Compounds as calcium channel blockers
View Patent ↗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.
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 .