IP Library Granted Patent US 9,840,481
Granted Patent B2
US 9,840,481 · App. 15/463,336 · Granted Dec 12, 2017

Allosteric modulators of nicotinic acetylcholine receptors

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Quick Facts
Patent No.
US 9,840,481
App. No.
15/463,336
Granted
Dec 12, 2017
Kind
B2
Abstract

The present disclosure relates to compounds of formula I that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation

Claims (336)

1. A compound having the formula I:

or a pharmaceutically acceptable salt thereof, wherein:

X is selected from

Y is 4 substituents, each independently selected from H, (C 1 -C 4 )alkyl, halogen, and OH, wherein said alkyl is optionally substituted with one or more halogen or OH;

A is a 5-membered heteroaryl ring which is substituted with 1 to 3 R groups each independently selected from OH, oxo, NR 7 R 8 , CN, alkoxy, halogen, aminoalkyl, hydroxyalkyl, alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, wherein said alkoxy, aminoalkyl, hydroxyalkyl, alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl are optionally substituted with one or more substituents independently selected from F, Cl, Br, OH, oxo, CF 3 , OCF 3 , CN, (C 1 -C 6 )alkyl, O(C 1 -C 4 )alkyl, S(C 1 -C 4 )alkyl, C═O(C 1 -C 4 )alkyl, (C═O)NR 7 R 8 , (C═O)OR 7 , (C 2 -C 4 )alkynyl, (C 3 -C 6 )cycloalkyl, O(C 3 -C 6 )cycloalkyl, C═O(C 3 -C 6 )cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein said alkyl, aryl, heteroaryl and heterocyclyl are optionally independently substituted with one or more halogen, CF 3 , OH and oxo;

R 1 is H or (C 1 -C 4 )alkyl;

R 2 is H or (C 1 -C 4 )alkyl;

R 3 is H, halogen or (C 1 -C 4 )alkyl, wherein said alkyl is optionally substituted with one or more halogen;

R 4 is H, halogen or (C 1 -C 4 )alkyl, wherein said alkyl is optionally substituted with one or more halogen;

or, R 3 and R 4 optionally can come to together to form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl ring wherein said ring may be optionally substituted with one or more substituents independently selected from OH, halogen, or (C 1 -C 4 )alkyl;

R 5 is H or (C 1 -C 4 )alkyl;

R 6 is H or (C 1 -C 4 )alkyl;

R 7 is H or (C 1 -C 4 )alkyl;

R 8 is H or (C 1 -C 4 )alkyl; and

R a is H or (C 1 -C 4 )alkyl.

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

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein Y is H.

4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein A is selected from

each substituted with 1 to 3 R groups independently selected from (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein each are optionally substituted with one or more substituents independently selected from F, Cl, Br, OH, oxo, CF 3 , OCF 3 , CN, (C 1 -C 4 )alkyl, O(C 1 -C 4 )alkyl, S(C 1 -C 4 )alkyl, C═O(C 1 -C 4 )alkyl, (C 2 -C 4 )alkynyl, (C 3 -C 6 )cycloalkyl, O(C 3 -C 6 )cycloalkyl, C═O(C 3 -C 6 )cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein said alkyl, aryl, heteroaryl and heterocyclyl are optionally independently substituted with one or more F, Cl, CF 3 , OH and oxo.

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 5 and R 6 are independently H or methyl.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 3 and R 4 are independently H, F or methyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having the formula:

wherein;

A is selected from

each substituted with 1 to 2 R groups independently selected from (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein each are optionally substituted with one or more substituents independently selected from F, Cl, Br, OH, oxo, CF 3 , OCF 3 , CN, (C 1 -C 4 )alkyl, O(C 1 -C 4 )alkyl, S(C 1 -C 4 )alkyl, C═O(C 1 -C 4 )alkyl, (C 2 -C 4 )alkynyl, (C 3 -C 6 )cycloalkyl, O(C 3 -C 6 )cycloalkyl, C═O(C 3 -C 6 )cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein said alkyl, aryl, heteroaryl and heterocyclyl are optionally independently substituted with one or more F, Cl, CF 3 , OH and oxo;

R 3 and R 4 are independently H, F or methyl; and

R 5 and R 6 are independently H or methyl.

8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, having the formula:

wherein;

A is selected from

each substituted with 1 to 2 R groups independently selected from (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, phenyl, indanyl, piperidinyl, pyridinyl, furanyl, oxazolyl, benzoxazinyl, cyclopentalpyrrolyl, thienopyrrolyl, thiazolyl, imidazolyl, azetidinyl, pyrrolyl, pyrazinyl, quinolinyl and benzothiazolyl wherein each are optionally substituted with one or more substituents independently selected from F, Cl, Br, OH, oxo, CF 3 , OCF 3 , CN, (C 1 -C 4 )alkyl, O(C 1 -C 4 )alkyl, S(C 1 -C 4 )alkyl, C═O(C 1 -C 4 )alkyl, (C 2 -C 4 )alkynyl, (C 3 -C 6 )cycloalkyl, O(C 3 -C 6 )cycloalkyl, C═O(C 3 -C 6 )cycloalkyl, phenyl, O-phenyl, imidazolyl, pyrazinyl, furanyl, oxazolidinyl, pyrrolidinyl, and benzoxazolyl, wherein said alkyl, phenyl, oxazolidinyl, pyrrolidinyl, and benzoxazolyl are optionally independently substituted with one or more F, Cl, CF 3 and oxo; and

R 3 and R 4 are independently H, F or methyl; and

R 5 and R 6 are independently H or methyl.

9. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein;

R is selected from (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, phenyl, indanyl, piperidinyl, pyridinyl, furanyl, oxazolyl, benzoxazinyl, cyclopentalpyrrolyl, thienopyrrolyl, thiazolyl, imidazolyl, azetidinyl, pyrrolyl, pyrazinyl, quinolinyl and benzothiazolyl wherein each are optionally substituted with one or more substituents independently selected from F, Cl, Br, OH, oxo, CF 3 , OCF 3 , CN, (C 1 -C 4 )alkyl, O(C 1 -C 4 )alkyl, S(C 1 -C 4 )alkyl, C═O(C 1 -C 4 )alkyl, (C 2 -C 4 )alkynyl, (C 3 -C 6 )cycloalkyl, O(C 3 -C 6 )cycloalkyl, C═O(C 3 -C 6 )cycloalkyl, phenyl, O-phenyl, imidazolyl, pyrazinyl, furanyl, oxazolidinyl, pyrrolidinyl, and benzoxazolyl, wherein said alkyl, phenyl, oxazolidinyl, pyrrolidinyl, and benzoxazolyl are optionally independently substituted with one or more F, Cl, CF 3 and oxo;

R 3 and R 4 are independently H, F or methyl; and

R 5 and R 6 are independently H or methyl.

10. The compound of claim 1 which is selected from the group consisting of

4-((1S,3S)-3-(3-(5-Fluoro-2-methylphenyl)-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl)-benzenesulfonamide;

4-((1S,3S)-3-(5-(2-Cyclopropylethyl)-1,2,4-oxadiazol-3-yl)-2,2-dimethylcyclopropyl)benzenesulfonamide;

4-((1S,3S)-2,2-Dimethyl-3-(5-(2,3,6-trifluorophenyl)-1,2,4-oxadiazol-3-yl)cyclopropyl) benzenesulfonamide;

4-((1R,2R)-2-(3-(3-Fluorophenyl)-1,2,4-oxadiazol-5-yl)cyclopropyl)benzenesulfonamide;

4-{(1R,3R)-3-[5-(2,4-Difluorophenyl)-1,3,4-thiadiazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(2,4-Difluorophenyl)-1,3,4-oxadiazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-2,2-Difluoro-3-[3-(propan-2-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-[(1R,2R)-2-(5-Phenyl-1,3-oxazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(4-Phenyl-1,3-oxazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,3R)-2,2-Dimethyl-3-(2-phenyl-1,3-oxazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,3R)-2,2-Dimethyl-3-(3-phenylisoxazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,3R)-2,2-Dimethyl-3-(1-phenyl-1H-1,2,3-triazol-4-yl)cyclopropyl]benzenesulfonamide;

4-{(1R,3R)-3-[1-(3-Fluorophenyl)-1H-pyrazol-4-yl]-2,2-dimethylcyclopropyl}benzene sulfonamide;

4-{(1R,2R)-2-[4-(3-Fluorophenyl)-1,3-thiazol-2-yl]cyclopropyl}benzene sulfonamide;

4-[(1R,2R)-2-(5-Methyl-4-phenyl-1,3-thiazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(4-Methyl-5-phenyl-1,3-thiazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-(5-phenyl-1,3-thiazol-2-yl)cyclopropyl]benzenesulfonamide;

4-{trans-2-[3-(Propan-2-yl)-1,2,4-thiadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(5-Chloro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzene sulfonamide;

4-((1R,3R)-3-(3-Cyclohexyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl)benzene sulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(propan-2-yl)-1,3-thiazol-2-yl]cyclopropyl}benzenesulfonamide;

4-(2-Methyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl)benzenesulfonamide;

4-{(1R,2R)-2-[1-(3-Fluorobenzyl)-1H-pyrazol-3-yl]cyclopropyl}benzenesulfonamide;

4-[trans-2-(2-Phenyl-1,3-oxazol-4-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(2-Phenyl-1,3-thiazol-4-yl)cyclopropyl]benzenesulfonamide;

4-{(1R,2R)-2-[1-(3-Fluorophenyl)-1H-1,2,3-triazol-4-yl]cyclopropyl}benzenesulfonamide;

4-[(1R,2R)-2-(2-Phenyl-1,3-thiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(2-Cyclohexyl-1,3-oxazol-5-yl)cyclopropyl]benzenesulfonamide;

4-{(1R,2R)-2-[5-(Piperidin-1-yl)-1,2,4-thiadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-[trans-2,2-Dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]phenyl sulfamate;

4-[(1R,3R)-3-(4,5-Dicyclopropyl-1,3-oxazol-2-yl)-2,2-dimethylcyclopropyl]benzene sulfonamide;

4-[trans-2,2-Dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-2-fluorobenzenesulfonamide;

5-{trans-2,2-Dimethyl-3-[4-(methylsulfonyl)phenyl]cyclopropyl}-3-phenyl-1,2,4-oxadiazole;

4-[trans-3-(5-Cyclopentylisoxazol-3-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-{(1S,3S)-3-[2-(3-Fluorophenyl)-1-methyl-1H-imidazol-4-yl]-2,2-dimethylcyclopropyl}benzene sulfonamide;

4-{trans-2,2-Dichloro-3-[3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzene sulfonamide;

4-{(1R,2R)-2-[5-(Piperidin-1-yl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide

4-[trans-2,2-Dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-3-methylbenzenesulfonamide

4-{(1R,3R)-3-[3-(5-Chloro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1R,3R)-3-{3-[4-Fluoro-2-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-[(1R,3R)-2,2-Dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,3R)-3-{3-[5-Chloro-2-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-5-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-[(1S,2S)-2-(3-Phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-{(1R,3R)-3-[3-(5-Fluoro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1R,3R)-3-[3-(2,4-Difluorophenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,2S)-2-[3-(2,4-Difluorophenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-2,2-Difluoro-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-{(1R,3R)-3-[3-(3-Fluorophenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1R,3R)-3-[3-(2,6-Difluorophenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1R,3R)-3-[3-(2-Fluorophenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1R,3R)-2,2-Dimethyl-3-{3-[2-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzenesulfonamide;

4-{(1R,3R)-3-[3-(3-Bromophenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,2S)-2-[3-(5-Chloro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,3R)-2,2-Dimethyl-3-[3-(propan-2-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,3R)-3-[3-(5-Fluoropyridin-3-yl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1R,3R)-3-(3-Cyclobutyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1S,2S)-2-(3-Cyclohexyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-{(1S,2S)-2-[3-(5-Fluoropyridin-3-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,2S)-2-[3-(2-Methylpyridin-3-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-[(1R,3R)-2,2-Dimethyl-3-{3-[5-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzene sulfonamide;

4-{(1R,3R)-3-[3-(3,3-Difluorocyclobutyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1R,3R)-3-(3-Cyclopentyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]benzene sulfonamide;

4-{(1R,3R)-3-[3-(Cyclopropylmethyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1R,3R)-2,2-Dimethyl-3-[3-(tetrahydrofuran-3-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,3R)-2,2-Dimethyl-3-[3-(tetrahydrofuran-2-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,3R)-2,2-Dimethyl-3-[3-(1-phenylcyclopropyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,3R)-3-[3-(5-Fluoro-2,3-dihydro-1H-inden-1-yl)-1,2,4-oxadiazol-5-yl]-2,2-dimethyl cyclopropyl}benzenesulfonamide;

4-{(1R,3R)-2,2-Dimethyl-3-[3-(spiro[3.3]hept-2-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,3R)-3-[3-(1-Acetylpiperidin-4-yl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzene sulfonamide;

4-[(1S,3S)-3-(3-tert-Butyl-1,2,4-oxadiazol-5-yl)-2,2-difluorocyclopropyl]benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-3-(3-Cyclopentyl-1,2,4-oxadiazol-5-yl)-2,2-difluorocyclopropyl]benzenesulfonamide;

4-{(1S,3S)-3-[3-(5-Chloro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-{3-[4-Fluoro-2-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-[(1S,3S)-3-{3-[5-Chloro-2-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-5-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(3-Phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-{3-[2-(Trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-{3-[4-Fluoro-2-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-{3-[5-Fluoro-2-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzenesulfonamide;

4-{(1R,2R)-2-[3-(2,6-Difluorophenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(3-Bromophenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(2-Fluoro-6-methylphenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[3-(2,4-Difluorophenyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(2,4-Difluorophenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(4-Fluorophenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(2,3-Difluorophenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(2,5-Difluorophenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(2-Methylphenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(3-Methylphenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzene sulfonamide;

4-{(1R,2R)-2-[3-(4-Methylphenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(2-Fluorophenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-[(1R,3R)-2,2-Difluoro-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-{(1R,3R)-2,2-Difluoro-3-[3-(propan-2-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{3-[4-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzene sulfonamide;

4-[(1S,3S)-3-(3-Cyclohexyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[3-(pyridin-2-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[3-(propan-2-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[3-(5-Fluoropyridin-3-yl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-(3-Cyclobutyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(3-Cyclohexyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-3-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]benzene sulfonamide;

4-[(1S,3S)-3-(3-tert-Butyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-{(1R,2R)-2-[3-(Propan-2-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(5-Fluoropyridin-3-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[3-(2-methylpyridin-3-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(2-Methylpyridin-3-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{3-[5-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzene sulfonamide;

4-{(1S,3S)-3-[3-(3,3-Difluorocyclobutyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(3,3-Difluorocyclobutyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-(3-Cyclopentyl-1,2,4-oxadiazol-5-yl)-2,2-dimethylcyclopropyl]benzene sulfonamide;

4-[(1R,2R)-2-(3-Cyclopentyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-{3-[5-(Trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzenesulfonamide;

4-{(1R,2R)-2-[3-(1-Phenylcyclopropyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(2-Cyclopropylpyridin-3-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-[(1R,2R)-2-{3-[4-(Trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzenesulfonamide;

4-{(1R,2R)-2-[3-(2,4-Difluorobenzyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[3-(Cyclopropylmethyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1R,2R)-2-[3-(Cyclopropylmethyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{3-[6-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzene sulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{3-[2-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzene sulfonamide;

4-{(1R,2R)-2-[3-(4-Methyl-1,3-oxazol-5-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[3-(2-Hydroxycyclohexyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylcyclopropyl}benzene sulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{3-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl}cyclopropyl]benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[3-(1-methylcyclohexyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,3R)-2,2-Difluoro-3-[3-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{trans-2-[3-(5-Chloro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-{trans-3-[3-(5-Chloro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-2,2-difluorocyclopropyl}benzenesulfonamide;

4-{2-[3-(2,4-Difluorophenyl)-1,2,4-oxadiazol-5-yl]-2-methylcyclopropyl}benzenesulfonamide;

4-{2-[3-(2,4-Difluorophenyl)-1,2,4-oxadiazol-5-yl]-1-methylcyclopropyl}benzenesulfonamide;

4-{(1R,3R)-3-[5-(2,6-Difluorophenyl)-1,3,4-oxadiazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1R,3R)-3-{5-[5-Fluoro-2-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-[(1R,3R)-3-{5-[2-Fluoro-6-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-[(1R,3R)-2,2-Dimethyl-3-(5-phenyl-1,3,4-thiadiazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,3R)-2,2-Dimethyl-3-(5-phenyl-1H-1,2,4-triazol-3-yl)cyclopropyl]benzenesulfonamide;

4-{(1R,3R)-3-[5-(2-Cyclopropylpyridin-3-yl)-1,3,4-oxadiazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1R,3R)-3-(5-Cyclohexyl-1,3,4-thiadiazol-2-yl)-2,2-dimethylcyclopropyl]benzene sulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{5-[3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl}cyclopropyl]benzenesulfonamide;

4-{(1S,3S)-3-[5-(3-Fluorophenyl)-1,3,4-oxadiazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{5-[2-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl}cyclopropyl]benzenesulfonamide;

4-{(1S,3S)-3-[5-(2,6-Difluorophenyl)-1,3,4-oxadiazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-{5-[5-Fluoro-2-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-(5-phenyl-1,3,4-thiadiazol-2-yl)cyclopropyl]benzenesulfonamide;

4-{(1S,3S)-3-[5-(2,4-Difluorophenyl)-1,3,4-thiadiazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(propan-2-yl)-1,3,4-oxadiazol-2-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-(5-Cyclopentyl-1,3,4-oxadiazol-2-yl)-2,2-dimethylcyclopropyl]benzene sulfonamide;

4-{(1S,3S)-3-[5-(Cyclopropylmethyl)-1,3,4-oxadiazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(2-Cyclopropylpyridin-3-yl)-1,3,4-oxadiazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-(5-Cyclohexyl-1,3,4-thiadiazol-2-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1S,3S)-3-(5-Cyclopentyl-1,3,4-thiadiazol-2-yl)-2,2-dimethylcyclopropyl]benzene sulfonamide;

4-[(1S,3S)-3-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)-2,2-dimethylcyclopropyl]benzene sulfonamide;

4-[(1R,2R)-2-(5-Cyclopentyl-1,3,4-thiadiazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-3-{5-[2-Fluoro-6-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-(5-phenyl-1,2,4-oxadiazol-3-yl)cyclopropyl]benzenesulfonamide;

4-{(1S,3S)-3-[5-(2-Chloro-4-fluorophenyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(2,4,6-trifluorophenyl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-{5-[4-Fluoro-3-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-{(1S,3S)-3-[5-(3-Fluorophenyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(2-Fluoro-6-methylphenyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-{5-[2-Fluoro-5-(2-oxo-1,3-oxazolidin-3-yl)phenyl]-1,2,4-oxadiazol-3-yl}-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-{(1S,3S)-3-[5-(2,6-Difluorophenyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(3-Cyclopropylphenyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(2,3,5-trifluorophenyl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(4-Ethynylphenyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(4-Cyanophenyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{5-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl}cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{5-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-1,2,4-oxadiazol-3-yl}cyclopropyl]benzenesulfonamide;

4-{(1R,2R)-2-[5-(3-Fluorophenyl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(2,4-Difluorobenzyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-{5-[1-(3-Chlorophenoxy)ethyl]-1,2,4-oxadiazol-3-yl}-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-{(1S,3S)-3-[5-(5-Fluoro-2,3-dihydro-1H-inden-1-yl)-1,2,4-oxadiazol-3-yl]-2,2-dimethyl cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-{5-[1-(2,5-Difluorophenyl)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-[(1S,3S)-3-{5-[(5-Chloro-2-oxo-1,3-benzoxazol-3 (2H)-yl)methyl]-1,2,4-oxadiazol-3-yl}-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(1,3-thiazol-4-yl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(4-methyl-1,3-oxazol-5-yl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(2-Cyclopropyl-1H-imidazol-4-yl)-1,2,4-oxadiazol-3-yl]-2,2-dimethyl cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(1-Cyclopropylpiperidin-4-yl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(1-methyl-H-pyrrol-3-yl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-{5-[1-(1H-Imidazol-1-yl)ethyl]-1,2,4-oxadiazol-3-yl}-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{5-[1-(pyrazin-2-yl)cyclopropyl]-1,2,4-oxadiazol-3-yl}cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{5-[4-(trifluoromethyl)quinolin-2-yl]-1,2,4-oxadiazol-3-yl}cyclopropyl]benzene sulfonamide;

4-[(1S,3S)-3-{5-[6-(2-Fluoroethoxy)pyridin-3-yl]-1,2,4-oxadiazol-3-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(tetrahydrofuran-2-ylmethyl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(1,1-Difluoroethyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-{5-[4-(4-Fluorophenyl)-1H-imidazol-2-yl]-1,2,4-oxadiazol-3-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-(5-{2-[(2,2,2-trifluoroethyl)sulfanyl]-1,3-oxazol-5-yl}-1,2,4-oxadiazol-3-yl)cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{5-[3-(trifluoromethyl)pyridin-4-yl]-1,2,4-oxadiazol-3-yl}cyclopropyl]benzene sulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{5-[4-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-3-yl}cyclopropyl]benzene sulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-{5-[2-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-3-yl}cyclopropyl]benzene sulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(4H-thieno[3,2-b]pyrrol-5-yl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-{5-[1-(Cyclopropylcarbonyl)azetidin-3-yl]-1,2,4-oxadiazol-3-yl}-2,2-dimethyl cyclopropyl]benzene sulfonamide;

4-{(1S,3S)-3-[5-(2-Cyclopentyl-1-oxooctahydrocyclopenta[c]pyrrol-5-yl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzene sulfonamide;

4-[(1S,3S)-3-(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1S,3S)-3-(5-Cyclopentyl-1,2,4-oxadiazol-3-yl)-2,2-dimethylcyclopropyl]benzene sulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(spiro[2.5]oct-4-yl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(2,2,2-trifluoro-1-hydroxyethyl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(4-Hydroxycyclohexyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(3-Hydroxycyclobutyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[5-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-8-yl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[5-(2-Hydroxy-1,3-benzothiazol-6-yl)-1,2,4-oxadiazol-3-yl]-2,2-dimethyl cyclopropyl}benzenesulfonamide;

4-{(1R,3R)-3-[5-(2-Cyclopropylethyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1R,2R)-2-(5-Cyclohexyl-1,2,4-oxadiazol-3-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-{5-[1-(Trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl}cyclopropyl]benzenesulfonamide;

4-{(1R,2R)-2-[5-(5-Fluoropyridin-3-yl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-{(1R,3R)-3-[4-(2-Fluorophenyl)-1,3-oxazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1R,3R)-3-[4-(2,4-Difluorophenyl)-1,3-oxazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1R,3R)-3-[4-(2,5-Difluorophenyl)-1,3-oxazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1R,3R)-3-(4-tert-Butyl-1,3-oxazol-2-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1R,3R)-3-(4-Cyclopropyl-1,3-oxazol-2-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1S,2S)-2-(4-Phenyl-1,3-oxazol-2-yl)cyclopropyl]benzenesulfonamide;

4-{(1S,2S)-2-[4-(3-Fluorophenyl)-1,3-thiazol-2-yl]cyclopropyl}benzenesulfonamide;

4-[(1R,3R)-3-(4-Cyclopentyl-1,3-oxazol-2-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1R,3R)-3-(5-Cyclopentyl-1,3-thiazol-2-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-{(1S,2S)-2-[5-(3-Fluorophenyl)-1,3-thiazol-2-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-3-(5-Cyclopentyl-1,3-oxazol-2-yl)-2,2-difluorocyclopropyl]benzenesulfonamide; 4-{(1S,3S)-3-[4-(2-Fluorophenyl)-1,3-oxazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[4-(2,5-Difluorophenyl)-1,3-oxazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[4-(2,4-Difluorophenyl)-1,3-oxazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1R,2R)-2-(5-tert-Butyl-1,3-oxazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(5-Cyclopropyl-1,3-oxazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(4-Ethyl-1,3-oxazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-3-(4-tert-Butyl-1,3-oxazol-2-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1S,3S)-3-(4-Ethyl-1,3-oxazol-2-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(4-Phenyl-1,3-thiazol-2-yl)cyclopropyl]benzenesulfonamide;

4-{(1S,3S)-3-[4-(3-Fluorophenyl)-1,3-thiazol-2-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-2,2-Dimethyl-3-[4-(propan-2-yl)-1,3-thiazol-2-yl]cyclopropyl}benzenesulfonamide;

4-[(1R,2R)-2-(4-Phenyl-1H-imidazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,3R)-3-(5-Cyclopentyl-1,3-oxazol-2-yl)-2,2-difluorocyclopropyl]benzenesulfonamide;

4-[(1S,3S)-3-(5-Cyclopentyl-1,3-oxazol-2-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(5-Cyclopentyl-1,3-thiazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-3-(5-Cyclopentyl-1,3-thiazol-2-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1S,3S)-3-(4-Cyclopentyl-1,3-oxazol-2-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-{(1R,2R)-2-[5-(3-Fluorophenyl)-1,3-thiazol-2-yl]cyclopropyl}benzenesulfonamide;

4-[(1R,2R)-2-(4-Cyclopentyl-1,3-oxazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,3S)-3-(4-Cyclohexyl-1,3-thiazol-2-yl)-2,2-difluorocyclopropyl]benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-(2-phenyl-1,3-oxazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1S,2S)-2-(2-Phenyl-1,3-oxazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(2-Phenyl-1,3-oxazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-(3-phenylisoxazol-5-yl)cyclopropyl]benzenesulfonamide;

4-{(1R,3R)-3-[1-(3-Fluorophenyl)-1H-1,2,3-triazol-4-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-{(1S,3S)-3-[1-(3-Fluorophenyl)-1H-1,2,3-triazol-4-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1S,3S)-2,2-Dimethyl-3-(1-phenyl-1H-1,2,3-triazol-4-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,3R)-3-(1-Cyclopentyl-1H-pyrazol-4-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1R,3R)-3-(5-Ethoxy-1,2,4-thiadiazol-3-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-{(1R,2R)-2-[5-(3-Fluorophenyl)-1,2,4-thiadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-[(1R,2R)-2-(5-Cyclohexyl-1,2,4-thiadiazol-3-yl)cyclopropyl]benzenesulfonamide;

4-{(1S,3S)-2,2-Difluoro-3-[5-(piperidin-1-yl)-1,2,4-thiadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-[(1S,3S)-2,2-Difluoro-3-(5-phenyl-1,2,4-thiadiazol-3-yl)cyclopropyl]benzenesulfonamide;

4-[(1R,2R)-2-(2-Cyclopentyl-1,3-thiazol-4-yl)cyclopropyl]benzenesulfonamide;

4-[(1S,3S)-3-(2-Cyclopentyl-1,3-thiazol-4-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1R,3R)-3-(5-Cyclohexyl-1,2,4-oxadiazol-3-yl)-2,2-dimethylcyclopropyl]benzenesulfonamide;

4-[(1R,3R)-2,2-Dimethyl-3-(5-phenyl-1,2,4-oxadiazol-3-yl)cyclopropyl]benzenesulfonamide;

4-{(1R,3R)-3-[5-(3-Fluorophenyl)-1,2,4-oxadiazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[(1R,3R)-2,2-Dimethyl-3-{5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl}cyclopropyl]benzenesulfonamide;

4-{(1R,3R)-2,2-Dimethyl-3-[5-(piperidin-1-yl)-1,2,4-oxadiazol-3-yl]cyclopropyl}benzenesulfonamide;

4-[(1R,2R)-2-(2-Cyclopentyl-1,3-oxazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[(1S,2S)-2-(2-Phenyl-1,3-thiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[trans-2,2-Difluoro-3-(5-phenyl-1,3-oxazol-2-yl)cyclopropyl]benzenesulfonamide;

4-[2-Methyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-[trans-2-(3-Phenyl-1,2,4-oxadiazol-5-yl)spiro[2.4]hept-1-yl]benzenesulfonamide;

4-{trans-2-[3-(3-Fluorophenyl)-1,2,4-thiadiazol-5-yl]cyclopropyl}benzenesulfonamide;

4-[trans-2,2-Dichloro-3-(3-cyclopentyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

4-{trans-3-[5-(3-Fluorophenyl)isoxazol-3-yl]-2,2-dimethylcyclopropyl}benzenesulfonamide;

4-[trans-2,2-Dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-3-fluorobenzenesulfonamide;

4-[trans-2,2-Dimethyl-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-2-methylbenzenesulfonamide; and

4-[trans-2,2-Dichloro-3-(3-phenyl-1,2,4-oxadiazol-5-yl)cyclopropyl]benzenesulfonamide;

or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

12. The pharmaceutical composition of claim 11 , further comprising a second therapeutic agent selected from the group consisting of acetylcholinesterase inhibitors; NMDA receptor antagonists; antipsychotics; MAO-B inhibitors; and levodopa.

13. A method of treating a patient with cognitive impairments associated with Alzheimer's disease, Parkinson's disease, and schizophrenia, the method comprising administering to the patient the compound of claim 1 , or a pharmaceutically acceptable salt thereof, in an amount effective to treat the patient.

14. A compound which is

15. A pharmaceutically acceptable salt of a compound which is

16. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the compound of claim 14 .

17. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the pharmaceutically acceptable salt of claim 15 .

18. A method of treating a patient with mild to moderate dementia of the Alzheimer's type, the method comprising administering to the patient the compound of claim 14 in an amount effective to treat the patient.

19. A compound which is

20. A pharmaceutically acceptable salt of a compound which is

21. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the compound of claim 19 .

22. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the pharmaceutically acceptable salt of claim 20 .

23. A method of treating a patient with mild to moderate dementia of the Alzheimer's type, the method comprising administering to the patient the compound of claim 19 in an amount effective to treat the patient.

24. A compound which is

25. A pharmaceutically acceptable salt of a compound which is

26. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the compound of claim 24 .

27. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the pharmaceutically acceptable salt of claim 25 .

28. A method of treating a patient with mild to moderate dementia of the Alzheimer's type, the method comprising administering to the patient the compound of claim 24 in an amount effective to treat the patient.

29. A compound which is

30. A pharmaceutically acceptable salt of a compound which is

31. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the compound of claim 29 .

32. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the pharmaceutically acceptable salt of claim 30 .

33. A method of treating a patient with mild to moderate dementia of the Alzheimer's type, the method comprising administering to the patient the compound of claim 29 in an amount effective to treat the patient.

34. A compound which is

35. A pharmaceutically acceptable salt of a compound which is

36. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the compound of claim 34 .

37. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the pharmaceutically acceptable salt of claim 35 .

38. A method of treating a patient with mild to moderate dementia of the Alzheimer's type, the method comprising administering to the patient the compound of claim 34 in an amount effective to treat the patient.

Assignments (4)
MERGER Recorded Aug 8, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 061102/0145 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 20, 2017
From: HARVEY, ANDREW JOHN; HUFF, BELINDA C.
To: BIONOMICS LIMITED
Reel/Frame 041645/0426 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 20, 2017
From: BIONOMICS LIMITED
To: MERCK SHARP & DOHME CORP.
Reel/Frame 041645/0690 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 20, 2017
From: CROWLEY, BRENDAN M.; CAMPBELL, BRIAN T.; DUFFY, JOSEPH L.; GRESHOCK, THOMAS J.; GUIADEEN, DEODIAL G.; LEAVITT, KENNETH J.; RADA, VANESSA L.; SANDERS, JOHN M.; SHIPE, WILLIAM D.; SUEN, LINDA M.; BELL, IAN M.
To: MERCK SHARP & DOHME CORP.
Reel/Frame 041652/0470 →