Granted Patent B2

US 12,552,767 · App. 18/254,190 · Granted Feb 17, 2026

Inventors: Stephane L. Bogen (Somerset, NJ); Ping Chen (Edison, NJ); Dane James Clausen (Rahway, NJ); Xianhai Huang (Warren, NJ); Michael T. Rudd (Collegeville, PA); Shawn P. Walsh (Bridgewater, NJ); Lan Wei (Berkeley Heights, NJ); Dexi Yang (Livingston, NJ)

Assignee: Merck Sharp & Dohme LLC

C07D401/04C07D401/14C07D403/04C07D405/14C07D413/14C07D417/04

Abstract

Claims (218)

1 . A compound of the formula I:

wherein:

n is 1 or 2;

A is a furanyl, imidazolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, phenyl, pyrazinyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrrolopyridinyl, furopyridinyl, isoxazolopyridinyl, tetrazolyl, 1,3,4-thiadiazol, thiazolyl, thiophenyl or triazolyl ring, or an N-oxide thereof,

X is —O— or —NH—, or X may be a direct bond to R 1 ;

Y is N or CH;

R 1 is selected from:

(1) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one to six substituents independently selected from R 4 , and

(2) —C 3-6 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one to six substituents independently selected from R 4 ;

(3) —CH 2 —C 3-6 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one to six substituents independently selected from R 4 ;

(4) —C 2-6 alkenyl, and

(5) —C 2-6 alkynyl;

R 1a , R 1b and R 1c as present are independently selected from:

(1) hydrogen,

(2) halogen,

(3) hydroxyl,

(4) C 1-6 alkyl, which is unsubstituted or substituted with substituents selected from: hydroxy, fluoro and phenyl,

(5) —O—C 1-6 alkyl, which is unsubstituted or substituted with substituents selected from: fluoro and phenyl,

(6) C 3-6 cycloalkyl,

(7) C 2-6 alkynyl,

(8) —NH 2 ,

(9) —NH(C 1-6 alkyl),

(10) —N(C 1-6 alkyl) 2 ,

(11) —(CO)—O—C 1-6 alkyl,

(12) keto,

(13) tetrahydropyranyl,

(14) -phenyl,

(15) -pyridyl, and

(16) —CN;

R 2 is selected from:

(1) hydrogen,

(2) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one to six substituents independently selected from R 4 ,

(3) —C 3-6 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one to six substituents independently selected from R 4 ,

(4) -phenyl, where the phenyl is unsubstituted or substituted with one to three substituents independently selected from R 4 , and

(5) -heteroaryl, where the heteroaryl is selected from: pyridyl, pyrimidinyl, and pyrazinyl, and the heteroaryl is unsubstituted or substituted with one to three substituents independently selected from R 4 ;

R 2a and R 2b are independently selected from:

(1) hydrogen,

(2) hydroxyl,

(3) halogen, and

(4) —C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one to six substituents independently selected from halogen;

R 4 is selected from:

(1) hydroxyl,

(2) halogen,

(3) C 1-6 alkyl, which is unsubstituted or substituted with one to six fluoro,

(4) —C 3-6 cycloalkyl,

(5) —O—C 1-6 alkyl,

(6) —O(C═O)—C 1-6 alkyl,

(7) —(C═O)—C 1-6 alkyl,

(8) —NH 2 ,

(9) —NH—C 1-6 alkyl,

(10) —NO 2 ,

(11) oxetanyl,

(12) phenyl, which is unsubstituted or substituted with one to three halo,

(13) pyridyl,

(14) oxazolyl, which is unsubstituted or substituted with —C 1-6 alkyl,

(15) oxomorpholinyl, which is unsubstituted or substituted with —C 1-6 alkyl,

(16) —CO 2 H, and

(17) —CN;

R 5 and R 6 are independently selected from:

(1) hydrogen,

(2) C 1-6 alkyl, where the alkyl is unsubstituted or substituted with one to six substituents independently selected from R 4 , and

(3) —C 3-6 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one to six substituents independently selected from R 4 ,

or R 5 and R 6 are joined together with the carbon atoms to which they are attached to form a —C 3-6 cycloalkyl ring, where the cycloalkyl is unsubstituted or substituted with one to six substituents independently selected from R 4 ;

or a pharmaceutically acceptable salt thereof.

2 . The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein n is 2.

3 . The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein A is a pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, thiazol-4-yl, or 1,2,4-triazol-5-yl ring.

4 . The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein X is —O—.

5 . The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein X is a direct bond to R 1 .

6 . The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 1 is selected from:

(1) methyl,

(2) ethyl,

(3) —CH 2 OH,

(4) —CH 2 CF 3 ,

(5) —CH 2 CHF 2 ,

(6) —CH(CH 3 ) 2 ,

(7) —CH 2 CH 2 CH 2 F,

(8) cyclopropyl,

(8) cyclopropyl-CH 3 ,

(9) —CH 2 -cyclopropyl,

(10) —CH 2 -cyclobutyl, and

(11) —CH 2 O(C═O)CH 3 .

7 . The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 2 is selected from:

(1) hydrogen,

(2) —CH 2 (CH 3 ) 2 ,

(3) —CF 3 ,

(4) —CH 2 CHF 2 ,

(5) —CH 2 CF 3 , and

(6) phenyl, which is unsubstituted or substituted with —CF 3 or —CH 2 CF 3 .

8 . The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 2a is hydrogen and R 2b is hydrogen.

9 . The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 5 is hydrogen and R 6 is hydrogen.

10 . A compound which is selected from:

(CIS)-N-ethyl-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-5-yl)piperidine-1-carboxamide;

methyl (CIS)-3-(2-hydroxy-5-methylthiazol-4-yl)-2-((((CIS)-4-phenyl-cyclohexyl)oxy)-methyl)piperidine-1-carboxylate;

(CIS)-N-ethyl-2-(((4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-5-yl)piperidine-1-carboxamide;

(2R,3S)—N-ethyl-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-5-yl)piperidine-1-carboxamide;

(2S,3R)—N-ethyl-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-5-yl)piperidine-1-carboxamide;

methyl (CIS)-3-(4-methyl-1H-pyrazol-3-yl)-2-(((1-(pyrimidin-2-yl)piperidin-4-yl)oxy)methyl)piperidine-1-carboxylate;

methyl (CIS)-2-(((1-(5-fluoropyrimidin-2-yl)piperidin-4-yl)oxy)methyl)-3-(4-methyl-1H-pyrazol-3-yl)piperidine-1-carboxylate;

methyl (CIS)-3-(4-methyl-1H-pyrazol-3-yl)-2-(((1-phenylpiperidin-4-yl)oxy)-methyl)piperidine-1-carboxylate;

isopropyl (CIS)-3-(4-methyl-1H-pyrazol-3-yl)-2-(((1-(pyrimidin-2-yl)piperidin-4-yl)oxy)methyl)piperidine-1-carboxylate;

(CIS)-N-ethyl-2-((((CIS)-4-(3-fluorophenyl)cyclohexyl)oxy)methyl)-3-(4-methyl-1H-pyrazol-3-yl)piperidine-1-carboxamide;

(2R,3S)—N-ethyl-2-((((CIS)-4-(3-fluorophenyl)cyclohexyl)oxy)methyl)-3-(4-methyl-1H-pyrazol-3-yl)piperidine-1-carboxamide;

(2S,3R)—N-ethyl-2-((((CIS)-4-(3-fluorophenyl)cyclohexyl)oxy)methyl)-3-(4-methyl-1H-pyrazol-3-yl)piperidine-1-carboxamide;

methyl (CIS)-2-((((S)-3′-fluoro-2,3,4,5-tetrahydro-[1,1′-biphenyl]-4-yl)oxy)methyl)-3-(4-methyl-1H-pyrazol-3-yl)piperidine-1-carboxylate;

cyclopropyl((CIS)-2-((((CIS)-4-(3-fluorophenyl)cyclohexyl)oxy)methyl)-3-(4-methyl-1H-pyrazol-3-yl)piperidin-1-yl)methanone;

methyl (CIS)-2-((((CIS)-4-(3-fluorophenyl)cyclohexyl)oxy)methyl)-3-(4-methyl-1H-pyrazol-3-yl)piperidine-1-carboxylate;

2,2-difluoroethyl (CIS)-2-((((CIS)-4-(3-fluorophenyl)cyclohexyl)oxy)methyl)-3-(4-methyl-1H-pyrazol-3-yl)piperidine-1-carboxylate;

(2R,3S)—N-ethyl-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-I-carboxamide;

(CIS)-N-ethyl-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-I-carboxamide;

(2S,3R)—N-ethyl-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-I-carboxamide;

cyclopropyl((CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

methyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-I-carboxylate;

(CIS)-N-ethyl-3-(1-methyl-1H-pyrazol-5-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)methyl)-piperidine-I-carboxamide;

methyl (CIS)-3-(4-methyl-1H-pyrazol-5-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)methyl)-piperidine-I-carboxylate;

2,2-difluoroethyl (CIS)-3-(4-methyl-1H-pyrazol-5-yl)-2-((((CIS)-4-phenyl-cyclohexyl)oxy)methyl)-piperidine-I-carboxylate;

methyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(4-(trifluoromethyl)-1H-pyrazol-5-yl)piperidine-I-carboxylate;

methyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-1,2,4-triazol-5-yl)piperidine-I-carboxylate;

(CIS)-N-ethyl-3-(1-methyl-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)-methyl)piperidine-I-carboxamide;

(CIS)-N-ethyl-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)pyrrolidine-I-carboxamide;

methyl 3-(1H-pyrazol-5-yl)-2-((((CIS)-4-(2,3,6-trifluorophenyl)cyclohexyl)-oxy)methyl)piperidine-1-carboxylate;

2-fluoroethyl 3-(1H-pyrazol-5-yl)-2-((((CIS)-4-(2,3,6-trifluorophenyl)-cyclohexyl)oxy)methyl)piperidine-1-carboxylate;

2,2,2-trifluoroethyl 3-(1H-pyrazol-5-yl)-2-((((CIS)-4-(2,3,6-trifluorophenyl)-cyclohexyl)oxy)methyl)piperidine-1-carboxylate;

1-(3-(1H-pyrazol-5-yl)-2-((((CIS)-4-(2,3,6-trifluorophenyl)cyclohexyl)-oxy)methyl)piperidin-1-yl)-2-hydroxyethan-1-one;

N-ethyl-2-((((CIS)-4-(2,3,6-trifluorophenyl)cyclohexyl)oxy)methyl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)piperidine-1-carboxamide;

3-(1H-pyrazol-5-yl)-N-(2,2,2-trifluoroethyl)-2-((((CIS)-4-(2,3,6-trifluorophenyl)cyclohexyl)-oxy)methyl)piperidine-1-carboxamide;

2,2-difluoroethyl 3-(1H-pyrazol-5-yl)-2-((((CIS)-4-(2,3,6-trifluorophenyl)-cyclohexyl)oxy)methyl)piperidine-1-carboxylate;

methyl (2R,5R)-5-methyl-3-(4-methyl-1H-pyrazol-5-yl)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)pyrrolidine-1-carboxylate;

methyl (2R,5R)-5-methyl-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-5-yl)pyrrolidine-1-carboxylate;

N-ethyl-2-(((4-isopropylcyclohexyl)oxy)methyl)-6-methyl-3-(1H-pyrazol-5-yl)piperidine-1-carboxamide;

(+/−) methyl (2R,3S,5S)-5-methyl-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-5-yl)piperidine-1-carboxylate;

(+/−) methyl (2R,3R,5S)-5-methyl-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-5-yl)piperidine-1-carboxylate;

(+/−) methyl (2R,3S,5R)-5-methyl-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-5-yl)piperidine-1-carboxylate;

methyl cis-3-(4-iodo-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)methyl)piperidine-1-carboxylate;

methyl (2R,3S)-3-(4-ethyl-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)methyl)-piperidine-1-carboxylate;

(2S,3R)-3-(4-ethyl-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)methyl)piperidine-1-carboxylate;

methyl (2R,3S)-3-(4-chloro-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)methyl)-piperidine-1-carboxylate;

methyl (2S,3R)-3-(4-chloro-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)methyl)-piperidine-1-carboxylate;

methyl cis-3-(4-chloro-1H-pyrazol-3-yl)-2-((((CIS)-4-(2-chlorophenyl)-cyclohexyl)oxy)methyl)-piperidine-1-carboxylate;

methyl cis-3-(4-chloro-1H-pyrazol-3-yl)-2-((((CIS)-4-(4-chlorophenyl)-cyclohexyl)oxy)methyl)-piperidine-1-carboxylate;

methyl (2R,3S)-3-(4-isopropyl-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)-methyl)piperidine-1-carboxylate;

methyl (2S,3R)-3-(4-isopropyl-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)methyl)-piperidine-1-carboxylate;

methyl (2R,3S)-3-(4-cyano-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)methyl)-piperidine-1-carboxylate;

methyl (2S,3R)-3-(4-cyano-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)-oxy)methyl)-piperidine-1-carboxylate;

methyl (2R,3S)-3-(4-(hydroxymethyl)-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)oxy)-methyl)piperidine-1-carboxylate;

methyl (2S,3R)-3-(4-(hydroxymethyl)-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-piperidine-1-carboxylate;

methyl (2R,3S)-3-(4-(difluoromethyl)-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-piperidine-1-carboxylate;

methyl (2S,3R)-3-(4-(difluoromethyl)-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl) piperidine-1-carboxylate;

methyl cis-3-(4-(methoxymethyl)-1H-pyrazol-3-yl)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-piperidine-1-carboxylate;

N-ethyl-2-(((4-isopropylcyclohexyl)oxy)methyl)-3-(4-methyl-1H-pyrazol-5-yl)piperidine-1-carboxamide;

N-ethyl-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-1,2,4-triazol-3-yl)piperidine-1-carboxamide;

methyl (CIS)-3-(6-hydroxypyridin-2-yl)-2-((((CIS)-4-phenylcyclohexyl)oxy)-methyl)piperidine-1-carboxylate;

methyl (CIS)-3-(2-hydroxythiazol-4-yl)-2-((((CIS)-4-phenylcyclohexyl)oxy)-methyl)piperidine-1-carboxylate;

methyl (CIS)-3-(6-hydroxy-3-methylpyridin-2-yl)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)piperidine-1-carboxylate;

methyl 3-(5-chloro-2-hydroxythiazol-4-yl)-2-(((4-phenylcyclohexyl)oxy)methyl)-piperidine-1-carboxylate;

((CIS)-2-methylcyclopropyl)((2R,3 S)-2-((((1s,4S)-4-phenylcyclohexyl)oxy-)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

((TRANS)-2-methylcyclopropyl)((CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)-methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

cyclopropyl((CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

(S)-2-amino-1-((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)-4-methoxybutan-1-one;

1-((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)-2-methylpropan-1-one;

2-(oxetan-3-yl)-1-((CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)ethan-1-one;

cyclopropyl((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)(2-methylcyclopropyl)methanone;

2-hydroxy-2-methyl-1-((CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)propan-1-one;

(1-hydroxycyclopropyl)((CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

cyclobutyl((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

(1-methylcyclopropyl)((CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

(2,2-dimethylcyclopropyl)((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

1-((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)propan-1-one;

cyclopentyl((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

1-((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)but-3-en-1-one;

1-((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)pent-4-yn-1-one;

1-((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)hex-5-yn-1-one;

2-methoxy-2-methyl-1-((CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)propan-1-one;

3-cyclopropyl-1-((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)propan-1-one;

(S)-2-fluoro-1-((CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)-2-methylpentan-1-one;

5-((CIS)-1-((TRANS)-2-ethylcyclopropane-1-carbonyl)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)piperidin-3-yl)-1H-pyrazol-2-ium;

((R)-2,2-dimethylcyclopropyl)((CIS)-2-((((CIS)-4-phenylcyclohexyl)-oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

(2,2-difluorocyclopropyl)((CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidin-1-yl)methanone;

2-chlorobenzyl (CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

((R)-4-methyl-5-oxomorpholin-2-yl)methyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

prop-2-yn-1-yl (CIS)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

2,2-difluoroethyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

2-oxopropyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

2-methoxy-2-oxoethyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

1,1-difluoropropan-2-yl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

prop-2-yn-1-yl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

pyridin-3-yl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

2,2,2-trifluoroethyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

but-2-yn-1-yl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

cyclobutylmethyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

isobutyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

pent-3-yn-1-yl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

(S)-2-methylbutyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

(R)-sec-butyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

(5-methyloxazol-2-yl)methyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

2,2-difluoropropyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

2-fluoroethyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

cyclobutyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

1,3-difluoropropan-2-yl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

3-methoxy-3-oxopropyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

(S)-but-3-yn-2-yl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

(S)-sec-butyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

cyclopentyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

3-methoxypropyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

(S)-2-methoxypropyl (CIS)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxylate;

(CIS)-N-allyl-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxamide;

(CIS)-N-isopropyl-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxamide;

(CIS)-N-benzyl-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxamide;

(CIS)-N-(cyclohexylmethyl)-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxamide;

(CIS)-N-cyclohexyl-2-((((CIS)-4-isopropylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxamide;

(CIS)-N-(cyclobutylmethyl)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxamide;

(CIS)-N-(1-methoxypropan-2-yl)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxamide;

(CIS)-N-(oxetan-3-yl)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxamide; and

(CIS)-N—((R)-sec-butyl)-2-((((CIS)-4-phenylcyclohexyl)oxy)methyl)-3-(1H-pyrazol-3-yl)piperidine-1-carboxamide;

or a pharmaceutically acceptable salt thereof.

11 . A pharmaceutical composition which comprises an inert carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.

12 . A method for treating narcolepsy in a mammalian subject which comprises administering to the patient an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

13 . A method for treating hypersomnia in a mammalian subject which comprises administering to the patient an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

Assignments (2)

Continuity (2)

References Cited (11)