IP Library Granted Patent US 8,044,069
Granted Patent B2
US 8,044,069 · App. 12/571,862 · Granted Oct 25, 2011

Compounds as calcium channel blockers

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Quick Facts
Patent No.
US 8,044,069
App. No.
12/571,862
Granted
Oct 25, 2011
Kind
B2
Abstract

The present application relates to calcium channel inhibitors containing compounds of formula (I) wherein Ar 1 , Ar 2 , L 1 , L 2 , n, R 1 , R 4 , X and Y are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.

Claims (432)

1. A compound of formula (I),

or a pharmaceutically acceptable salt thereof, wherein

 is a single or double bond;

n, at each occurrence, is independently 1 or 2;

X is CH 2 ;

r, at each occurrence, is independently 0, 1, or 2;

Ar 1 and Ar 2 are independently aryl or heteroaryl; wherein each Ar 1 and Ar 2 is independently unsubstituted or further substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, —CN, —NO 2 , —OR a , —S(R c ), —S(O)(R c ), —S(O) 2 R c , —S(O) 2 N(R b ) 2 , —C(O)R b , —C(O)O(R b ), —C(O)N(R b ) 2 , —N(R b ) 2 , —N(R b )C(O)R b , —N(R b )C(O)O(R b ), —N(R b )S(O) 2 R c , haloalkyl, —(CR d R e ) m —OR a , —(CR d R e ) m —S(R c ), —(CR d R e ) m —S(O)(R c ), —(CR d R e ) m —S(O) 2 R c , —(CR d R e ) m —S(O) 2 N(R b ) 2 , —(CR d R e ) m —C(O)R b , —(CR d R e ) m —C(O)O(R b ), —(CR d R e ) m —C(O)N(R b ) 2 , —(CR d R e ) m —N(R b ) 2 , —(CR d R e ) m —N(R b )C(O)R b , —(CR d R e ) m —N(R b )C(O)O(R b ), —(CR d R e ) m —N(R b )S(O) 2 R c , and —CH═CH-heteroaryl-(CR d R e ) m —O(alkyl);

R a , at each occurrence, is independently hydrogen, alkyl, haloalkyl, or —(CR d R e ) m —O(alkyl);

R b , at each occurrence, is independently hydrogen, alkyl, haloalkyl, or G 1 ;

R c , at each occurrence, is independently alkyl or haloalkyl;

R d and R e , at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;

m, at each occurrence, is independently 1, 2, 3, 4, 5, or 6;

L 1 is —(CH 2 ) p C(O)— or —(CH 2 ) p —; wherein

p, at each occurrence, is independently 1, 2, 3, or 4;

L 2 is —N(R 5 )—, —N(R 5 )—(CH 2 ) q —, —NH—CH(R 5 )—, —NH—CH(R 5 )—(CH 2 ) q —, —N(R 5 )—CH 2 CH(OH)CH 2 —, —N(R 5 )—CH(R 6 )—, (i), (iv), (v), (vi), (vii), (viii), (ix), (x), (xi) or (xii);

q, at each occurrence, is independently 1, 2, or 3;

w is 1, 2, 3, or 4;

x is 2, 3, 4, or 5;

y at each occurrence, is independently 1, 2, or 3;

z at each occurrence, is independently 0, 1, 2, or 3;

R 5 at each occurrence, is hydrogen, alkyl, or G 1 ;

R ii at each occurrence, is independently oxo or alkyl;

R iii is hydrogen, alkyl, or aryl;

R iv is hydrogen, aryl, OR a or part of double bond between L 2 and Y;

R vi is hydrogen or alkyl;

X 1 is CH 2 , NH, O, or a bond;

A 1 and A 3 are independently C or N;

A 2 , A 4 , and A 5 are each independently CH, CR 5 , N, O, or S;

one of A 6 , A 7 , A 8 , A 9 , and A 10 is C and the others are each independently CH or N;

Y is a bond, CR 2 R 3 , CH 2 CR 2 R 3 , CR 2 , CR 2 R 3 O, C(O), C(O)OCR 2 R 3 , N—O—CR 2 R 3 , O, or S(O) r ;

R 2 is hydrogen or G 1 ;

R 3 is hydrogen, alkyl, cycloalkyl, or hydroxyl; or

R 2 and R 3 taken together with the carbon atom to which they are attached form a cycloalkyl;

G 1 , at each occurrence, is independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl; wherein each G 1 is independently unsubstituted or further substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, oxo, —CN, —NO 2 , —OR a , —S(R c ), —S(O)(R c ), —S(O) 2 R c , haloalkyl, —(CR d R e ) m —OR a , —(CR d R e ) m —S(R c ), —(CR d R e ) m —S(O)(R c ), and —(CR d R e ) m —S(O) 2 R c ;

R 1 is hydrogen, alkyl, or G 1 ; and

R 4 is hydrogen; or

R 3 and R 5 taken together are —(CH 2 ) p — or —O—(CH 2 ) p —; or

R 4 and R 5 taken together are a bond, —(CH 2 ) s —, or —O—(CH 2 ) s —; wherein

s, at each occurrence, is independently 1 or 2; or

R 4 and R 6 taken together are —CH 2 —; or

L 1 -L 2 Y taken together are S(O) r ;

with the provisos that

Ar 2 is other than a pyrazole substituted with 1 or 2 groups independently selected from aryl and heteroaryl; or

when Ar 1 is aryl or heteroaryl, R 1 is aryl or heteroaryl, X is CH 2 , n is 1, L 1 is —(CH 2 ) p —, Y is CR 2 R 3 , Ar 2 is aryl, and R 4 is H, then L 2 is other than —N(R 5 )—, —N(R 5 )—(CH 2 ) q —, or —NH—CH(R 5 )—; or

when Ar 1 and R 1 are both unsubstituted phenyl, X is CH 2 , n is 2, L 1 is —CH 2 C(O)—, L 2 is —N(CH 3 )—(CH 2 ) 3 —, Y is CR 2 R 3 , Ar 2 is unsubstituted phenyl, and R 4 is hydrogen, then R 2 is other than unsubstituted phenyl; or

when Ar 1 is phenyl, R 1 is hydrogen or methyl, X is CH 2 , n is 1, L 1 -L 2 Y taken together are S(O) r , r is 2, then Ar 2 is other than 4-methylphenyl; or

when the bond connecting L 2 to Y is a double bond, Y is CR 2 ; or

when X is other than CH 2 , n is 2.

2. The compound according to claim 1 , wherein

n is 1;

X is CH 2 ;

Ar 1 is phenyl; and

R 1 is hydrogen or G 1 , wherein G 1 is phenyl;

wherein the phenyl groups of Ar 1 and R 1 are independently either unsubstituted or further substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, haloalkyl, and —OR a , wherein R a is alkyl.

3. The compound according to claim 2 , wherein

Ar 2 is oxazolyl, phenyl, pyridinyl, pyrazolyl, or thiazolyl either unsubstituted or further substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl, —CN, halogen, and haloalkyl;

L 1 is —(CH 2 ) p C(O)—;

L 2 is —N(R 5 )— or —N(R 5 )—(CH 2 ) q —;

R 5 is hydrogen;

q is 1 or 2;

Y is a bond or CR 2 R 3 ;

R 2 is hydrogen or G 1 , wherein G 1 is phenyl; and

R 3 is hydrogen, alkyl, or cycloalkyl; or

R 2 and R 3 taken together with the carbon atom to which they are attached form a cycloalkyl.

4. The compound according to claim 2 , wherein

Ar 2 is quinolinyl or phenyl, wherein phenyl is either unsubstituted or further substituted with 1, 2, or 3 substituents selected from the group consisting of —OR a and —CH═CH-heteroaryl-(CR d R e ) m —O(alkyl), wherein heteroaryl is isoxazolyl;

m is 1;

R a is alkyl;

R d and R e are each hydrogen;

L 1 is —(CH 2 ) p —;

p is 2;

L 2 is —N(R 5 )—, —N(R 5 )—(CH 2 ) q —, or —N(R 5 )—CH 2 CH(OH)CH 2 —;

q is 3; and

Y is O or C(O).

5. The compound according to claim 2 , wherein

Ar 2 is indolyl, phenyl or pyridyl either unsubstituted or further substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl, halogen, haloalkyl, and —OR a , wherein R a is alkyl;

L 1 is —(CH 2 ) p C(O)—;

L 2 is —N(R 5 )—, —N(R 5 )—(CH 2 ) q —, —NH—CH(R 5 )—(CH 2 ) q —, —NH—CH(R 5 )—, (i), (ii), (iii), (iv), (v), (vi), (vii), (viii), (ix), or (xii);

R 5 is hydrogen;

q is 1, 2, or 3;

Y is a bond, CR 2 , CH 2 CR 2 R 3 , or CR 2 R 3 ; and

R 2 is hydrogen or phenyl, wherein the phenyl is either unsubstituted or further substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl, halogen, and haloalkyl;

R 3 is hydrogen, alkyl, or hydroxyl; or

R 3 and R 5 taken together are —(CH 2 ) p —; wherein,

p, at each occurrence, is independently 1, 2, or 3; or

R 4 and R 5 taken together are a bond or —(CH 2 ) s —; wherein,

s is 1.

6. The compound according to claim 2 , wherein

Ar 2 is thiazolyl, phenyl, pyridyl, or pyrazinyl, wherein phenyl, pyridyl, pyrazinyl and thiazoyl are either unsubstituted or further substituted with 1, 2 or 3 substituents selected from the group consisting of alkyl, —CN, halogen, haloalkyl, —OR a , —N(R b ) 2 , and —N(R b )C(O)O(R b ), wherein R a is alkyl and R b at each occurrence, is independently hydrogen or alkyl;

L 1 is —(CH 2 ) p —;

p is 1, 2, or 3;

L 2 is —N(R 5 )—(CH 2 ) q —, —N(R 5 )—CH(R 6 )—, (i), (ii), or (x);

R 5 is alkyl;

q is 1 or 2;

Y is a bond, CR 2 R 3 , or CH 2 CR 2 R 3 ;

R 2 is hydrogen or phenyl;

R 3 is hydrogen; or

R 4 and R 5 taken together are —(CH 2 ) s —;

s is 1; or

R 4 and R 6 taken together are CH 2 .

7. The compound according to claim 1 , wherein

n is 2;

X is CH 2 ;

Ar 1 is phenyl; and

R 1 is hydrogen, alkyl, or G 1 , wherein G 1 is phenyl;

wherein the phenyl groups of Ar 1 and R 1 are independently either unsubstituted or further substituted with 1, 2, or 3 substituents selected from the group consisting of halogen and —OR a , wherein R a is alkyl.

8. The compound according to claim 7 , wherein

Ar 2 is phenyl either unsubstituted or further substituted with 1, 2, or 3 substituents selected from the group consisting of halogen and —OR a , wherein R a is alkyl;

L 1 is —CH 2 C(O)—;

L 2 is —N(R 5 )— or —N(R 5 )—(CH 2 ) q —;

q is 1;

Y is CR 2 R 3 ;

R 2 is hydrogen; and

R 3 is hydrogen; or

R 2 and R 3 taken together with the carbon atom to which they are attached form a cycloalkyl.

9. The compound according to claim 7 , wherein

Ar 2 is phenyl, wherein phenyl is either unsubstituted or further substituted with 1, 2 or 3 substituents selected from the group consisting of halogen and —OR a , wherein R a is alkyl;

L 1 is —(CH 2 ) p —;

p is 2 or 3;

L 2 is —N(R 5 )—, or —N(R 5 )—(CH 2 ) q —;

q is 1 or 3;

Y is O or CR 2 R 3 ; and

R 2 and R 3 are each hydrogen.

10. The compound according to claim 7 , wherein

Ar 2 is phenyl or heteroaryl, wherein phenyl and heteroaryl are either unsubstituted or further substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl, —CN, halogen, haloalkyl, and —OR a , wherein R a is alkyl;

L 1 is —CH 2 C(O)—;

L 2 is —N(R 5 )—, —N(R 5 )—(CH 2 ) q —, —NH—CH(R 5 )—(CH 2 ) q —, (i), (ii), (iii), (iv), (v), (vi), or (viii);

R 5 is hydrogen, alkyl, or G 1 ;

q is 1, 2, or 3;

Y is a bond, CR 2 R 3 , O, N—O—CR 2 R 3 , C(O)OCR 2 R 3 , or S(O) 2 ;

R 2 is hydrogen or phenyl, wherein the phenyl is either unsubstituted or further substituted with 1, 2, or 3 halogen substituents; and

R 3 is hydrogen, alkyl, or hydroxyl; or

R 3 and R 5 taken together are —(CH 2 ) p — or —OCH 2 CH 2 —; wherein

p is 1, 2, 3 or 4; or

R 4 and R 5 taken together are a bond or —(CH 2 ) s —; wherein

s is 1.

11. The compound according to claim 7 , wherein

Ar 2 is indazolyl, pyridinyl, pyrimidinyl or phenyl, wherein phenyl is either unsubstituted or further substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, haloalkyl, or —OR a , wherein R a is hydrogen, alkyl, or haloalkyl;

L 1 is —(CH 2 ) p —;

p is 1, 2, or 3;

L 2 is —N(R 5 )—CH(R 6 )—, (i), or (x);

R 5 is alkyl;

Y is a bond, CR 2 R 3 , CH 2 CR 2 R 3 , or CR 2 R 3 O;

R 2 is hydrogen; and

R 3 is hydrogen; or

R 4 and R 6 taken together are CH 2 .

12. The compound according to claim 7 , wherein

Ar 2 is phenyl either unsubstituted or further substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl, halogen, or haloalkyl; and

L 1 -L 2 Y taken together are S(O) r .

13. The compound according to claim 1 , wherein

Ar 1 and R 1 are phenyl optionally substituted with fluorine;

Ar 2 is phenyl optionally substituted with haloalkyl;

X is CH 2 ;

L 1 is —CH 2 C(O)—;

L 2 is (i);

Y is CR 2 R 3 ;

R 2 is hydrogen or phenyl; and

R 3 is hydrogen.

14. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

1-[2-(4-benzhydrylpiperazin-1-yl)-2-oxoethyl]-3,3-diphenylpyrrolidin-2-one;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-{[6-(trifluoromethyl)pyridin-3-yl]methyl}acetamide;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-(1,3-thiazol-2-ylmethyl)acetamide;

N-[(1-methyl-1H-pyrazol-3-yl)methyl]-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

N-(5-chloropyridin-2-yl)-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

N-benzyl-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-[3-(trifluoromethyl)benzyl]acetamide;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-[4-(trifluoromethyl)benzyl]acetamide;

N-[cyclopropyl(phenyl)methyl]-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-{2-[3-(trifluoromethyl)phenyl]ethyl}acetamide;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-(1-phenylcyclobutyl)acetamide;

N-(4-fluorobenzyl)-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

N-(3,3-diphenylpropyl)-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

N-benzhydryl-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

N-(2,2-diphenylethyl)-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

N-(2,2-diphenylpropyl)-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

1-[2-(3,3-diphenylpyrrolidin-1-yl)-2-oxoethyl]-3,3-diphenylpyrrolidin-2-one;

1-[2-(3-benzylpiperazin-1-yl)-2-oxoethyl]-3,3-diphenylpyrrolidin-2-one;

1-[2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-3,3-diphenylpyrrolidin-2-one;

1-{2-oxo-2-[5-(trifluoromethyl)-1,3-dihydro-2H-isoindol-2-yl]ethyl}-3,3-diphenylpyrrolidin-2-one;

1-[2-oxo-2-(3-phenylpyrrolidin-1-yl)ethyl]-3,3-diphenylpyrrolidin-2-one;

N-2,3-dihydro-1H-inden-2-yl-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

1-[2-(2,2-diphenylmorpholin-4-yl)-2-oxoethyl]-3,3-diphenylpyrrolidin-2-one;

1-[2-(3,3-diphenylpiperidin-1-yl)-2-oxoethyl]-3,3-diphenylpyrrolidin-2-one;

1-[2-(4,4-diphenylpiperidin-1-yl)-2-oxoethyl]-3,3-diphenylpyrrolidin-2-one;

1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3,3-diphenylpyrrolidin-2-one;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-1,2,3,4-tetrahydronaphthalen-1-ylacetamide;

4-[(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetyl]-1-[3-(trifluoromethyl)benzyl]piperazin-2-one;

1-benzhydryl-4-[(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetyl]piperazin-2-one;

1-[2-(4-benzhydrylpiperidin-1-yl)-2-oxoethyl]-3,3-diphenylpyrrolidin-2-one;

1-{2-[4-(diphenylmethylene)piperidin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

1-(2-{4-[bis(4-fluorophenyl)(hydroxy)methyl]piperidin-1-yl}-2-oxoethyl)-3,3-diphenylpyrrolidin-2-one;

1-{2-[4-(hydroxy {bis[3-(trifluoromethyl)phenyl]}methyl)piperidin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

1-(2-{4-[hydroxy(diphenyl)methyl]piperidin-1-yl}-2-oxoethyl)-3,3-diphenylpyrrolidin-2-one;

1-{2-[4-(5-methoxy-1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

1-{2-[4-(2,6-dichlorobenzyl)piperazin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

1-(2-oxo-2-{4-[3-(trifluoromethyl)benzyl]piperazin-1-yl}ethyl)-3,3-diphenylpyrrolidin-2-one;

1-{2-[4-(4-fluorobenzyl)piperazin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

N-[(1-benzylpyrrolidin-3-yl)methyl]-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

N-(1-benzyl-3-methylpyrrolidin-3-yl)-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-{1-[3-(trifluoromethyl)benzyl]piperidin-4-yl}acetamide;

1-[2-oxo-2-(4-{[3-(trifluoromethyl)benzyl]amino}piperidin-1-yl)ethyl]-3,3-diphenylpyrrolidin-2-one;

1-{2-[4-(2,4-dichlorobenzyl)piperazin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

1-[2-oxo-2-(4-{1-[3-(trifluoromethyl)phenyl]ethyl}piperazin-1-yl)ethyl]-3,3-diphenylpyrrolidin-2-one;

1-(2-{4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}-2-oxoethyl)-3,3-diphenylpyrrolidin-2-one;

1-(2-{4-[(4-fluorophenyl)(phenyl)methyl]piperazin-1-yl}-2-oxoethyl)-3,3-diphenylpyrrolidin-2-one;

1-(2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}-2-oxoethyl)-3,3-diphenylpyrrolidin-2-one;

N-(1-benzhydrylpiperidin-4-yl)-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

1-{2-[(2R)-4-benzhydryl-2-methylpiperazin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

1-{2-[(4aS,7aS)-6-benzhydryloctahydro-1H-pyrrolo[3,4-b]pyridin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

1-{2-[(4aR,7aR)-6-benzhydryloctahydro-1H-pyrrolo[3,4-b]pyridin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

1-(2-{4-[(2,2-diphenylethyl)amino]piperidin-1-yl}-2-oxoethyl)-3,3-diphenylpyrrolidin-2-one;

1-{2-[4-(5-chloropyridin-2-yl)piperazin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

1-{2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

1-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]ethyl}-3,3-diphenylpyrrolidin-2-one;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-{(3aS*,4S*,6aR*)-2-[3-(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-4-yl}acetamide;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-{(3aS*,4R*,6aR*)-2-[3-(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-4-yl}acetamide;

1-[2-(4-benzhydrylpiperazin-1-yl)-2-oxoethyl]-3,3-bis(4-fluorophenyl)pyrrolidin-2-one;

2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-(2,2-diphenylpropyl)acetamide;

3,3-bis(4-fluorophenyl)-1-(2-oxo-2-{4-[3-(trifluoromethyl)benzyl]piperazin-1-yl}ethyl)pyrrolidin-2-one;

1-[2-(3,3-diphenylpyrrolidin-1-yl)-2-oxoethyl]-3,3-bis(4-fluorophenyl)pyrrolidin-2-one;

3,3-diphenyl-1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one;

1-{2-[4-(3,5-dimethoxybenzyl)piperazin-1-yl]ethyl}-3,3-bis(4-fluorophenyl)pyrrolidin-2-one;

4-benzhydryl-1-[2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)ethyl]piperazin-2-one;

3,3-dimethyl-1-[2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)ethyl]-4-(thien-2-ylmethyl)piperazin-2-one;

1-benzhydryl-4-[2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)ethyl]piperazin-2-one;

3,3-diphenyl-1-{2-[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]ethyl}pyrrolidin-2-one;

1-[2-(4-benzhydrylpiperazin-1-yl)-2-oxoethyl]-3,3-diphenylpiperidin-2-one;

1-[2-(2,2-diphenylmorpholin-4-yl)-2-oxoethyl]-3,3-diphenylpiperidin-2-one;

1-[2-oxo-2-(2-phenylmorpholin-4-yl)ethyl]-3,3-diphenylpiperidin-2-one;

1-[2-(3,3-diphenylpiperidin-1-yl)-2-oxoethyl]-3,3-diphenylpiperidin-2-one;

1-[2-(4,4-diphenylpiperidin-1-yl)-2-oxoethyl]-3,3-diphenylpiperidin-2-one;

1-{2-[2-(4-fluorophenyl)pyrrolidin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

1-{2-[2-(4-fluorophenyl)piperidin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

N-(6-fluoro-3,4-dihydro-2H-chromen-4-yl)-2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamide;

1-[2-(4-benzhydrylpiperidin-1-yl)-2-oxoethyl]-3,3-diphenylpiperidin-2-one;

N-(2,2-diphenylpropyl)-2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamide;

1-(2-{4-[hydroxy(diphenyl)methyl]piperidin-1-yl}-2-oxoethyl)-3,3-diphenylpiperidin-2-one;

1-(2-oxo-2-{4-[3-(trifluoromethyl)benzyl]piperazin-1-yl}ethyl)-3,3-diphenylpiperidin-2-one;

1-(2-oxo-2-{4-[4-(trifluoromethyl)benzyl]piperazin-1-yl}ethyl)-3,3-diphenylpiperidin-2-one;

1-{2-[4-(3-chlorobenzyl)piperazin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

1-(2-{4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}-2-oxoethyl)-3,3-diphenylpiperidin-2-one;

1-benzhydryl-4-[(2-oxo-3,3-diphenylpiperidin-1-yl)acetyl]piperazin-2-one;

1-[2-oxo-2-(4-{[3-(trifluoromethyl)phenyl]sulfonyl}piperazin-1-yl)ethyl]-3,3-diphenylpiperidin-2-one;

N-(1-benzhydrylpiperidin-4-yl)-2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamide;

N-(1-benzhydryl-3-methylpyrrolidin-3-yl)-2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamide;

1-{2-[4-(benzhydrylamino)piperidin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

1-{2-[(4aS,7aS)-1-benzhydryloctahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

N-(1-benzyl-3-methylpyrrolidin-3-yl)-2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamide;

1-[2-(4-benzhydrylpiperazin-1-yl)-2-oxoethyl]-3,3-bis(4-fluorophenyl)piperidin-2-one;

1-[2-(4-benzhydrylpiperazin-1-yl)-2-oxoethyl]-3-phenylpiperidin-2-one;

1-(2-{4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}-2-oxoethyl)-3-phenylpiperidin-2-one;

1-(2-oxo-2-{4-[3-(trifluoromethyl)benzyl]piperazin-1-yl}ethyl)-3-phenylpiperidin-2-one;

1-{2-[4-(2,4-dichlorobenzyl)piperazin-1-yl]-2-oxoethyl}-3-phenylpiperidin-2-one;

1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3-phenylpiperidin-2-one;

1-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]ethyl}-3-phenylpiperidin-2-one;

N-[1-(4-fluorophenyl)cyclobutyl]-2-(2-oxo-3-phenylpiperidin-1-yl)acetamide;

1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3-methyl-3-phenylpiperidin-2-one;

3,3-diphenyl-1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-2-one;

1-{[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpiperidin-2-one;

1-{2-[[3-(3,5-dimethoxyphenoxy)propyl](methyl)amino]ethyl}-3,3-bis(4-fluorophenyl)pyrrolidin-2-one;

1-{2-[[2-hydroxy-3-(quinolin-5-yloxy)propyl] (methyl)amino]ethyl}-3,3-bis(4-methoxyphenyl)pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-{2-[[2-hydroxy-3-(2-{(E)-2-[3-(methoxymethyl)isoxazol-5-yl]vinyl}phenoxy)propyl](methyl)amino]ethyl}pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-{2-[[2-hydroxy-3-(quinolin-5-yloxy)propyl](methyl)amino]ethyl}pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-{2-[4-(3,4,5-trimethoxybenzyl)piperazin-1-yl]ethyl}pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-{3-[4-(3,4,5-trimethoxybenzyl)piperazin-1-yl]propyl}pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)pyrrolidin-2-one;

N-{2-[3,3-bis(4-methoxyphenyl)-2-oxopyrrolidin-1-yl]ethyl}benzamide;

1-{2-[2,3-dihydro-1H-inden-2-ylmethyl)amino]ethyl}-3,3-bis(4-methoxyphenyl)piperidin-2-one;

1-{3-[2,3-dihydro-1H-inden-2-yl(methyl)amino]propyl}-3,3-bis(4-fluorophenyl)pyrrolidin-2-one;

1-{2-[[3-(3,5-dimethoxyphenoxy)propyl](methyl)amino]ethyl}-3,3-bis(4-methoxyphenyl)piperidin-2-one;

1-{3-[[3-(3,5-dimethoxyphenoxy)propyl](methyl)amino]propyl}-3,3-bis(4-methoxyphenyl)piperidin-2-one;

1-{3-[methyl(2-phenylethyl)amino]propyl}-3,3-diphenylpiperidin-2-one;

1-{2-[[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino]ethyl}-3,3-diphenylpiperidin-2-one;

1-{3-[[2-(3,5-dimethoxyphenyl)ethyl](methyl)amino]propyl}-3,3-bis(4-methoxyphenyl)piperidin-2-one;

3,3-bis(4-fluorophenyl)-1-{2-[[2-(3-methoxyphenyl)ethyl](methyl)amino]ethyl}piperidin-2-one;

3,3-bis(4-fluorophenyl)-1-{3-[[2-(3-methoxyphenyl)ethyl](methyl)amino]propyl}piperidin-2-one;

3,3-bis(4-fluorophenyl)-1-{2-[methyl(2-phenylethyl)amino]ethyl}piperidin-2-one;

3,3-bis(4-fluorophenyl)-1-{3-[methyl(2-phenylethyl)amino]propyl}piperidin-2-one;

3,3-bis(4-methoxyphenyl)-1-{2-[[2-(3-methoxyphenyl)ethyl](methyl)amino]ethyl}piperidin-2-one;

3,3-bis(4-methoxyphenyl)-1-{3-[[2-(3-methoxyphenyl)ethyl](methyl)amino]propyl}piperidin-2-one;

1-{2-[[2-(2,4-dimethoxyphenyl)ethyl](methyl)amino]ethyl}-3,3-bis(4-methoxyphenyl)piperidin-2-one;

1-{3-[(3,5-dimethoxybenzyl)(methyl)amino]propyl}-3,3-bis(4-methoxyphenyl)piperidin-2-one;

3-isopropyl-3-(3-methoxyphenyl)-1-{3-[[2-(3-methoxyphenyl)ethyl](methyl)amino]propyl}piperidin-2-one;

1-{3-[[2-(4-fluorophenyl)ethyl](methyl)amino]propyl}-3-isopropyl-3-(3-methoxyphenyl)piperidin-2-one;

3-isopropyl-3-(3-methoxyphenyl)-1-{2-[[2-(4-methoxyphenyl)ethyl](methyl)amino]ethyl}piperidin-2-one;

1-{3-[4-(3,5-dimethoxybenzyl)piperazin-1-yl]propyl}-3,3-bis(4-methoxyphenyl)piperidin-2-one;

1-{2-[4-(3,5-dimethoxybenzyl)piperazin-1-yl]ethyl}-3,3-bis(4-methoxyphenyl)piperidin-2-one;

1-{3-[4-(3,5-dimethoxybenzyl)piperazin-1-yl]propyl}-3-isopropyl-3-(3-methoxyphenyl)piperidin-2-one;

3,3-diphenyl-1-[2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]piperidin-2-one;

3,3-bis(4-fluorophenyl)-1-[3-(4-pyrimidin-2-ylpiperazin-1-yl)propyl]piperidin-2-one;

3,3-bis(4-fluorophenyl)-1-[2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]piperidin-2-one;

3,3-bis(4-fluorophenyl)-1-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}piperidin-2-one;

3,3-bis(4-fluorophenyl)-1-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl}piperidin-2-one;

3,3-bis(4-fluorophenyl)-1-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)piperidin-2-one;

3,3-diphenyl-1-(3-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}propyl)piperidin-2-one;

3,3-diphenyl-1-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)piperidin-2-one;

3,3-bis(4-fluorophenyl)-1-(3-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}propyl)piperidin-2-one;

N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methyl-2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamide;

3,3-diphenyl-1-{[3-(trifluoromethyl)phenyl]sulfonyl}pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-{[3-(trifluoromethyl)phenyl]sulfonyl}pyrrolidin-2-one;

3,3-diphenyl-1-{[3-(trifluoromethyl)phenyl]sulfonyl}piperidin-2-one;

1-[(3-{[(cis-2,6-dimethylmorpholin-4-yl]carbonyl}phenyl)sulfonyl]-3,3-diphenylpyrrolidin-2-one;

3,3-diphenyl-1-{[2-(trifluoromethyl)phenyl]sulfonyl}pyrrolidin-2-one;

3,3-diphenyl-1-{[4-(trifluoromethyl)phenyl]sulfonyl}pyrrolidin-2-one;

N-cyclopropyl-3-[(2-oxo-3,3-diphenylpyrrolidin-1-yl)sulfonyl]benzamide;

1-{[2-chloro-4-(trifluoromethyl)phenyl]sulfonyl}-3,3-diphenylpyrrolidin-2-one;

1-[2-(7-benzyl-2,7-diazaspiro[3.5]non-2-yl)-2-oxoethyl]-3,3-bis(4-fluorophenyl)pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-(2-oxo-2-{7-[4-(trifluoromethyl)benzyl]-2,7-diazaspiro[3.5]non-2-yl}ethyl)pyrrolidin-2-one;

1-{[3-(1H-indazol-5-yl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpiperidin-2-one;

3,3-diphenyl-1-(3-{3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}propyl)pyrrolidin-2-one;

1-({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)-3,3-diphenylpyrrolidin-2-one;

1-({4-methyl-2-[3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)-3,3-diphenylpyrrolidin-2-one;

1-{2-[4-(4-chlorophenoxy)piperidin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

1-{2-[4-(3-chlorophenoxy)piperidin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

1-{2-[4-(3,4-difluorophenoxy)piperidin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

1-{2-[4-(4-methoxyphenoxy)piperidin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

1-(2-oxo-2-{4-[3-(trifluoromethyl)phenoxy]piperidin-1-yl}ethyl)-3,3-diphenylpiperidin-2-one;

1-(2-{4-[(benzyloxy)imino]piperidin-1-yl}-2-oxoethyl)-3,3-diphenylpiperidin-2-one;

1-(2-oxo-2-{4-[5-(trifluoromethyl)-1H-1,2,3-benzotriazol-1-yl]piperidin-1-yl}ethyl)-3,3-diphenylpiperidin-2-one;

1-({3-[2-(4-chlorophenyl)ethyl]-1,2,4-oxadiazol-5-yl}methyl)-3,3-bis(4-fluorophenyl)pyrrolidin-2-one;

2-(2-oxo-3,3-diphenylpiperidin-1-yl)-N-piperidin-4-yl-N-[4-(trifluoromethyl)phenyl]acetamide;

1-{2-[3-(3,4-dimethoxybenzyl)-3-methylpiperazin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

N-(1,3-oxazol-2-ylmethyl)-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

1-{2-[4-(2,4-dichlorobenzyl)piperazin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

1-{[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpiperidin-2-one;

1-(2-{4-[bis(4-fluorophenyl)methylene]piperidin-1-yl}-2-oxoethyl)-3,3-diphenylpiperidin-2-one;

1-[2-(3,3-diphenylpyrrolidin-1-yl)-2-oxoethyl]-3,3-bis(4-fluorophenyl)piperidin-2-one;

1-[2-(4,4-diphenylpiperidin-1-yl)-2-oxoethyl]-3,3-bis(4-fluorophenyl)piperidin-2-one;

1-[2-(3,3-diphenylpyrrolidin-1-yl)-2-oxoethyl]-3,3-diphenylpiperidin-2-one;

3,3-bis(4-fluorophenyl)-1-(2-oxo-2-{4-[3-(trifluoromethyl)benzyl]piperazin-1-yl}ethyl)piperidin-2-one;

N-(1-benzhydrylazetidin-3-yl)-2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamide;

3,3-diphenyl-1-({3-[6-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-2-one;

1-{2-oxo-2-[5-(trifluoromethyl)-1,3-dihydro-2H-isoindol-2-yl]ethyl}-3-phenylpiperidin-2-one;

3,3-diphenyl-1-({3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-2-one;

2-(2-oxo-3,3-diphenylpiperidin-1-yl)-N-{1-[3-(trifluoromethyl)benzyl]azetidin-3-yl}acetamide;

3-phenyl-1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-2-one;

benzyl 4-[(2-oxo-3,3-diphenylpiperidin-1-yl)acetyl]piperazine-1-carboxylate;

N-{1-[4-fluoro-3-(trifluoromethyl)benzyl]piperidin-4-yl}-2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamide;

1-(2-{4-[4-fluoro-3-(trifluoromethyl)benzyl]piperazin-1-yl}-2-oxoethyl)-3,3-diphenylpiperidin-2-one;

2-(2-oxo-3,3-diphenylpiperidin-1-yl)-N-{(3S)-1-[3-(trifluoromethyl)benzyl]pyrrolidin-3-yl}acetamide;

2-(2-oxo-3,3-diphenylpiperidin-1-yl)-N-{(3R)-1-[3-(trifluoromethyl)benzyl]pyrrolidin-3-yl}acetamide;

(3S)-1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3-phenylpiperidin-2-one;

(3R)-1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3-phenylpiperidin-2-one;

3-(4-fluorophenyl)-1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-2-one;

N-(5-chloropyridin-2-yl)-2-(2-oxo-3-phenylpiperidin-1-yl)acetamide;

1-{[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpyrrolidin-2-one;

1-{[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpyrrolidin-2-one;

1-{[3-(4-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpyrrolidin-2-one;

3,3-diphenyl-1-({5-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}methyl)pyrrolidin-2-one;

N-methyl-2-(2-oxo-3,3-diphenylpiperidin-1-yl)-N-{1-[3-(trifluoromethyl)benzyl]piperidin-4-yl}acetamide;

N-{1-[4-fluoro-3-(trifluoromethyl)benzyl]azetidin-3-yl}-2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamide;

3,3-diphenyl-1-({3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-2-one;

2-(2-oxo-3,3-diphenylpiperidin-1-yl)-N-{1-[3-(trifluoromethyl)benzyl]piperidin-4-yl}acetamide;

N-{1-[2-fluoro-3-(trifluoromethyl)benzyl]azetidin-3-yl}-2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamide;

1-{[3-(4-tert-butylphenyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpyrrolidin-2-one;

1-{2-[3,3-bis(4-fluorophenyl)pyrrolidin-1-yl]-2-oxoethyl}-3,3-diphenylpyrrolidin-2-one;

1-{2-[3,3-bis(4-fluorophenyl)pyrrolidin-1-yl]-2-oxoethyl}-3,3-bis(4-fluorophenyl)pyrrolidin-2-one;

1-{2-[3,3-bis(4-fluorophenyl)pyrrolidin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

1-{[3-(4-hydroxyphenyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpiperidin-2-one;

1-{[3-(4-chlorobenzyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpiperidin-2-one;

2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-{1-[3-(trifluoromethyl)benzyl]piperidin-4-yl}acetamide;

1-{[3-(4-isobutoxyphenyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpiperidin-2-one;

3,3-bis(4-fluorophenyl)-1-(2-oxo-2-{(4aS,7aS)-1-[3-(trifluoromethyl)benzyl]octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl}ethyl)pyrrolidin-2-one;

3,3-diphenyl-1-({3-[6-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-({3-[6-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one;

1-({3-[2-(4-chlorophenyl)ethyl]-1,2,4-oxadiazol-5-yl}methyl)-3,3-diphenylpiperidin-2-one;

1-{[3-(6-chloropyridin-3-yl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpyrrolidin-2-one;

1-{[3-(3,5-difluorophenyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpyrrolidin-2-one;

3-(4-fluorophenyl)-1-{2-oxo-2-[5-(trifluoromethyl)-1,3-dihydro-2H-isoindol-2-yl]ethyl}pyrrolidin-2-one;

2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]acetamide;

2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-[4-(trifluoromethyl)phenyl]acetamide;

3,3-diphenyl-1-({3-[5-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one;

3,3-diphenyl-1-({3-[4-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one;

3,3-diphenyl-1-[(3-pyridin-3-yl-1,2,4-oxadiazol-5-yl)methyl]pyrrolidin-2-one;

3,3-diphenyl-1-[(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)methyl]pyrrolidin-2-one;

1-{4-oxo-4-[5-(trifluoromethyl)-1,3-dihydro-2H-isoindol-2-yl]butyl}-3,3-diphenylpyrrolidin-2-one;

2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]acetamide;

2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-(5-chloropyridin-2-yl)acetamide;

2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-[6-(trifluoromethyl)pyridin-2-yl]acetamide;

1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3-(4-fluorophenyl)pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-{2-oxo-2-[5-(trifluoromethyl)-1,3-dihydro-2H-isoindol-2-yl]ethyl}pyrrolidin-2-one;

2-[3-(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]acetamide;

3,3-diphenyl-1-[(3-pyrazin-2-yl-1,2,4-oxadiazol-5-yl)methyl]pyrrolidin-2-one;

tert-butyl 5-{5-[(2-oxo-3,3-diphenylpyrrolidin-1-yl)methyl]-1,2,4-oxadiazol-3-yl}pyridin-2-ylcarbamate;

3,3-bis(4-fluorophenyl)-1-[(3-pyrazin-2-yl-1,2,4-oxadiazol-5-yl)methyl]pyrrolidin-2-one;

1-{[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-bis(4-fluorophenyl)pyrrolidin-2-one;

1-{[3-(6-aminopyridin-3-yl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpyrrolidin-2-one;

4-(5-{[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]methyl}-1,2,4-oxadiazol-3-yl)benzonitrile;

(3S)-3-(4-fluorophenyl)-1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one;

(3R)-3-(4-fluorophenyl)-1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one;

3-(4-fluorophenyl)-1-({3-[6-(trifluoromethyl)pyridin-3-yl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one;

2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-{1-[3-fluoro-4-(trifluoromethyl)benzyl]azetidin-3-yl}acetamide;

1-(2-oxo-2-{3-[4-(trifluoromethyl)phenyl]azetidin-1-yl}ethyl)-3,3-diphenylpiperidin-2-one;

4-{1-[(2-oxo-3,3-diphenylpiperidin-1-yl)acetyl]azetidin-3-yl}benzonitrile;

N-(1-benzylazetidin-3-yl)-2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]acetamide;

1-(2-oxo-2-{4-[3-(trifluoromethyl)phenyl]piperidin-1-yl}ethyl)-3,3-diphenylpiperidin-2-one;

1-{2-[4-(4-fluorophenyl)piperidin-1-yl]-2-oxoethyl}-3,3-diphenylpiperidin-2-one;

1-(2-oxo-2-{4-[4-(trifluoromethyl)phenyl]piperidin-1-yl}ethyl)-3,3-diphenylpiperidin-2-one;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-[5-(trifluoromethyl)pyridin-2-yl]acetamide;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-[6-(trifluoromethyl)pyridin-2-yl]acetamide;

2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)-N-[6-(trifluoromethyl)pyridin-3-yl]acetamide;

N-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

1-(2-{4-[4-chloro-3-(trifluoromethyl)phenyl]-4-hydroxypiperidin-1-yl}-2-oxoethyl)-3,3-diphenylpiperidin-2-one;

N-(5-cyanopyridin-2-yl)-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetamide;

2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-(5-cyanopyridin-2-yl)acetamide;

1-[2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-3-(4-fluorophenyl)pyrrolidin-2-one;

3-(4-fluorophenyl)-1-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]ethyl}pyrrolidin-2-one;

1-[2-(7-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-3-(4-fluorophenyl)pyrrolidin-2-one;

1-[2-(7-chloro-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-3-(4-fluorophenyl)pyrrolidin-2-one;

1-[2-(6-chloro-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-3-(4-fluorophenyl)pyrrolidin-2-one;

1-[2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-3,3-bis(4-fluorophenyl)pyrrolidin-2-one;

3,3-bis(4-fluorophenyl)-1-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]ethyl}pyrrolidin-2-one;

1-[2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-3,3-diphenylpiperidin-2-one;

1-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]ethyl}-3,3-diphenylpiperidin-2-one;

1-({3-[2-(2-chlorophenyl)ethyl]-1,2,4-oxadiazol-5-yl}methyl)-3,3-diphenylpiperidin-2-one;

1-({3-[(4-chlorophenoxy)methyl]-1,2,4-oxadiazol-5-yl}methyl)-3,3-diphenylpiperidin-2-one;

(+)-3-(4-fluorophenyl)-1-{2-oxo-2-[5-(trifluoromethyl)-1,3-dihydro-2H-isoindol-2-yl]ethyl}pyrrolidin-2-one;

(−)-3-(4-fluorophenyl)-1-{2-oxo-2-[5-(trifluoromethyl)-1,3-dihydro-2H-isoindol-2-yl]ethyl}pyrrolidin-2-one;

1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3-[4-(trifluoromethyl)phenyl]pyrrolidin-2-one;

1-{2-oxo-2-[5-(trifluoromethyl)-1,3-dihydro-2H-isoindol-2-yl]ethyl}-3-[4-(trifluoromethyl)phenyl]pyrrolidin-2-one;

3-(2-chloro-4-fluorophenyl)-1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]pyrrolidin-2-one;

3-(2-chloro-4-fluorophenyl)-1-{2-oxo-2-[5-(trifluoromethyl)-1,3-dihydro-2H-isoindol-2-yl]ethyl}pyrrolidin-2-one;

3-(3,4-dichlorophenyl)-1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]pyrrolidin-2-one;

1-(2-{4-[bis(4-fluorophenyl)(hydroxy)methyl]piperidin-1-yl}-2-oxoethyl)-3,3-bis(4-fluorophenyl)pyrrolidin-2-one; and

1-(2-{4-[bis(4-fluorophenyl)(hydroxy)methyl]piperidin-1-yl}-2-oxoethyl)-3,3-diphenylpiperidin-2-one.

15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.

16. A method of treating pain in a subject in need thereof, comprising: administering to the subject a therapeutically suitable amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the pain is acute pain, chronic pain, neuropathic pain, inflammatory pain, visceral pain, cancer pain, allodynia, fibromyalgia, sciatica, back pain, and headache pain including migraine, or combinations thereof.

17. The compound according to claim 2 , wherein

Ar 2 is phenyl either unsubstituted or further substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl, halogen, haloalkyl, —C(O)R b , —C(O)N(R b ) 2 , wherein R b at each occurrence, is independently hydrogen, alkyl, or G 1 ; and

L 1 -L 2 Y taken together are S(O) r .

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 2, 2014
From: ABBOTT GMBH & CO KG
To: ABBVIE DEUTSCHLAND GMBH & CO KG
Reel/Frame 032578/0827 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 17, 2013
From: ABBOTT LABORATORIES
To: ABBVIE INC.
Reel/Frame 030237/0597 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 29, 2009
From: BHATIA, PRAMILA A.; DOHERTY, GEORGE A.; DRIZIN, IRENE; PERNER, RICHARD J.; STEWART, ANDREW O.; ZHANG, QINGWEI
To: ABBOTT LABORATORIES
Reel/Frame 023711/0261 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 29, 2009
From: MACK, HELMUT
To: ABBOTT GMBH & CO. KG
Reel/Frame 023711/0270 →