.79-8.77 (m, 1H), 8.05-8.01 (m, 1H), 7.93-7.89 (m, 1H), 7.75-7.69 (m, 3H), 7.43 (t, J=8.0 Hz, 1H), 7.34-7.29 (m, 1H), 6.85 (d, J=5.2 Hz, 1H), 3.89-3.80 (m, 6H), 3.33-3.20 (m, 4H), 2.95-2.89 (m, 1H), 2.59 (t, J=10.8 Hz, 1H), 2.37-2.30 (m, 1H), 1.93-1.85 (m, 2H), 1.79-1.72 (m, 1H), 1.58-1.51 (m, 1H). LC-MS (ESI): Rt=3.711 min, m/z 561.1 [M+H].sup.+; purity: 97.20% @ 254 nm, 97.94% @214 nm.

##STR00113##

N-(4-(3-(1-(2-(trifluoromethyl)quinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)phenyl)acetamide

[0511] Except for using piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone instead of (4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone, Formula 63 (60 mg) was obtained as a white solid in the same manner as in the preparation method of the compound of Formula 15.

[0512] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.20 (d, J=8.4 Hz, 1H), 8.05 (d, J=8.4 Hz, 1H), 7.78 (td, J=7.2, 1.2 Hz, 1H), 7.73-7.67 (m, 4H), 7.64 (t, J=7.2 Hz, 1H), 7.57 (s, 1H), 7.16 (s, 1H), 3.93-3.85 (m, 6H), 3.36-3.27 (m, 4H), 2.91-2.88 (m, 1H), 2.51 (t, J=11.2 Hz, 1H), 2.29-2.25 (m, 1H), 2.22 (s, 3H), 1.87 (t, J=16.8 Hz, 2H), 1.75-1.71 (m, 1H), 1.54-1.46 (m, 1H). LC-MS (ESI): Rt=3.953 min, m/z 590.2 [M+H].sup.+; purity: 99.95% @254 nm, 99.88% @ 214 nm.

##STR00114##

(1-(phenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

[0513] Except for using benzenesulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 64 (65 mg) was obtained as a white solid in the same manner as in the preparation method of the compound of Formula 63.

[0514] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.20 (d, J=8.4 Hz, 1H), 8.05 (d, J=8.4 Hz, 1H), 7.80-7.76 (m, 3H), 7.64 (dd, J=7.2, 1.2 Hz, 2H), 7.56-7.52 (m, 2H), 7.16 (s, 1H), 3.92-3.85 (m, 6H), 3.37-3.27 (m, 4H), 2.93-2.90 (m, 1H), 2.52 (t, J=11.2 Hz, 1H), 2.26 (td, J=9.6, 2.8 Hz, 1H), 1.87 (t, J=16.8 Hz, 2H), 1.75-1.72 (m, 1H), 1.54-1.46 (m, 1H). LC-MS (ESI): Rt=3.585 min, m/z 533.2 [M+H].sup.+; purity: 99.35% @ 254 nm, 99.87% @214 nm.

##STR00115##

(1-tosylpiperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

[0515] Except for using 4-methylbenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 65 (60 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 63.

[0516] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.20 (d, J=8.8 Hz, 1H), 8.05 (d, J=8.0 Hz, 1H), 7.78 (td, J=8.4, 1.6 Hz, 1H), 7.66-7.62 (m, 3H), 7.33 (d, J=8.0 Hz, 2H), 7.15 (s, 1H), 3.93-3.85 (m, 6H), 3.36-3.27 (m, 4H), 2.92-2.89 (m, 1H), 2.49 (t, J=11.6 Hz, 1H), 2.44 (s, 3H), 2.23 (td, J=9.2, 2.8 Hz, 1H), 1.86 (t, J=16.4 Hz, 2H), 1.75-1.71 (m, 1H), 1.51-1.47 (m, 1H). LC-MS (ESI): Rt=4.039 min, m/z 547.2 [M+H].sup.+; purity: 99.62% @254 nm, 99.65% @ 214 nm.

##STR00116##

(1-(4-fluorophenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

[0517] Except for using 4-fluorobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 65 (70 mg) was obtained as a white solid in the same manner as in the method for preparing compound of Formula 63.

[0518] .sup.1HNMR (400 MHz, CDCl.sub.3): δ 8.20 (d, J=8.4 Hz, 1H), 8.05 (d, J=8.0 Hz, 1H), 7.80-7.76 (m, 3H), 7.64 (t, J=7.2 Hz, 1H), 7.22 (d, J=8.8 Hz, 2H), 7.16 (s, 1H), 3.93-3.85 (m, 6H), 3.37-3.27 (m, 4H), 2.93-2.90 (m, 1H), 2.53 (t, J=11.6 Hz, 1H), 2.26 (td, J=12.0, 2.8 Hz, 1H), 1.88 (t, J=16.8 Hz, 2H), 1.77-1.73 (m, 1H), 1.52-1.48 (m, 1H). LC-MS (ESI): Rt=3.699 min, m/z 551.2 [M+H].sup.+; purity: 99.51% @ 254 nm, 99.57% @ 214 nm.

##STR00117##

(1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

[0519] Except for using 4-(dimethylamino)benzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 67 (70 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 63.

[0520] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.20 (d, J=8.4 Hz, 1H), 8.05 (d, J=7.6 Hz, 1H), 7.78 (t, J=8.8 Hz, 1H), 7.64 (t, J=8.0 Hz, 1H), 7.59 (t, J=8.8 Hz, 2H), 7.15 (s, 1H), 6.68 (d, J=8.8 Hz, 2H), 3.93-3.80 (m, 6H), 3.38-3.26 (m, 4H), 3.05 (s, 6H), 2.95-2.88 (m, 1H), 2.45 (t, J=11.6 Hz, 1H), 2.21 (td, J=12.4, 2.4 Hz, 1H), 1.88-1.80 (m, 2H), 1.77-1.67 (m, 1H), 1.53-1.43 (m, 1H). LC-MS (ESI): Rt=3.825 min, m/z 576.3 [M+H].sup.+; purity: 98.55% @ 254 nm, 99.53% @ 214 nm.

##STR00118##

(1-(4-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl) quinolin-4-yl)piperazin-1-yl)methanone

[0521] Except for using 4-hydroxybenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 68 (58 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 63.

[0522] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 10.54 (s, 1H), 8.16 (d, J=8.0 Hz, 1H), 8.09 (d, J=8.0 Hz, 1H), 7.86 (t, J=8.0 Hz, 1H), 7.72 (t, J=7.2 Hz, 1H), 7.57 (t, J=8.8 Hz, 2H), 7.29 (s, 1H), 6.97 (d, J=8.8 Hz, 2H), 3.81-3.74 (m, 4H), 3.62-3.57 (m, 2H), 3.32-3.21 (m, 4H), 2.94 (t, J=11.2 Hz, 1H), 2.27 (t, J=10.8 Hz, 1H), 2.12 (t, J=11.6 Hz, 1H), 1.82-1.72 (m, 2H), 1.65-1.55 (m, 1H), 1.26-117 (m, 1H). LC-MS (ESI): Rt=3.614 min, m/z 549.2 [M+H].sup.+; purity: 99.76% @ 254 nm, 99.77% @ 214 nm.

##STR00119##

(R)-(1-(4-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl) quinolin-4-yl)piperazin-1-yl)methanone

[0523] Except for using (R)-piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone instead of piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, Formula 69 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 68.

[0524] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 10.54 (br s, 1H), 8.16 (d, J=8.0 Hz, 1H), 8.09 (d, J=8.0 Hz, 1H), 7.86 (t, J=8.0 Hz, 1H), 7.72 (t, J=7.2 Hz, 1H), 7.57 (t, J=8.8 Hz, 2H), 7.29 (s, 1H), 6.97 (d, J=8.8 Hz, 2H), 3.81-3.74 (m, 4H), 3.62-3.57 (m, 2H), 3.32-3.21 (m, 4H), 2.94 (t, J=11.2 Hz, 1H), 2.27 (t, J=10.8 Hz, 1H), 2.12 (t, J=11.6 Hz, 1H), 1.82-1.72 (m, 2H), 1.65-1.55 (m, 1H), 1.26-117 (m, 1H). LC-MS (ESI): Rt=4.086 min., m/z 549.2 [M+H].sup.+; purity: 98.91% @ 254 nm, 99.74% @ 214 nm.

[0525] chiral HPLC: Column: Chiralpak IA 5 um 4.6×250 mm; Mobile Phase: Hex EtOH=70:30 at 1 mL/min; Temp: 30° C.; Wavelength: 254 nm, Rt=8.171 min, 98.96% ee.

##STR00120##

(S)-(1-(4-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl) quinolin-4-yl)piperazin-1-yl)methanone

[0526] Except for using (S)-piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone instead of Piperidin-3-yl(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone, Formula 70 (80 mg) was obtained as a white solid in the same manner as in the preparation method of the compound of Formula 68.

[0527] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 10.54 (brs, 1H), 8.16 (d, J=8.0 Hz, 1H), 8.09 (d, J=8.0 Hz, 1H), 7.86 (t, J=8.0 Hz, 1H), 7.72 (t, J=7.2 Hz, 1H), 7.57 (t, J=8.8 Hz, 2H), 7.29 (s, 1H), 6.97 (d, J=8.8 Hz, 2H), 3.81-3.74 (m, 4H), 3.62-3.57 (m, 2H), 3.32-3.21 (m, 4H), 2.94 (t, J=11.2 Hz, 1H), 2.27 (t, J=10.8 Hz, 1H), 2.12 (t, J=11.6 Hz, 1H), 1.82-1.72 (m, 2H), 1.65-1.55 (m, 1H), 1.26-117 (m, 1H). LC-MS (ESI): Rt=4.087 min, m/z 549.2 [M+H].sup.+; purity: 99.19% @ 254 nm, 99.70% @ 214 nm.

[0528] chiral HPLC: Column: Chiralpak IA 5 um 4.6×250 mm; Mobile Phase: Hex:EtOH=70:30 at 1 mL/min; Temp: 30° C.; Wavelength: 254 nm, Rt=11.178 min, 99.24% ee.

##STR00121##

(1-(4-(trifluoromethyl)phenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

[0529] Except for using 4-(trifluoromethyl)benzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 71 (80 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 63.

[0530] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.17 (d, J=8.4 Hz, 1H), 8.11-8.05 (m, 3H), 7.98 (d, J=8.0 Hz, 1H), 7.86 (t, J=7.6 Hz, 1H), 7.73 (t, J=7.2 Hz, 1H), 7.29 (s, 1H), 3.82-3.68 (m, 6H), 3.40-3.34 (m, 2H), 3.30-3.23 (m, 2H), 2.99-2.94 (m, 1H), 2.43 (t, J=11.2 Hz, 1H), 2.30 (t, J=11.6 Hz, 2H), 1.84-1.73 (m, 2H), 1.68-1.62 (m, 1H), 1.33-1.23 (m, 1H). LC-MS (ESI): Rt=3.908 min, m/z 601.2 [M+H].sup.+; purity: 98.95% @ 254 nm, 99.27% @ 214 nm.

##STR00122##

(1-(3-fluorophenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanone

[0531] Except for using 3-fluorobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 72 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 63.

[0532] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.20 (d, J=8.0 Hz, 1H), 8.05 (d, J=8.0 Hz, 1H), 7.78 (t, J=8.0 Hz, 1H), 7.64 (t, J=8.0 Hz, 1H), 7.57-7.53 (m, 2H), 7.48 (d, J=8.0 Hz, 1H), 7.34-7.30 (m, 1H), 7.16 (s, 1H), 3.94-3.85 (m, 6H), 3.37-3.28 (m, 4H), 2.93-2.90 (m, 1H), 2.57 (t, J=11.6 Hz, 1H), 2.31 (td, J=12.0, 2.4 Hz, 2H), 1.89 (t, J=16.0 Hz, 1H), 1.76-1.73 (m, 1H), 1.54-1.50 (m, 1H). LC-MS (ESI): Rt=4.094 min, m/z 551.2 [M+H].sup.+; purity: 99.24% @ 254 nm, 99.61% @ 214 nm.

##STR00123##

(1-(perfluorophenylsulfonyl)piperidin-3-yl)(4-(2-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)methanon

[0533] Except for using 2,3,4,5,6-pentafluorobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 73 (80 mg) was obtained as a white solid in the same manner as in the preparation method of the compound of Formula 63.

[0534] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.20 (d, J=8.0 Hz, 1H), 8.05 (d, J=8.4 Hz, 1H), 1H), 7.79 (td, J=7.2, 1.2 Hz, 1H), 7.64 (td, J=7.2, 1.2 Hz, 1H), 7.16 (s, 1H), 4.03-3.86 (m, 6H), 3.37-3.28 (m, 4H), 2.95-2.92 (m, 2H), 2.70 (t, J=12.0 Hz, 1H), 2.02-1.91 (m, 2H), 1.78-1.69 (m, 2H). LC-MS (ESI): Rt=4.091 min, m/z 623.2 [M+H].sup.+; purity: 98.56% @ 254 nm, 99.48% @ 214 nm.

##STR00124##

(1-(phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl) methanone

[0535] Except for using piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone instead of (4-(7-Chloroquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone, Formula 74 (60 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0536] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=4.8 Hz, 1H), 8.10 (d, J=8.4 Hz, 1H), 8.03 (d, J=8.4 Hz, 1H), 7.78-7.76 (m, 2H), 7.72-7.70 (m, 1H), 7.63-7.60 (m, 1H), 7.56-7.52 (m, 3H), 6.87 (d, J=4.8 Hz, 1H), 3.91-3.84 (m, 6H), 3.29-3.21 (m, 4H), 2.96-2.90 (m, 1H), 2.53 (t, J=11.2 Hz, 1H), 2.26 (td, J=12.0, 2.8 Hz, 1H), 1.91-1.83 (m, 2H), 1.79-1.72 (m, 1H), 1.55-1.48 (m, 1H). LC-MS (ESI): Rt=3.559 min, m/z 465.2 [M+H].sup.+; purity: 99.70% @ 254 nm, 99.13% @ 214 nm.

##STR00125##

(1-(4-fluorophenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl) methanone

[0537] Except for using 4-fluorobenzene-1-sulfonyl-chloride instead of benzenesulfonyl chloride, Formula 75 (55 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 74.

[0538] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=4.8 Hz, 1H), 8.11 (d, J=8.4 Hz, 1H), 8.02 (d, J=8.4 Hz, 1H), 7.80-7.77 (m, 2H), 7.73-7.69 (m, 1H), 7.56-7.52 (m, 1H), 7.25-7.20 (m, 2H), 6.87 (d, J=4.8 Hz, 1H), 3.90-3.84 (m, 6H), 3.30-3.22 (m, 4H), 2.96-2.90 (m, 1H), 2.53 (t, J=11.2 Hz, 1H), 2.25 (td, J=12.0, 2.8 Hz, 1H), 1.92-1.84 (m, 3H), 1.55-1.44 (m, 1H). LC-MS (ESI): Rt=3.726 min, m/z 483.2 [M+H].sup.+; purity: 99.23% @254 nm, 98.58% @ 214 nm.

##STR00126##

(1-((4-hydroxyphenyl)sulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0539] Except for using 4-hydroxybenzene-1-sulfonyl-chloride instead of benzenesulfonyl chloride, Formula 76 (52 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 74.

[0540] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 10.54 (s, 1H), 8.71 (d, J=4.4 Hz, 1H), 8.08 (d, J=8.0 Hz, 1H), 7.97 (d, J=8.0 Hz, 1H), 7.72 (t, J=7.6 Hz, 1H), 7.58-7.56 (m, 3H), 7.01-6.97 (m, 3H), 3.80-3.74 (m, 4H), 3.60-3.58 (m, 2H), 3.19-3.13 (m, 4H), 2.96-2.91 (m, 1H), 2.28 (t, J=11.2 Hz, 1H), 2.17-2.11 (m, 1H), 1.81-1.72 (m, 2H), 1.65-1.59 (m, 1H), 1.27-1.80 (m, 1H). LC-MS (ESI): Rt=3.316 min, m/z 481.2 [M+H].sup.+; purity: 95.16% @ 254 nm, 95.01% @ 214 nm.

##STR00127##

(1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0541] Except for using 4-(dimethylamino)benzene-1-sulfonyl-chloride instead of benzenesulfonyl chloride, Formula 77 (60 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 74.

[0542] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=5.2 Hz, 1H), 8.09 (d, J=8.4 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 7.70 (t, J=7.6 Hz, 1H), 7.59 (d, J=9.2 Hz, 2H), 7.54 (t, J=8.0 Hz, 1H), 6.87 (d, J=5.2 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 3.89-3.81 (m, 6H), 3.27-3.20 (m, 4H), 3.05 (s, 6H), 2.92 (t, J=11.2 Hz, 1H), 2.45 (t, J=11.2 Hz, 1H), 2.21 (t, J=11.6 Hz, 1H), 1.88-1.81 (m, 2H), 1.76-1.73 (m, 1H), 1.52-1.42 (m, 1H). LC-MS (ESI): Rt=2.971 min, m/z 508.3 [M+H].sup.+; purity: 98.74% @ 254 nm, 98.82% @ 214 nm.

##STR00128##

N-(4-((3-(4-(quinolin-4-yl)piperazine-1-carbonyl)piperidin-1-yl)sulfonyl)phenyl)acetamide

[0543] Except for using 4-acetamidobenzene-1-sulfonyl-chloride instead of benzenesulfonyl chloride, Formula 78 (50 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 74.

[0544] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77 (d, J=4.8 Hz, 1H), 8.09 (d, J=8.4 Hz, 1H), 8.02 (d, J=8.0 Hz, 1H), 7.91 (br s, 1H), 7.72-7.68 (m, 5H), 7.54 (t, J=7.6 Hz, 1H), 6.87 (d, J=4.8 Hz, 1H), 3.88-3.82 (m, 6H), 3.28-3.20 (m, 4H), 2.95-2.89 (m, 1H), 2.50 (t, J=11.2 Hz, 1H), 2.27-2.24 (m, 1H), 2.22 (s, 3H), 1.91-1.83 (m, 2H), 1.77-1.74 (m 1H), 1.52-1.42 (m, 1H). LC-MS (ESI): Rt=3.270 min, m/z 522.2 [M+H].sup.+; purity: 98.70% @ 254 nm, 99.08% @ 214 nm.

##STR00129##

(R)-(1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0545] Except for using (R)-piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone instead of piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone, Formula 79 (40 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 78.

[0546] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 8.71 (d, J=4.8 Hz, 1H), 8.08 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.72 (t, J=7.2 Hz, 1H), 7.57 (t, J=7.2 Hz, 1H), 7.50 (d, J=8.8 Hz, 2H), 7.00 (d, J=4.8 Hz, 1H), 6.82 (d, J=8.8 Hz, 2H), 3.79-3.69 (m, 4H), 3.61-3.54 (m, 2H), 3.18-3.13 (m, 4H), 3.02 (s, 6H), 2.97-2.89 (m, 1H), 2.24 (t, J=11.2 Hz, 1H), 2.12-2.07 (m, 1H), 1.80-1.72 (m, 2H), 1.63-1.54 (m, 1H), 1.25-1.10 (m, 1H). LC-MS (ESI): Rt=3.475 min., m/z 508.2 [M+H].sup.+; purity: 97.01% @ 254 nm, 96.50% @ 214 nm.

[0547] chiral HPLC: Column: Chiralpak IA 5 um 4.6×250 mm; Mobile Phase: Hex EtOH:DEA=40:60:0.2 at 1 mL/min; Temp: 30° C.; Wavelength: 254 nm, Rt=19.497 min, 98.57% ee.

##STR00130##

(S)-(1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0548] Except for using (S)-piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone instead of piperidin-3-yl(4-(quinolin-4-yl)piperazin-1-yl)methanone, Formula 80 (42 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 78.

[0549] .sup.1HNMR (400 MHz, DMSO-d.sub.6): δ 8.71 (d, J=4.8 Hz, 1H), 8.08 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.72 (t, J=7.2 Hz, 1H), 7.57 (t, J=7.2 Hz, 1H), 7.50 (d, J=8.8 Hz, 2H), 7.00 (d, J=4.8 Hz, 1H), 6.82 (d, J=8.8 Hz, 2H), 3.79-3.69 (m, 4H), 3.61-3.55 (m, 2H), 3.18-3.13 (m, 4H), 3.02 (s, 6H), 2.96-2.90 (m, 1H), 2.24 (t, J=11.2 Hz, 1H), 2.12-2.07 (m, 1H), 1.80-1.72 (m, 2H), 1.65-1.59 (m, 1H), 1.25-1.15 (m, 1H). LC-MS (ESI): Rt=3.489 min., m/z 508.2 [M+H].sup.+; purity: 99.43% @ 254 nm, 99.17% @ 214 nm.

[0550] chiral HPLC: Column: Chiralpak IA 5 um 4.6×250 mm; Mobile Phase: Hex EtOH:DEA=40:60:0.2 at 1 mL/min; Temp: 30° C.; Wavelength: 254 nm, Rt=15.070 min, 99.52% ee.

##STR00131##

(1-(4-nitrophenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0551] Except for using 4-nitrobenzene-1-sulfonyl-chloride instead of benzenesulfonyl chloride, Formula 81 was obtained as a white solid in the same manner as in the preparation of the compound of Formula 74.

[0552] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.78 (d, J=4.8 Hz, 1H), 8.39 (d, J=8.8 Hz, 2H), 8.10 (d, J=8.4 Hz, 1H), 8.02 (d, J=8.4 Hz, 1H), 7.96 (d, J=9.2 Hz, 2H), 7.70 (t, J=6.8 Hz, 1H), 7.54 (t, J=7.2 Hz, 1H), 6.87 (d, J=4.8 Hz, 1H), 3.95-3.83 (m, 6H), 3.30-3.21 (m, 4H), 2.98-2.91 (m, 1H), 2.61 (t, J=11.6 Hz, 1H), 2.35-2.29 (m, 1H), 1.96-1.87 (m, 2H), 1.81-1.75 (m, 1H), 1.56-1.49 (m, 1H). LC-MS (ESI): Rt=3.734 min, m/z 510.2 [M+H].sup.+; purity: 97.44% @ 254 nm, 98.65% @ 214 nm.

##STR00132##

(1-(3-nitrophenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0553] Except for using 3-nitrobenzene-1-sulfonyl-chloride instead of benzenesulfonyl chloride, Formula 82 (56 mg) was obtained as a white solid in the same manner as for the preparation of the compound of Formula 74.

[0554] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.78 (d, J=5.2 Hz, 1H), 8.61 (s, 1H), 8.47 (d, J=8.4 Hz, 1H), 8.09 (d, J=8.0 Hz, 2H), 8.03 (d, J=8.4 Hz, 1H), 7.78 (t, J=8.0 Hz, 1H), 7.70 (t, J=8.0 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 6.87 (d, J=4.8 Hz, 1H), 3.95-3.79 (m, 6H), 3.33-3.21 (m, 4H), 2.98-2.92 (m, 1H), 2.61 (t, J=11.6 Hz, 1H), 2.40-2.33 (m, 1H), 1.96-1.88 (m, 2H), 1.82-1.76 (m, 1H), 1.58-1.48 (m, 1H). LC-MS (ESI): Rt=4.003 min, m/z 510.2 [M+H].sup.+; purity: 99.46% @ 254 nm, 98.15% @ 214 nm.

##STR00133##

(1-(4-(diethylamino)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0555] Except for using 4-(diedylamino)benzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 83 (35 mg) was obtained as a white solid in the same manner as in the preparation method of the compound of Formula 74.

[0556] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.78 (br s, 1H), 8.12-8.08 (m, 1H), 8.02 (d, J=8.0 Hz, 1H), 7.70 (t, J=7.2 Hz, 1H), 7.56-7.52 (m, 3H), 6.87 (d, J=4.8 Hz, 1H), 6.63 (d, J=9.2 Hz, 2H), 3.89-3.80 (m, 6H), 3.40 (q, J=7.2 Hz, 4H), 3.33-3.16 (m, 4H), 2.97-2.88 (m, 1H), 2.48 (t, J=11.6 Hz, 1H), 2.27-2.21 (m, 1H), 1.88-1.81 (m, 2H), 1.76-1.68 (m, 1H), 1.52-1.47 (m, 1H), 1.20 (t, J=6.8 Hz, 6H). LC-MS (ESI): Rt=3.827 min, m/z 536.3 [M+H].sup.+; purity: 94.48% @ 254 nm, 98.15% @ 214 nm.

##STR00134##

(4-(quinolin-4-yl)piperazin-1-yl)(1-(4-phenylbenzenesulfonyl) piperidin-3-yl)methanone

[0557] Except for using [1,1′-biphenyl]-4-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 84 (68 mg) was obtained as a white solid in the same manner as for the preparation of the compound of Formula 74.

[0558] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.78 (d, J=4.8 Hz, 1H), 8.10 (d, J=8.4 Hz, 1H), 8.02 (d, J=8.4 Hz, 1H), 7.84-7.82 (m, 2H), 7.75-7.68 (m, 3H), 7.62-7.60 (m, 2H), 7.56-7.41 (m, 4H), 6.87 (d, J=4.8 Hz, 1H), 3.95-3.82 (m, 6H), 3.33-3.21 (m, 4H), 2.99-2.91 (m, 1H), 2.58 (t, J=11.6 Hz, 1H), 2.35-2.29 (m, 1H), 1.93-1.85 (m, 2H), 1.82-1.75 (m, 1H), 1.56-1.47 (m, 1H). LC-MS (ESI): Rt=2.923 min, m/z 541.2 [M+H].sup.+; purity: 99.46% @ 254 nm, 99.22% @ 214 nm.

##STR00135##

(1-(4-bromophenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0559] Except for using 4-bromobenzene-1-sulfonyl-chloride instead of benzenesulfonyl chloride, Formula 85 (280 mg) was obtained as a white solid in the same manner as in the preparation method of the compound of Formula 74.

[0560] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.78 (d, J=4.8 Hz, 1H), 8.09 (d, J=8.8 Hz, 1H), 8.02 (d, J=8.0 Hz, 1H), 7.72-7.62 (m, 5H), 7.54 (t, J=7.6 Hz, 1H), 6.87 (d, J=5.2 Hz, 1H), 3.89-3.79 (m, 6H), 3.33-3.21 (m, 4H), 2.95-2.88 (m, 1H), 2.54 (t, J=11.2 Hz, 1H), 2.30-2.23 (m, 1H), 1.93-1.84 (m, 2H), 1.80-1.71 (m, 1H), 1.52-1.46 (m, 1H). LC-MS (ESI): Rt=8.996 min, m/z 543.1 [M+H].sup.+; purity: 97.53% @ 254 nm, 97.39% @214 nm.

##STR00136##

(1-(3-methoxyphenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0561] Except for using 3-methoxybenzene-1-sulfonyl chloride instead of benzenesulfonyl chloride, Formula 86 (40 mg) was obtained as a white solid in the same manner as for the preparation of the compound of Formula 74.

[0562] Rt=3.734 min, m/z 495.2 [M+H].sup.+; purity: 98.35% @ 254 nm, 98.12% @ 214 nm.

##STR00137##

N-(4-(3-(1-(7-methoxyquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl) phenyl)acetamide

[0563] Except for using (4-(7-methoxyquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone instead of (4-(2-methylquinolin-4-yl)piperazin-1-yl)(piperidin-3-yl)methanone, Formula 87 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 15.

[0564] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.68 (d, J=5.2 Hz, 1H), 7.90 (d, J=11.2 Hz, 1H), 7.70 (s, 5H), 7.41 (d, J=2.4 Hz, 1H), 7.17 (dd, J=11.2, 2.4 Hz, 1H), 6.76 (d, J=4.8 Hz, 1H), 3.95 (s, 3H), 3.87-3.82 (m, 6H), 3.25-3.18 (m, 4H), 2.90-2.87 (m, 1H), 2.49 (t, J=11.2 Hz, 1H), 2.27-2.24 (m, 1H), 2.22 (s, 3H), 1.90-1.82 (m, 2H), 1.73-1.70 (m, 1H), 1.49-1.45 (m, 1H). LC-MS (ESI): Rt=3.647 min, m/z 552.2 [M+H].sup.+; purity: 99.61% @ 254 nm, 98.55% @ 214 nm.

##STR00138##

(4-(7-methoxyquinolin-4-yl)piperazin-1-yl)(1-tosylpiperidin-3-yl)methanone

[0565] Except for using 4-methylbenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 88 (70 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 87.

[0566] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.68 (d, J=5.2 Hz, 1H), 7.90 (d, J=9.2 Hz, 1H), 7.64 (d, J=8.0 Hz, 2H), 7.40 (d, J=6.4 Hz, 1H), 7.32 (d, J=8.0 Hz, 2H), 7.17 (dd, J=9.2, 2.0 Hz, 1H), 6.75 (d, J=5.2 Hz, 1H), 3.95 (s, 3H), 3.87-3.82 (m, 6H), 3.26-3.17 (m, 4H), 2.91-2.89 (m, 1H), 2.50-2.45 (m, 1H), 2.43 (s, 3H), 2.22 (t, J=9.2 Hz, 1H), 1.89-1.81 (m, 2H), 1.74-1.71 (m, 1H), 1.49-1.45 (m, 1H). LC-MS(ESI): Rt=3.102 min, m/z 509.3 [M+H].sup.+; purity: 98.47% @ 254 nm, 98.37% @ 214 nm.

##STR00139##

(1-(4-fluorophenylsulfonyl)piperidin-3-yl)(4-(7-methoxyquinolin-4-yl)piperazin-1-yl)methanone

[0567] Except for using 4-fluorobenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 89 (65 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 87.

[0568] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.68 (d, J=4.8 Hz, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.80-7.76 (m, 2H), 7.41 (d, J=3.0 Hz, 1H), 7.24-7.16 (i, 3H), 6.75 (d, J=4.8 Hz, 1H), 3.95 (s, 3H), 3.88-3.80 (m, 6H), 3.25-3.17 (m, 4H), 2.92-2.89 (m, 1H), 2.52 (t, J=11.2 Hz, 1H), 2.25 (td, J=12.0, 2.8 Hz, 1H), 1.92-1.83 (m, 2H), 1.75-1.72 (m, 1H), 1.51-1.46 (m, 1H). LC-MS (ESI): Rt=3.923 min, m/z 513.2 [M+H].sup.+; purity: 99.40% @ 254 nm, 99.61% @ 214 nm.

##STR00140##

(1-(4-(dimethylamino)phenylsulfonyl)piperidin-3-yl)(4-(7-methoxyquinolin-4-yl)piperazin-1-yl)methanone

[0569] Except for using 4-(dimethylamino)benzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 90 (55 mg) was obtained as a white solid in the same manner as in the preparation method of the compound of Formula 87.

[0570] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.68 (d, J=4.8 Hz, 1H), 7.90 (d, J=9.2 Hz, 1H), 7.59 (d, J=8.8 Hz, 2H), 7.42 (d, J=3.0 Hz, 1H), 7.17 (dd, J=9.2, 2.8 Hz, 1H), 6.75 (d, J=5.2 Hz, 1H), 6.68 (d, J=9.2 Hz, 2H), 3.95 (s, 3H), 3.85-3.82 (m, 6H), 3.23-3.17 (m, 4H), 3.04 (s, 6H), 2.91-2.88 (m, 1H), 2.45 (t, J=11.2 Hz, 1H), 2.21-2.18 (m, 1H), 1.86-1.80 (m, 2H), 1.74-1.73 (m, 1H), 1.49-1.45 (m, 1H). LC-MS (ESI): Rt=4.023 min, m/z 538.3 [M+H].sup.+; purity: 99.35% @ 254 nm, 99.15% @ 214 nm.

##STR00141##

(1-(4-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(7-methoxyquinolin-4-yl)piperazin-1-yl)methanone

[0571] Except for using 4-hydroxybenzene-1-sulfonyl chloride instead of 4-acetamidobenzene-1-sulfonyl chloride, Formula 90 (78 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 87,

[0572] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 10.32 (br s, 1H), 8.62 (d, J=5.2 Hz, 1H), 7.97 (d, J=9.2 Hz, 1H), 7.57 (d, J=9.2 Hz, 2H), 7.34 (d, J=2.4 Hz, 1H), 7.20 (dd, J=9.2, 2.4 Hz, 1H), 6.97 (d, J=9.2 Hz, 2H), 6.87 (d, J=4.8 Hz, 1H), 3.90 (s, 3H), 3.77-3.70 (m, 4H), 3.61-3.56 (m, 2H), 3.17-3.09 (m, 4H), 2.95-2.90 (m, 1H), 2.27 (t, J=11.2 Hz, 1H), 2.12 (t, J=10.0 Hz, 1H), 1.80-1.74 (m, 2H), 1.65-1.57 (m, 1H), 1.25-1.17 (m, 1H). LC-MS (ESI): Rt=3.671 min, m/z 511.2 [M+H].sup.+; purity: 96.38% @ 254 nm, 96.15% @ 214 nm.

[0573] The target compound was synthesized according to Reaction Formula 1-2 for the following example compounds.

##STR00142##

##STR00143##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-(3-hydroxyphenylsulfonyl)piperidin-3-yl)methanone

[0574] A solution of (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((3-methoxyphenyl)sulfonyl)piperidin-3-yl)methanone (120 mg, 0.23 mmol) in DCM (15 mL) was cooled to −70° C. under a nitrogen atmosphere. BBr3 solution (17% in DCM, 1.0 g, 0.68 mmol) was added dropwise. The mixture was stirred at −70° C. for 30 min. After stirring at room temperature overnight, the mixture was poured into aqueous NaHCO.sub.3 solution (20 mL) and extracted with DCM (10 mL×3). The combined organic phases were washed with water (30 mL×2), brine (50 mL), dried over Na.sub.2SO.sub.4 and concentrated. The residue was purified by C18 chromatography using 30-80% CH.sub.3CN aqueous solution as a developing solvent to obtain the compound of Formula 92 (75 mg) as a white solid.

[0575] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 10.22 (s, 1H), 8.73 (d, J=5.2 Hz, 1H), 8.10 (d, J=9.2 Hz, 1H), 8.00 (d, J=2.4 Hz, 1H), 7.58 (dd, J=8.8, 2.4 Hz, 1H), 7.48-7.44 (m, 1H), 7.15 (d, J=7.6 Hz, 1H), 7.10-7.09 (m, 2H), 7.03 (d, J=5.2 Hz, 1H), 3.78-3.72 (m, 4H), 3.63-3.60 (m, 2H), 3.22-3.14 (m, 4H), 2.97-2.91 (m, 1H), 2.35 (t, J=11.2 Hz, 1H), 2.20 (td, J=10.0, 2.4 Hz, 1H), 1.81-1.72 (m, 2H), 1.62-1.59 (m, 1H), 1.25-1.21 (m, 1H). LC-MS (ESI): Rt=3.814 min, m/z 515.1 [M+H].sup.+; purity: 99.21% @ 254 nm, 98.97% @ 214 nm.

##STR00144##

(1-(3-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl) methanone

[0576] Except for using (1-(3-methoxyphenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone instead of (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((3-methoxyphenyl)sulfonyl)piperidin-3-yl)methanone, Formula 93 (35 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 92.

[0577] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 10.12 (s, 1H), 8.02 (d, J=8.4 Hz, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.66 (t, J=8.0 Hz, 1H), 7.51-7.44 (m, 2H), 7.15 (d, J=7.6 Hz, 1H), 7.10-7.08 (m, 2H), 6.92 (s, 1H), 3.78-3.60 (m, 6H), 3.19-3.13 (m, 4H), 2.96-2.90 (m, 1H), 2.58 (s, 3H), 2.36 (t, J=11.2 Hz, 1H), 2.20 (t, J=12.0 Hz, 1H), 1.82-1.72 (m, 2H), 1.62-1.59 (m, 1H), 1.29-1.20 (m, 1H). LC-MS (ESI): Rt=2.518 min, m/z 495.2 [M+H].sup.+; purity: 97.51% @ 254 nm, 98.12% @ 214 nm.

##STR00145##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-hydroxyphenylsulfonyl)piperidin-3-yl)methanone

[0578] Except for using (4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-methoxyphenylsulfonyl)piperidin-3-yl)methanone instead of (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((3-methoxyphenyl)sulfonyl)piperidin-3-yl)methanone, Formula 94 (30 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 92.

[0579] Rt=2.321 min, m/z 499.2 [M+H].sup.+; purity: 98.20% @ 254 nm, 98.22% @ 214 nm.

##STR00146##

(1-(3-hydroxyphenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0580] Except for using (1-(3-methoxyphenylphenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone instead of (4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-((3-methoxyphenyl)sulfonyl)piperidin-3-yl)methanone, Formula 95 (25 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 92.

[0581] Rt=2.241 min, m/z 481.2 [M+H].sup.+; purity: 98.11% @ 254 nm, 98.18% @ 214 nm.

[0582] The target compound was synthesized according to Reaction Formula 1-3 for the following example compounds.

##STR00147##

##STR00148##

(1-(4-aminophenylsulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone

[0583] According to Reaction Formula 1-3, (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-((4-nitrophenyl))piperidin-3-yl)methanone (0.48 g, 0.92 mmol, 1 eq) and Pd/C (30 mg, 0.28 mmol, 0.3 eq) is added. Then, the mixture was stirred under hydrogen for 5 hours. After that, it was filtered through Celite to remove Pd/C, and the filtrate was concentrated under reduced pressure. Then the residue was purified by C18 chromatography using 42 to 90% CH.sub.3CN aqueous solution as an eluent as a developing solvent to obtain the compound of Formula 96 (0.32 g) as a white solid.

[0584] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.02-7.95 (m, 2H), 7.66 (t, J=7.2 Hz, 1H), 7.54 (d, J=8.4 Hz, 2H), 7.47 (t, J=7.6 Hz, 1H), 6.75 (s, 1H), 6.69 (d, J=8.8 Hz, 2H), 4.14 (s, 2H), 3.96-3.73 (m, 6H), 3.30-3.11 (m, 4H), 2.95-2.87 (m, 1H), 2.70 (s, 1H), 2.48 (t, J=11.2 Hz, 1H), 2.26-2.18 (m, 1H), 1.89-1.81 (m, 2H), 1.76-1.73 (m, 1H), 1.54-1.47 (m, 1H). LC-MS (ESI): Rt=3.502 min, m/z 494.2 [M+H].sup.+; purity: 97.48% @ 254 nm, 96.45% @ 214 nm.

##STR00149##

(1-(4-aminophenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0585] Except for using (1-(4-nitrophenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone instead of (4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-((4-nitrophenyl))piperidin-3-yl)methanone, Formula 97 (100 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 94.

[0586] 1H NMR (400 MHz, DMSO-d.sub.6): δ 8.71 (d, J=4.8 Hz, 1H), 8.08 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.72 (t, J=7.6 Hz, 1H), 7.57 (t, J=7.6 Hz, 1H), 7.36 (d, J=8.4 Hz, 2H), 7.01 (d, J=5.2 Hz, 1H), 6.66 (d, J=8.4 Hz, 2H), 6.08 (s, 2H), 3.79-3.73 (m, 4H), 3.58-3.53 (m, 2H), 3.19-3.13 (m, 4H), 2.96-2.87 (m, 1H), 2.26 (t, J=11.2 Hz, 1H), 2.14-2.07 (m, 1H), 1.81-1.71 (m, 2H), 1.65-1.58 (m, 1H), 1.27-1.20 (m, 1H). LC-MS (ESI): Rt=3.923 min, m/z 480.1 [M+H].sup.+; purity: 97.44% @ 254 nm, 98.04% @ 214 nm.

[0587] The target compound was synthesized according to Reaction Formula 1-4 for the following example compounds.

##STR00150##

##STR00151##

4-((3-(1-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidin-1-yl)sulfonyl)benzoic acid

[0588] According to Reaction Formula 1-4, after dissolving methyl 4-((3-(4-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidin-1-yl)sulfonyl)benzoate (130 mg, 0.23 mmol) in MeOH (3 mL), LiOH.H.sub.2O (12 mg, 0.28 mmol) was added. After stirring at 70° C. for 1 h, the mixture was concentrated. The residue was diluted with water (5 mL) and 5% aqueous HCl solution was added to pH=4-5. The mixture was extracted with DCM (10 mL×3). The combined organic phases were washed with brine (5 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated to obtain a white solid. The obtained white solid was recrystallized using ethyl acetate (EtOAc) and n-hexane to obtain the compound of Formula 98 (95 mg) as a white solid.

[0589] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.73 (d, J=5.2 Hz, 1H), 8.18 (d, J=8.4 Hz, 2H), 8.11 (d, J=9.2 Hz, 1H), 8.01 (d, J=2.0 Hz, 1H), 7.87 (d, J=8.8 Hz, 2H), 7.59 (dd, J=8.4, 1.6 Hz, 1H), 7.04 (d, J=4.8 Hz, 1H), 3.79-3.65 (m, 6H), 3.22-3.14 (m, 4H), 2.97-2.92 (m, 1H), 2.38 (t, J=11.2 Hz, 1H), 2.26 (t, J=10.0 Hz, 1H), 1.82-1.73 (m, 2H), 1.66-1.60 (m, 1H), 1.29-1.23 (m, 1H). LC-MS (ESI): Rt=1.32 min, m/z 543.3 [M+H].sup.+; purity: 83% @ 254 nm, 92% @ 214 nm.

##STR00152##

4-(3-(1-(7-chloroquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)-N,N-dimethylbenzamide

[0590] After dissolving 4-((3-(4-(7-chloroquinolin-4-yl)piperazin-1-carbonyl)piperidin-1-yl)sulfonyl)benzoic acid (80 mg, 0.15 mmol), DIEA (95 mg, 0.74 mmol) and HATU (67 mg, 0.18 mmol) in DMF (5 mL), Dimethyl amine hydrochloride (24 mg, 0.29 mmol) was added. The mixture was stirred at room temperature for 5 hours. The mixture was diluted with water (20 ml-) and extracted with DCM (10 mL×3). The combined organic phases were washed with brine (5 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated. The residue was purified by C18 chromatography using 30-80% CH.sub.3CN aqueous solution to obtain the compound of Formula 99 (60 mg) as a white solid.

[0591] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.73 (d, J=5.2 Hz, 1H), 8.10 (d, J=9.2 Hz, 1H), 8.00 (d, J=2.4 Hz, 1H), 7.80 (d, J=8.4 Hz, 2H), 7.67 (d, J=7.6 Hz, 2H), 7.58 (dd, J=8.8, 2.0 Hz, 1H), 7.03 (d, J=5.2 Hz, 1H), 3.79-3.65 (m, 6H), 3.22-3.14 (m, 4H), 3.01 (s, 3H), 2.95-2.92 (m, 1H), 2.89 (s, 3H), 2.40 (t, J=11.2 Hz, 1H), 2.28-2.23 (m, 1H), 1.82-1.73 (m, 2H), 1.64-1.61 (m, 1H), 1.28-1.26 (m, 1H). LC-MS (ESI): Rt=2.623 min, m/z 570.2 [M+H].sup.+; purity: 99.23% @ 254 nm, 99.38% @ 214 nm.

##STR00153##

4-(3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)benzoic acid

[0592] Except for using methyl 4-((3-(4-(2-methylquinolin-4-yl)piperazin-1-carbonyl)piperidin-1-yl)sulfonyl)benzoate (230 mg, 0.43 mmol) instead of 4-((3-(4-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidin-1-yl)sulfonyl)benzoate, Formula 100 (200 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 98.

[0593] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.18 (d, J=8.4 Hz, 2H), 8.01 (d, J=8.0 Hz, 1H), 7.88-7.85 (m, 3H), 7.66 (t, J=7.2 Hz, 2H), 7.49 (t, J=7.2 Hz, 2H), 6.91 (s, 1H), 3.78-3.65 (m, 6H), 3.19-3.11 (m, 4H), 2.99-2.93 (m, 1H), 2.58 (s, 3H), 2.39 (t, J=11.6 Hz, 1H), 2.26 (t, J=12.0 Hz, 1H), 1.82-1.73 (m, 2H), 1.66-1.57 (m, 1H), 1.29-1.20 (m, 1H). LC-MS (ESI): Rt=1.26 min, m/z 523.3 [M+H].sup.+; purity: 100% @ 254 nm, 92% @214 nm.

##STR00154##

N,N-dimethyl-4-(3-(1-(2-methylquinolin-4-yl)piperazine-4-carbonyl)piperidin-1-ylsulfonyl)benzamide

[0594] Except for using 4-(3-(1-(2-methylquinolin-4-yl)piperazin-4-carbonyl)piperidin-1-ylsulfonyl)benzoic acid (200 mg, 0.38 mmol) instead of 4-((3-(4-(7-chloroquinolin-4-yl)piperazin-1-carbonyl)piperidin-1-yl)sulfonyl)benzoic acid, Formula 101 (60 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 99.

[0595] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.19 (d, J=8.0 Hz, 1H), 7.97-7.91 (m, 2H), 7.80 (d, J=8.0 Hz, 2H), 7.69-7.66 (m, 3H), 7.14 (s, 1H), 3.84-3.74 (m, 6H), 3.69-3.66 (m, 4H), 3.01 (s, 3H), 2.97-2.91 (m, 1H), 2.89 (s, 3H), 2.70 (s, 3H), 2.38 (t, J=11.2 Hz, 1H), 2.26 (td, J=12.6 Hz, 1H), 1.82-1.74 (m, 2H), 1.63-1.60 (m, 1H), 1.29-1.26 (m, 1H). LC-MS (ESI): Rt=3.606 min, m/z 550.2 [M+H].sup.+; purity: 95.46% @ 254 nm, 96.24% @ 214 nm.

[0596] The target compound was synthesized according to Reaction Formula 1-5 for the following example compounds.

##STR00155##

##STR00156##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-((4-(pyridin-4-yl)phenyl) sulfonyl)piperidin-3-yl)methanone

[0597] According to Scheme 1-5, under nitrogen atmosphere, after dissolving (1-((4-bromophenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone (180 mg, 0.32 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (79 mg, 0.38 mmol) in 1,4-dioxane (3 mL) solvent, 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (23 mg, 0.032 mmol) and sodium carbonate (68 mg, 0.64 mmol) were added at room temperature. After stirring at 100° C. for 20h, the mixture was concentrated. The residue was extracted with EtOAc (30 mL×3), then the organic layer was washed with water (30 mL×2) and brine (30 mL), dried over Na.sub.2SO.sub.4 and concentrated. The residue was first purified by silica gel chromatography using DCM:MeOH=40:1 to 20:1 as a developing solvent, final purification was performed by C18 chromatography using 20 to 90% CH.sub.3CN aqueous solution as a developing solvent to obtain the compound of Formula 102 (130 mg) as a white solid.

[0598] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.71 (d, J=4.2 Hz, 2H), 8.09 (d, J=8.0 Hz, 2H), 8.00 (d, J=8.0 Hz, 1H), 7.89-7.85 (m, 3H), 7.80 (d, J=5.6 Hz, 2H), 7.65 (t, J=7.2 Hz, 1H), 7.49 (t, J=7.6 Hz, 1H), 6.90 (s, 1H), 3.79-3.68 (m, 6H), 3.22-3.10 (m, 4H), 3.00-2.94 (m, 1H), 2.58 (s, 3H), 2.41 (t, J=11.6 Hz, 1H), 2.27 (t, J=12.8 Hz, 1H), 1.83-1.75 (m, 2H), 1.69-1.63 (m, 1H), 1.31-1.23 (m, 1H). LC-MS (ESI): Rt=3.722 min, m/z 556.2 [M+H].sup.+; purity: 97.22% @ 254 nm, 92.02% @ 214 nm.

##STR00157##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-((4-(pyrimidin-5-yl)phenyl) sulfonyl)piperidin-3-yl)methanone

[0599] Except for using 5-(4,4,5,5-tetramethyl-dioxaborolan-2-yl)pyrimidine instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, Formula 103 (120 mg) was obtained as a white solid by the same method as for the synthesis of Formula 102.

[0600] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 9.27-9.25 (m, 3H), 8.12 (d, J=8.0 Hz, 2H), 8.01 (d, J=8.4 Hz, 1H), 7.91-7.85 (m, 3H), 7.65 (t, J=8.0 Hz, 1H), 7.49 (t, J=7.6 Hz, 1H), 6.91 (s, 1H), 3.80-3.71 (m, 6H), 3.20-3.11 (m, 4H), 3.02-2.92 (m, 1H), 2.58 (s, 3H), 2.40 (t, J=12.0 Hz, 1H), 2.27 (t, J=9.6 Hz, 1H), 1.84-1.75 (m, 2H), 1.70-1.61 (m, 1H), 1.31-1.23 (m, 1H). LC-MS (ESI): Rt=3.575 min, m/z 557.2 [M+H].sup.+; purity: 99.68% @ 254 nm, 99.50% @ 214 nm.

##STR00158##

(1-((4-(2-methylpyrimidin-5-yl)phenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone

[0601] Except for using 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine instead of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, Formula 104 (50 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 102.

[0602] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 9.12 (s, 2H), 8.08 (d, J=8.4 Hz, 2H), 8.01 (d, J=8.4 Hz, 1H), 7.89-7.85 (m, 3H), 7.65 (t, J=8.0 Hz, 1H), 7.49 (t, J=7.2 Hz, 1H), 6.90 (s, 1H), 3.79-3.67 (m, 6H), 3.21-3.11 (m, 4H), 3.00-2.94 (m, 1H), 2.69 (s, 3H), 2.58 (s, 3H), 2.39 (t, J=11.2 Hz, 1H), 2.26 (t, J=11.6 Hz, 1H), 1.83-1.74 (m, 2H), 1.68-1.63 (m, 1H), 1.29-1.23 (m, 1H). LC-MS (ESI): Rt=3.734 min, m/z 571.3 [M+H].sup.+; purity: 97.75% @ 254 nm, 95.87% @ 214 nm.

##STR00159##

(4-(2-methylquinolin-4-yl)piperazin-1-yl)(1-((4-(pyridin-3-yl)phenyl)sulfonyl)piperidin-3-yl)methanone

[0603] Except for using 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, Formula 105 (40 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 102.

[0604] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 9.00 (d, J=2.0 Hz, 1H), 8.65 (dd, J=4.8, 1.6 Hz, 1H), 8.20 (d, J=8.4 Hz, 1H), 8.05-8.00 (m, 3H), 7.88-7.86 (m, 3H), 7.65 (t, J=7.2 Hz, 1H), 7.56-7.54 (m, 1H), 7.51 (t, J=7.6 Hz, 1H), 6.90 (s, 1H), 3.80-3.68 (m, 6H), 3.18-3.10 (m, 4H), 3.01-2.95 (m, 1H), 2.58 (s, 3H), 2.40 (t, J=11.6 Hz, 1H), 2.27 (t, J=9.6 Hz, 1H), 1.83-1.75 (m, 2H), 1.69-1.63 (m, 1H), 1.31-1.23 (m, 1H). LC-MS (ESI): Rt=3.355 min, m/z 556.2 [M+H].sup.+; purity: 99.31% @ 254 nm, 98.73% @ 214 nm.

##STR00160##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-(pyridin-4-yl)phenylsulfonyl) piperidin-3-yl)methanone

[0605] Except for using (1-(4-bromophenylsulfonyl)piperidin-3-yl)(4-7-fluoroquinolin-4-yl)piperazin-1-yl)methanone (200 mg, 0.36 mmol) instead of (1-((4-Bromophenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, Formula 106 (40 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 102.

[0606] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.78-8.74 (m, 3H), 8.05-8.01 (m, 1H), 7.90-7.88 (m, 2H), 7.79-7.77 (m, 2H), 7.74-7.71 (m, 1H), 7.52 (d, J=6.0 Hz, 2H), 7.34-7.29 (m, 1H), 6.85 (d, J=5.2 Hz, 1H), 3.95-3.80 (m, 6H), 3.32-3.19 (m, 4H), 3.00-2.91 (m, 1H), 2.56 (t, J=11.2 Hz, 1H), 2.35-2.26 (m, 1H), 1.94-1.86 (m, 2H), 1.81-1.72 (m, 1H), 1.53-1.49 (m, 1H). LC-MS (ESI): Rt=3.592 min, m/z 560.3 [M+H].sup.+; purity: 96.47% @254 nm, 92.98% @ 214 nm.

##STR00161##

(R)-(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-(pyridin-4-yl)phenylsulfonyl) piperidin-3-yl)methanone

[0607] Except for using (R)-1-(4-bromophenylsulfonyl)piperidin-3-yl)(4-7-fluoroquinolin-4-yl)piperazin-1-yl)methanone instead of (1-(4-Bromophenylsulfonyl)piperidin-3-yl)(4-7-fluoroquinolin-4-yl)piperazin-1-yl)methanone, Formula 107 (50 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 106.

[0608] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.78-8.74 (m, 3H), 8.05-8.01 (m, 1H), 7.90-7.88 (m, 2H), 7.79-7.77 (m, 2H), 7.74-7.71 (m, 1H), 7.53-7.52 (m, 2H), 7.34-7.29 (m, 1H), 6.85 (d, J=5.2 Hz, 1H), 3.95-3.82 (m, 6H), 3.32-3.20 (m, 4H), 2.99-2.92 (m, 1H), 2.58 (t, J=10.8 Hz, 1H), 2.34-2.28 (m, 1H), 1.93-1.86 (m, 2H), 1.79-1.75 (m, 1H), 1.55-1.49 (m, 1H). LC-MS (ESI): Rt=3.513 min, m/z 560.2 [M+H].sup.+; purity: 98.02% @ 254 nm, 95.61% @ 214 nm.

[0609] chiral HPLC: Column: Chiralpak IB 5 um 4.6×250 mm; Mobile Phase: Hex EtOH=40:60 at 1 mL/min; Temp: 30° C.; Wavelength: 254 nm, Rt=12.689 min, 99.23% ee.

##STR00162##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-(pyridin-3-yl)phenylsulfonyl)piperidin-3-yl)methanone

[0610] Except for using 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine instead of (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, Formula 108 (30 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 106.

[0611] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.89-8.88 (m, 1H), 8.77 (d, J=4.8 Hz, 1H), 8.69-8.68 (m, 1H), 8.05-8.01 (m, 1H), 7.93-7.87 (m, 3H), 7.75-7.71 (m, 3H), 7.46-7.42 (m, 1H), 7.34-7.29 (m, 1H), 6.85 (d, J=5.2 Hz, 1H), 3.95-3.80 (m, 6H), 3.33-3.21 (m, 4H), 2.98-2.93 (m, 1H), 2.58 (t, J=11.2 Hz, 1H), 2.35-2.29 (m, 1H), 1.94-1.86 (m, 2H), 1.78-1.75 (m, 1H), 1.56-1.49 (m, 1H). LC-MS (ESI): Rt=3.513 min, m/z 560.2 [M+H].sup.+; purity: 98.31% @ 254 nm, 96.48% @ 214 nm.

##STR00163##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-(pyridin-4-yl)phenylsulfonyl)piperidin-3-yl)methanone

[0612] Except for using (1-(3-bromophenylsulfonyl)piperidin-3-yl)(4-7-fluoroquinolin-4-yl)piperazin-1-yl)methanone instead of (1-(4-Bromophenylsulfonyl)piperidin-3-yl)(4-7-fluoroquinolin-4-yl)piperazin-1-yl)methanone, Formula 109 (25 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 106.

[0613] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.77-8.72 (m, 3H), 8.04-8.01 (m, 2H), 7.88-7.83 (m, 2H), 7.75-7.67 (m, 2H), 7.54-7.53 (m, 2H), 7.34-7.30 (m, 1H), 6.84 (d, J=5.2 Hz, 1H), 3.95-3.83 (m, 6H), 3.30-3.21 (m, 4H), 2.99-2.91 (m, 1H), 2.59 (t, J=10.8 Hz, 1H), 2.36-2.29 (m, 1H), 1.94-1.85 (m, 2H), 1.79-1.74 (m, 1H), 1.52-1.48 (m, 1H). LC-MS (ESI): Rt=3.512 min, m/z 560.3 [M+H].sup.+; purity: 95.67% @ 254 nm, 96.72% @ 214 nm.

##STR00164##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-(pyridin-3-yl)phenylsulfonyl)piperidin-3-yl)methanone

[0614] Except for using 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine instead of (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, Formula 110 (20 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 109,

[0615] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.88-8.87 (m, 1H), 8.77 (d, J=4.8 Hz, 1H), 8.68-8.66 (m, 1H), 8.04-8.00 (m, 1H), 7.97-7.94 (m, 1H), 7.93-7.90 (m, 1H), 7.84-7.79 (m, 2H), 7.73-7.65 (m, 2H), 7.44-7.41 (m, 1H), 7.34-7.29 (m, 1H), 6.84 (d, J=5.2 Hz, 1H), 3.94-3.83 (m, 6H), 3.29-3.19 (m, 4H), 2.98-2.91 (m, 1H), 2.59 (t, J=11.2 Hz, 1H), 2.37-2.31 (m, 1H), 1.93-1.85 (m, 2H), 1.81-1.74 (m, 1H), 1.54-1.50 (m, 1H). LC-MS (ESI): Rt=3.520 min, m/z 560.2 [M+H].sup.+; purity: 98.73% @ 254 nm, 98.60% @ 214 nm.

##STR00165##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(4-(pyrimidin-5-yl)phenylsulfonyl)piperidin-3-yl)methanone

[0616] Except for using 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine instead of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, Formula 111 (77 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 105.

[0617] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 9.30 (s, 1H), 9.00 (s, 2H), 8.77 (d, J=4.8 Hz, 1H), 8.03 (dd, J=9.6, 6.0 Hz, 1H), 7.94-7.92 (d, J=8.4 Hz, 2H), 7.76-7.70 (m, 3H), 7.34-7.29 (m, 1H), 6.84 (d, J=5.2 Hz, 1H), 3.95-3.84 (m, 6H), 3.29-3.20 (m, 4H), 2.99-2.93 (m, 1H), 2.59 (t, J=11.2 Hz, 1H), 2.36-2.28 (m, 1H), 1.94-1.87 (m, 2H), 1.82-1.76 (m, 1H), 1.56-1.45 (m, 1H). LC-MS (ESI): Rt=3.790 min, m/z 561.2 [M+H].sup.+; purity: 96.04% @ 254 nm, 97.05% @ 214 nm.

##STR00166##

(4-(7-fluoroquinolin-4-yl)piperazin-1-yl)(1-(3-(pyrimidin-5-yl)phenylsulfonyl)piperidin-3-yl)methanone

[0618] Except for using (1-(3-bromophenylsulfonyl)piperidin-3-yl)(4-7-fluoroquinolin-4-yl)piperazin-1-yl)methanone instead of (1-(4-Bromophenylsulfonyl)piperidin-3-yl)(4-7-fluoroquinolin-4-yl)piperazin-1-yl)methanone, Formula 112 (50 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 109.

[0619] LC-MS (ESI): Rt=3.783 min, m/z 561.2 [M+H].sup.+; purity: 95.88% @ 254 nm, 96.03% @ 214 nm.

##STR00167##

(1-(4-(pyridin-4-yl)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0620] Except for using (1-(4-bromophenylphenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone (250 mg, 0.46 mmol) instead of (1-((4-Bromophenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, Formula 113 (40 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 102.

[0621] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.78-8.73 (m, 3H), 8.10 (d, J=8.4 Hz, 1H), 8.02 (d, J=8.4 Hz, 1H), 7.90-7.88 (m, 2H), 7.79-7.77 (m, 2H), 7.72-7.68 (m, 1H), 7.56-7.51 (m, 3H), 6.87 (d, J=4.8 Hz, 1H), 3.95-3.81 (m, 6H), 3.35-3.22 (m, 4H), 3.00-2.92 (m, 1H), 2.58 (t, J=11.2 Hz, 1H), 2.34-2.27 (m, 1H), 1.95-1.86 (m, 2H), 1.82-1.72 (m, 1H), 1.53-1.46 (m, 1H). LC-MS (ESI): Rt=3.900 min, m/z 542.2 [M+H].sup.+; purity: 98.27% @254 nm, 97.25% @ 214 nm.

##STR00168##

(1-(4-(pyridin-3-yl)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0622] Except for using 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine instead of (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, Formula 114 (30 mg) was obtained as a white solid in the same manner as in the preparation of the compound of Formula 113.

[0623] LC-MS (ESI): Rt=3.881 min, m/z 542.2 [M+H].sup.+; purity: 98.11% @ 254 nm, 98.05% @ 214 nm.

##STR00169##

(1-(4-(2-methylpyrimidin-5-yl)phenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone

[0624] Except for using (1-(4-bromophenylphenylsulfonyl)piperidin-3-yl)(4-(quinolin-4-yl)piperazin-1-yl)methanone instead of (1-((4-Bromophenyl)sulfonyl)piperidin-3-yl)(4-(2-methylquinolin-4-yl)piperazin-1-yl)methanone, Formula 115 (32 mg) was obtained as a white solid in the same manner as for the preparation of compound of Formula 103.

[0625] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.89 (s, 2H), 8.78 (d, J=4.8 Hz, 1H), 8.10 (d, J=8.4 Hz, 1H), 8.02 (d, J=8.0 Hz, 1H), 7.91-7.89 (m, 2H), 7.74-7.68 (m, 3H), 7.54 (t, J=7.2 Hz, 1H), 6.87 (d, J=4.8 Hz, 1H), 3.95-3.80 (m, 6H), 3.33-3.21 (m, 4H), 3.01-2.94 (m, 1H), 2.83 (s, 3H), 2.57 (t, J=11.6 Hz, 1H), 2.31-2.28 (m, 1H), 1.94-1.86 (m, 2H), 1.82-1.75 (m, 1H), 1.56-1.45 (m, 1H). LC-MS (ESI): Rt=5.967 min, m/z 557.3 [M+H].sup.+; purity: 93.22% @ 254 nm, 94.98% @ 214 nm.

##STR00170##

##STR00171##

N-(4-(3-(4-(7-chloroquinolin-4-yl)piperazine-1-carbonyl)piperidin-1-ylsulfonyl)phenyl)acetamide

[0626] According to Reaction Formula 2, 1-((4-acetamidophenyl)sulfonyl)piperidine-3-carboxylic acid (2.0 g, 6.13 mmol) and DIPEA (24.51 mmol) were added to 50 ml of dichloromethane, and stirred at 0° C. for 15 minutes. Thereafter, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) (2.38 g, 15.32 mmol) and hydroxybenzotriazole (HOBT) (2.07 g, 15.32 mmol) were added at 0° C. After 30 minutes, 7-chloro-4-(piperazin-1-yl)quinoline (1.52 g, 6.13 mmol) was added and stirred at room temperature for 12 hours. Into 100 ml of water, dichloromethane (60 ml×3) was added to separate the organic material layer, then dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure. Purification was performed by column chromatography using methanol (5-10%) and dichloromethane as developing solvents to obtain the target compound, Formula 116 (1.9 g) as a white solid.

[0627] .sup.1H NMR (400 MHz, CDCl.sub.3): δ 8.74 (d, J=4.8 Hz, 1H), 8.10 (d, J=2.0 Hz, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.70-7.68 (m, 5H), 7.43 (dd, J=9.2, 2.0 Hz, 1H), 6.86 (d, J=4.2 Hz, 1H), 3.87-3.82 (m, 6H), 3.31-3.20 (m, 4H), 2.93-2.87 (m, 1H), 2.50 (t, J=11.6 Hz, 1H), 2.28-2.25 (m, 1H), 2.22 (s, 3H), 1.90-1.82 (m, 2H), 1.78-1.72 (m, 1H), 1.52-1.42 (m, 1H). LC-MS (ESI): Rt=3.967 min, m/z 556.2 [M+H].sup.+; purity: 98.64% @ 254 nm, 98.20% @ 214 nm.

##STR00172##

(4-(7-chloroquinolin-4-yl)piperazin-1-yl)(1-(4-nitrophenylsulfonyl)piperidin-3-yl)methanone

[0628] Except for using 1-((4-nitrophenyl)sulfonyl)piperidine-3-carboxylic acid instead of 1-((4-acetamidophenyl)sulfonyl)piperidine-3-carboxylic acid and, the compound of Formula 117 (120 mg) was obtained as a pale yellow solid in the same manner as in the preparation of the compound of Formula 116.

[0629] .sup.1H NMR (400 MHz, DMSO_d.sub.6): δ 8.73 (d, J=4.2 Hz, 1H), 8.46 (d, J=8.0 Hz, 2H), 8.10 (d, J=8.8 Hz, 1H), 8.03 (d, J=8.8 Hz, 2H), 8.02-8.00 (m, 1H), 7.58 (dd, J=9.2, 2.4 Hz, 1H), 7.03 (d, J=4.8 Hz, 1H), 3.79-3.68 (m, 6H), 3.25-3.11 (m, 4H), 3.00-2.92 (m, 1H), 2.45-2.42 (m, 1H), 2.33 (t, J=11.6 Hz, 1H), 1.83-1.74 (m, 2H), 1.68-1.57 (m, 1H), 1.29-1.20 (m, 1H). LC-MS (ESI): Rt=3.760 min, m/z 544.2 [M+H].sup.+; purity: 97.70% @ 254 nm, 96.90% @ 214 nm.

Example 3: Selection of Compounds Exhibiting CYP4A Inhibitory Activity

[0630] The present inventors selected CYP4A inhibitors through screening of commercially available compounds and novel synthetic compounds, based on the content of the prior invention that compounds exhibiting CYP4A inhibitory activity can exhibit preventive or therapeutic effects on diabetes and fatty liver. A commercially available reagent was used for the reagent used in the experiment, and it was manufactured and used if necessary. The device used for activity measurement was EnVision of PerkinElmer or SpectraMax of MOLECULAR DEVICES.

[0631] First, CYP4A bactosome and synthetic compound (5 μM) were mixed in assay buffer (100 mM KPO4, 0.1% BSA, 1 mM DTT) in a 384-well plate (white opaque ploystyrene nontreated flat-bottom well), and then reacted at room temperature for 15 minutes. After adding 5 mM Luciferin-ME and NADPH Regeneration system (1 OX sol.A, 20× sol.B in assay buffer, Cat. Number: V865B, Promega), leave it at room temperature for 30 minutes to allow the CYP4A reaction to occur sufficiently, by adding the Luciferin Detection reagent, the CYpnA reaction was finished, luminescence reaction was induced, and the reaction was carried out at room temperature for 15 minutes. The degree of inhibition of CYNA activity was measured by comparing the luminescence values from each well with a microplate reader.

[0632] The results are shown in Table 1 below.

TABLE-US-00001 TABLE 1 Inhibition of CYP4A of Quinoline Compounds CYP4A enzyme assay (compound concentration 5 μM) % Inhibition Compound no. 25% or less 25%-50% 50%-75% 75% or more Formula 1 ◯ Formula 2 ◯ Formula 3 ◯ Formula 4 ◯ Formula 5 ◯ Formula 6 ◯ Formula 7 ◯ Formula 8 ◯ Formula 9 ◯ Formula 10 ◯ Formula 11 ◯ Formula 12 ◯ Formula 13 ◯ Formula 14 ◯ Formula 15 ◯ Formula 16 ◯ Formula 17 ◯ Formula 18 ◯ Formula 19 ◯ Formula 20 ◯ Formula 21 ◯ Formula 22 ◯ Formula 23 ◯ Formula 24 ◯ Formula 25 ◯ Formula 26 ◯ Formula 27 ◯ Formula 28 ◯ Formula 29 ◯ Formula 30 ◯ Formula 31 ◯ Formula 32 ◯ Formula 33 ◯ Formula 34 ◯ Formula 35 ◯ Formula 36 ◯ Formula 37 ◯ Formula 38 ◯ Formula 39 ◯ Formula 40 ◯ Formula 41 ◯ Formula 42 ◯ Formula 43 ◯ Formula 44 ◯ Formula 45 ◯ Formula 46 ◯ Formula 47 ◯ Formula 48 ◯ Formula 49 ◯ Formula 50 ◯ Formula 51 ◯ Formula 52 ◯ Formula 53 ◯ Formula 54 ◯ Formula 55 ◯ Formula 56 ◯ Formula 57 0 Formula 58 ◯ Formula 59 ◯ Formula 60 ◯ Formula 61 ◯ Formula 62 ◯ Formula 63 ◯ Formula 64 ◯ Formula 65 ◯ Formula 66 ◯ Formula 67 ◯ Formula 68 ◯ Formula 69 ◯ Formula 70 ◯ Formula 71 ◯ Formula 72 ◯ Formula 73 ◯ Formula 74 ◯ Formula 75 ◯ Formula 76 ◯ Formula 77 ◯ Formula 78 ◯ Formula 79 ◯ Formula 80 ◯ Formula 81 ◯ Formula 82 ◯ Formula 83 ◯ Formula 84 ◯ Formula 85 ◯ Formula 86 ◯ Formula 87 0 Formula 88 0 Formula 89 ◯ Formula 90 ◯ Formula 91 ◯ Formula 92 ◯ Formula 93 ◯ Formula 94 ◯ Formula 95 ◯ Formula 96 ◯ Formula 97 0 Formula 98 ◯ Formula 99 ◯ Formula 100 ◯ Formula 101 ◯ Formula 102 0 Formula 103 ◯ Formula 104 0 Formula 105 0 Formula 106 0 Formula 107 ◯ Formula 108 ◯ Formula 109 ◯ Formula 110 ◯ Formula 111 ◯ Formula 112 ◯ Formula 113 ◯ Formula 114 ◯ Formula 115 ◯ Formula 116 ◯ Formula 117 ◯ HET-0016 ◯

[0633] As a result, as shown in Table 1, it was confirmed that most of the compounds having the structure of Formula (I) provided in the present invention had the inhibitory ability of CYP4A.

Example 4: Confirmation of the Effect of the Compound of the Present Invention on the Induction of ER Stress in Hepatocytes

[0634] 4-1. Glucose Absorption Promoting Effect

[0635] HepG2 cells, a human liver cell line, were cultured in a high-glucose DMEM (Dulbecco's modified Eagle's medium) medium in the presence of 10% fetal bovine serum (FBS), and then glucose uptake experiments were performed as follows.

[0636] First, put HepG2 cells in a 96-well plate (black, clear bottom culture plate) at 2×10.sup.4 cells/well and incubate in an incubator for 24 hours. Thapsigargin (1 μM, hereinafter Thap), which induces endoplasmic reticulum stress, and compounds exhibiting excellent CYP4A inhibitory activity among the compounds synthesized in the above Examples were selected, each compound was added (5 uM), and the reaction was put in an incubator for 24 hours.

[0637] After that, the experiment is performed using a glucose uptake assay kit (Cat. Number: 600470, Cayman). Dilute 2-NBDG (2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose) in a glucose-free culture medium and incubate at 37° C. 1 minute. After washing the wells twice using a phosphate buffered saline (PBS) buffer, fluorescence (Excitation: 485 nm, Emission: 535 nm) was measured with a microplate reader.

[0638] As a result, as can be seen in FIG. 1, in the control group treated only with thapsigargin without treatment with the test substance, glucose uptake was decreased compared to the negative control group, but when thapsigargin and the compound of the present invention were treated, glucose absorption was improved to the level of the negative control group, and this effect was confirmed to be equal to or greater than that of HET0016.

[0639] 4-2. Fat Accumulation Improvement Effect

[0640] After culturing HepG2 cells, a human liver cell line, in a high glucose DMEM (Dulbecco's modified Eagle's medium, glucose 25 mM) medium containing 10% fetal bovine serum (FBS), an experiment was conducted to measure fat accumulation in the following way.

[0641] First, HepG2 cells were grown to 5×10.sup.3 cells/well in a 96-well plate (black, clear bottom culture plate) by the above method, and compounds showing excellent CYP4A inhibitory activity among the compounds synthesized in the above Examples were selected and each compound (5 μM) was added and incubated for 6 hours. Here, after putting thapsigargin inducing endoplasmic reticulum stress, the reaction was put into an incubator at 37° C. for 24 hours. After that, 4% paraformaldehyde was added and reacted at room temperature for 15 minutes to fix, and then Nile-Red solution was added, light was blocked, and reaction was performed at 37° C. for 10 minutes. After the reaction time, fluorescence was measured with a microplate reader (Excitation: 530 nm, Emission: 635 nm).

[0642] As a result, as can be seen in FIG. 2, it was confirmed that a large amount of fat was accumulated in the control cells treated with thapsigargin without the test substance treatment as compared to the negative control group. In contrast, in the test group treated with the effective compound of the present invention, it was found that the accumulation of fat in the liver cells was reduced to HET0016 or more.

[0643] 4-3. Active Oxygen Scavenging Ability

[0644] After culturing HepG2 cells, a human liver cell line, in high glucose concentration DMEM (Dulbecco's modified Eagle's medium, glucose 25 mM) medium with of 10% FBS (fetal bovine serum), an experiment was conducted to measure the ability to remove active oxygen in the following way.

[0645] First, HepG2 cells were grown to 1×10.sup.4 cells/well in a 96-well plate (black, clear bottom culture plate) by the above method, and compounds showing excellent CYP4A inhibitory activity among the compounds synthesized in the above Examples were selected and each compound (5 μM) was added and incubated for 6 hours. Here, thapsigargin inducing endoplasmic reticulum stress was added, and then put into an incubator at 37° C. for 24 hours to react, and then 5 μM H.sub.2DCFDA (cell-permeant 2′,7′-dichlorodihydrofluorescein diacetate) was added to react for 30 minutes in an incubator at 37° C. Thereafter, after washing with PBS, it was placed in an incubator at 37° C. for 30 minutes and waited for luminescence to occur. Thereafter, fluorescence was measured with a microplate reader (Excitation: 488 nm, Emission: 508 nm).

[0646] As a result, as can be seen in FIG. 3, it was confirmed that the amount of ROS was rapidly increased in the control group treated only with thapsigargin compared to the negative control group. In contrast, the group treated with the effective compound of the present invention confirmed that the amount of ROS was significantly lowered, and it was confirmed that the occurrence of ROS was reduced to a level similar to that of the negative control group.

[0647] Through the results of FIGS. 1, 2 and 3, it was confirmed that the compound of the present invention has the effect of treating/improving diabetes, such as lowering blood sugar by promoting glucose absorption in hepatocytes in the presence of endoplasmic reticulum stress, and it can have an effect on fatty liver disease, such as improving lipid accumulation or oxidative stress in liver cells.

INDUSTRIAL APPLICABILITY

[0648] The novel quinoline compound disclosed in the present invention has a remarkable CYP4A inhibitory effect, and it exhibits activities such as promoting glucose absorption into hepatocytes, inhibiting fat accumulation in hepatocytes, inhibiting reactive oxygen species caused by ER stress and treating steatohepatitis, and it can be very usefully used in the development of therapeutics for metabolic diseases such as diabetes, steatohepatitis, and obesity, so it has excellent industrial applicability.