IP Library › Granted Patent US 8,691,865
Granted Patent B2
US 8,691,865 · App. 13/114,829 · Granted Apr 8, 2014

Substituted octahydrocyclopenta[C]pyrrol-4-amines as calcium channel blockers

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Quick Facts
Patent No.
US 8,691,865
App. No.
13/114,829
Granted
Apr 8, 2014
Kind
B2
Abstract

The present application relates to calcium channel inhibitors containing compounds of formula (I) wherein L 1 , L 2 , R 1 , R 2 , and R 3 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 (373)

1. A compound of formula (I),

or a pharmaceutically acceptable salt thereof, wherein

L 1 -R 1 taken together are G 1 ;

L 2 is —(CR c R d ) p —, C(O), C(O)N(R 4 ), S(O) 2 , SO 2 N(R 5 ), or C(O)O;

R 2 is alkyl, haloalkyl, hydroxyalkyl, G 2 , -G 2 -G 3 , —C(R c )(G 2 )(G 3 ), —CH(OH)CF 3 , —(CR c R d ) p —CH(OH)CF 3 , —(CR c R d ) p -G 2 , —(CR c R d ) p —CH(G 2 )(G 3 ), —(CR g R h ) q —N(R 5 )—C(O)O(alkyl), —(CR g R h ) q —N(R 5 )—C(O)O-G 2 , —(CR g R h ) q —N(R 5 )—C(O)(alkyl), —(CR g R h ) q —N(R 5 )—SO 2 R 6 , —(CR g R h ) q —N(R 4 )(R 5 ), —(CR g R h ) q —N(R 5 )—C(O)N(R 5 )-(alkyl), —(CR g R h ) q —N(R 5 )—C(O)N(R 5 )-G 2 , or —C(O)N(R 4 )(R 5 ); or

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

q, at each occurrence, is 1, 2, 3, 4, or 5;

R c and R d , at each occurrence, are each independently hydrogen, alkyl, arylalkyl, halogen, haloalkyl or OR 7 ; or

R c and R d , together with the carbon atom to which they are attached, optionally form a C 3-6 cycloalkyl ring;

R g and R h , at each occurrence, are each independently hydrogen, alkyl, halogen, haloalkyl, hydroxyalkyl, OR 7 , cycloalkylalkyl, heteroaryl, arylalkyl, or heteroarylalkyl; wherein the aryl, cycloalkyl and heteroaryl groups of aryl, cycloalkyl and heteroaryl are each independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of alkyl and haloalkyl;

G 1 is monocyclic aryl or monocyclic heteroaryl; wherein G 1 is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, haloalkyl, halogen, nitro, oxo, phenyl, N(R 7 ) 2 , N(R 7 )C(O)R 7 , OR 7 , C(O)R 7 , C(O)OR 7 , C(O)N(R 7 ) 2 , SR 7 , SO 2 R 8 , and SO 2 N(R 7 ) 2 ;

G 2 and G 3 at each occurrence, are each independently aryl, cycloalkyl, cycloalkenyl, heteroaryl, or heterocycle; wherein G 2 and G 3 at each occurrence are each independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, haloalkyl, halogen, nitro, oxo, phenyl, N(R 7 ) 2 , N(R 7 )C(O)R 7 , OR 7 , C(O)R 7 , C(O)OR 7 , C(O)N(R 7 ) 2 , SR 7 , SO 2 R 8 , and SO 2 N(R 7 ) 2 ;

R 3 is hydrogen, alkyl, haloalkyl, cycloalkyl, or cycloalkylalkyl;

R 4 , R 5 , and R 7 , at each occurrence, are each independently hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, or haloalkyl; wherein said aryl, the aryl of arylalkyl and cycloalkyl are independently unsubstituted or substituted with 1, 2 3, 4, or 5 substituents independently selected from the group consisting of alkyl, haloalkyl, and halogen; and

R 6 is alkyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, or heterocycle; wherein said aryl, heteroaryl, and heterocycle are independently unsubstituted or substituted with 1, 2 3, 4, or 5 substituents independently selected from the group consisting of alkyl, haloalkyl, and halogen;

R 8 is alkyl or haloalkyl.

2. The compound or salt according to claim 1 , wherein

G 1 is monocyclic aryl;

L 2 is C(O);

R 2 is —(CR c R d ) p -G 2 ; wherein G 2 is aryl;

p is 1;

R c and R d , together with the carbon atom to which they are attached form a C 3-6 cycloalkyl ring; and

R 3 is hydrogen.

3. The compound or salt according to claim 1 , wherein

L 2 is C(O);

R 2 is —(CR c R d ) p -G 2 ; wherein G 2 is aryl and p is 1 or 2;

R c and R d , at each occurrence are independently hydrogen, alkyl, or arylalkyl; and

R 3 is hydrogen or alkyl.

4. The compound or salt according to claim 1 , wherein

G 1 is monocyclic aryl;

L 2 is C(O)N(R 4 ), wherein R 4 is alkyl;

R 2 is G 2 , wherein G 2 is aryl; and

R 3 is hydrogen.

5. The compound or salt according to claim 1 , wherein

L 2 is C(O);

R 2 is —(CR c R d ) p -G 2 ; wherein

R c and R d at each occurrence are independently hydrogen, alkyl or OR 7 ;

p is 1;

G 2 is cycloalkyl or heterocycle; wherein said cycloalkyl or heterocycle is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of alkyl, haloalkyl, halogen, oxo and C(O)OR 7 ;

R 7 is hydrogen; and

R 3 is hydrogen.

6. The compound or salt according to claim 1 , wherein

G 1 is monocyclic aryl; and

R 3 is hydrogen or cycloalkyl.

7. The compound or salt according to claim 1 , wherein

G 1 is monocyclic aryl;

L 2 is C(O);

R 2 is —C(R c )(G 2 )(G 3 ), or —(CR c R d ) p —CH(G 2 )(G 3 ); wherein G 2 is aryl and G 3 is aryl or cycloalkyl;

R c and R d are each hydrogen; and

R 3 is hydrogen.

8. The compound or salt according to claim 1 , wherein

L 2 is C(O);

R 2 is —C(R c )(G 2 )(G 3 ); wherein G 2 and G 3 are each cycloalkyl;

R c hydrogen or OR 7 , wherein R 7 is hydrogen; and

R 3 is hydrogen.

9. The compound or salt according to claim 1 , wherein

G 1 is aryl;

L 2 is C(O);

R 2 is alkyl or G 2 , wherein G 2 is cycloalkyl or heterocycle; and

R 3 is hydrogen.

10. The compound or salt according to claim 1 , wherein

L 2 is C(O);

R 2 is —(CR g R h ) q —N(R 5 )—C(O)O(alkyl), —(CR g R h ) q —N(R 5 )—C(O)O-G 2 , —(CR g R h ) q —N(R 5 )—C(O)(alkyl), —(CR g R h ) q —N(R 5 )—SO 2 —R 6 , —(CR g R h ) q —N(R 4 )(R 5 ), —(CR g R h ) q —N(R 5 )—C(O)N(R 5 )-(alkyl), or —(CR g R h ) q —N(R 5 )—C(O)N(R 5 )-G 2 ;

q is 1 or 2;

R g and R h , at each occurrence, are each independently hydrogen, alkyl, arylalkyl, or cycloalkylalkyl;

R 4 and R 5 at each occurrence, are each independently hydrogen, alkyl, arylalkyl, cycloalkyl or cycloalkylalkyl;

R 6 is alkyl, aryl, or cycloalkyl;

G 2 is aryl or cycloalkyl; and

R 3 is hydrogen, alkyl, cycloalkyl or cycloalkylalkyl.

11. The compound or salt according to claim 1 , wherein

L 2 is S(O) 2 ;

R 2 is G 2 , wherein G 2 is aryl or heteroaryl; and

R 3 is hydrogen, alkyl or cycloalkyl.

12. The compound or salt according to claim 1 , wherein

L 2 is C(O);

R 2 is —(CR c R d ) p -G 2 ; wherein G 2 is aryl;

p is 1;

R c and R d , at each occurrence, are each independently hydrogen or alkyl; and

R 3 is hydrogen.

13. The compound or salt according to claim 1 , wherein

L 2 is —(CR c R d ) p —;

R c and R d are each independently hydrogen or alkyl;

p is 1;

R 2 is —C(O)N(R 4 )(R 5 ) or G 2 ;

R 4 and R 5 are each independently hydrogen or alkyl;

G 2 is aryl, cycloalkyl or heteroaryl; or

L 2 -R 2 taken together are hydrogen, alkyl, G 2 , or —C(R c )(G 2 )(G 3 ), wherein G 2 and G 3 are each aryl or heteroaryl and R c is hydrogen; and

R 3 is hydrogen or alkyl.

14. The compound or salt according to claim 1 , wherein

L 2 is C(O) or S(O) 2 ;

R 2 is G 2 or —C(R c )(G 2 )(G 3 ), wherein G 2 and G 3 are each aryl or heteroaryl and R c is hydrogen; and

R 3 is hydrogen, alkyl, or cycloalkyl.

15. The compound or salt according to claim 1 , wherein

R 5 at each occurrence is independently hydrogen, alkyl or cycloalkyl;

L 2 is C(O);

R 2 is —(CR g R h ) q N(R 4 )(R 5 ) or —(CR g R h ) q —N(R 5 )C(O)O(alkyl);

q is 1 or 2;

R 4 is hydrogen or alkyl;

R g and R h at each occurrence are each independently hydrogen or alkyl; and

R 3 is hydrogen.

16. The compound or salt of claim 1 , wherein

L 2 is C(O);

R 2 is haloalkyl, hydroxyalkyl, —CH(OH)CF 3 , —(CR c R d ) p —CH(OH)CF 3 , —(CR g R h ) q N(R 4 )(R 5 ) or —(CR g R h ) q —N(R 5 )C(O)O(alkyl);

p is 1 or 2;

q is 1 or 2;

R 4 is hydrogen, alkyl, or cycloalkylalkyl;

R 5 is hydrogen or alkyl;

R c and R d at each occurrence are each independently hydrogen or alkyl;

R g and R h at each occurrence are each independently hydrogen, alkyl, cycloalkylalkyl, or hydroxyalkyl; and

R 3 is hydrogen.

17. The compound or salt of claim 1 , wherein

L 2 is C(O) or S(O) 2 ;

R 2 is G 2 or G 2 -G 3 , wherein G 2 is aryl or heteroaryl and G 3 is aryl or heteroaryl; and

R 3 is hydrogen or alkyl.

18. The compound or salt of claim 1 , wherein

L 2 is —(CR c R d ) p —;

R c and R d , at each occurrence, are each independently hydrogen or alkyl;

p is 1, 2, or 3;

R 2 is G 2 or G 2 -G 3 , wherein G 2 is aryl or heteroaryl and G 3 is aryl or heteroaryl; and

R 3 is hydrogen or alkyl.

19. The compound or salt of claim 1 , wherein

L 2 is C(O)N(R 4 ), wherein R 4 is hydrogen;

R 2 is alkyl or G 2 or G 2 -G 3 , wherein G 2 is aryl or heteroaryl and G 3 is aryl or heteroaryl; and

R 3 is hydrogen or alkyl.

20. The compound or salt of claim 1 , wherein

L 2 is C(O) or S(O) 2 ;

R 2 is , —C(R c )(G 2 )(G 3 ), —(CR c R d ) p -G 2 , or —(CR c R d ) p —CH(G 2 )(G 3 );

Rc and Rd, at each occurrence, are each independently hydrogen or alkyl;

p is 1, 2, or 3;

G 2 and G 3 are independently aryl or heteroaryl; and

R 3 is hydrogen or alkyl.

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

tert-butyl(S)-4,4-dimethyl-1-oxo-1-((3aR,4S,6aS)-2-(5-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-ylamino)pentan-2-ylcarbamate;

isopropyl(S)-1-oxo-1-((3aR,4S,6aS)-2-(5-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-ylamino)pentan-2-ylcarbamate;

tert-butyl(S)-4,4-dimethyl-1-oxo-1-((3aR,4S,6aS)-2-(6-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-ylamino)pentan-2-ylcarbamate;

tert-butyl(S)-4,4-dimethyl-1-((3aR,4S,6aS)-2-(2-(methylsulfonyl)pyrimidin-5-yl)octahydrocyclopenta[c]pyrrol-4-ylamino)-1-oxopentan-2-ylcarbamate;

4-methyl-N 1 -{(3aR,4S,6aS)-2-[5-(trifluoromethyl)pyridine-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

4-methyl-N 1 -{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridine-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

4-methyl-N 1 -{(3aR,4S,6aS)-2-[2-(methylsulfonyl)pyridine-5-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -(cyclopropylmethyl)-4-methyl-N 1 -{(3aR,4S,6aS)-2-[5-trifluoromethyl)pyridine-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -(cyclopropylmethyl)-4-methyl-N 1 -{(3aR,4S,6aS)-2-[6-trifluoromethyl)pyridine-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -isopropyl-4-methyl-N 1 -{(3aR,4S,6aS)-2-[5-trifluoromethyl)pyridine-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -isopropyl-4-methyl-N 1 -{(3aR,4S,6aS)-2-[6-trifluoromethyl)pyridine-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -isopropyl-4-methyl-N 1 -{(3aR,4S,6aS)-2-[2-methylsulfonyl)pyrimidin-5-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

4-fluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzamide;

4-fluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzamide;

2-hydroxy-N-{(3aR,4S, 6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzamide;

2-fluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzamide;

3-fluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzamide;

3,4-difluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzamide;

3-chloro-4-fluoro-N-{(3aR,4S, 6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzamide;

(2S)-2-hydroxy-4-methyl-N-{(3aR,4S, 6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}pentanamide;

N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-1H-indole-2-carboxamide;

N-{(3aR,4S, 6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}quinoline-2-carboxamide;

N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-1H-indole-2-carboxamide;

5-(2-thienyl)-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-2-furamide;

4-methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-1H-pyrrole-2-carboxamide;

1-hydroxy-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}cyclopentanecarboxamide;

N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-4H-furo[3,2-b]pyrrole-5-carboxamide;

4-chloro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-1H-pyrrole-2-carboxamide;

5-methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-2-furamide;

3-hydroxy-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzamide;

(2R)-2-hydroxy-4-methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}pentanamide;

5-methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}pyrazine-2-carboxamide;

(2S)-2-hydroxy-3,3-dimethyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}butanamide;

5-methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-1,2-oxazole-4-carboxamide;

4,4,4-trifluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}butanamide;

3-cyclopropyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-1H-pyrazole-5-carboxamide;

cis-4-hydroxy-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}cyclohexanecarboxamide;

(2S)-3,3,3-trifluoro-2-hydroxy-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}propanamide;

4,4,4-trifluoro-3-hydroxy-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}butanamide;

N 2 ,4-dimethyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-norvalinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-norleucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

3-methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-valinamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(2S,3aS,7aS)-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}octahydro-1H-indole-2-carboxamide;

1-amino-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}cyclopentanecarboxamide;

4,4-difluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(4S)-4-fluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(2S)-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}piperidine-2-carboxamide;

N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-norvalinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-norleucinamide;

N 2 ,4-dimethyl-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

(2S,3aS,7aS)-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}octahydro-1H-indole-2-carboxamide;

(2S)-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-indoline-2-carboxamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[3-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

(3aR,4S,6aS)-N-(1H-indol-2-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-fluoro-1H-indol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-fluoro-1H-indol-2-yl)methyl]-2-[5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-fluoro-1H-indol-2-yl)methyl]-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-fluoro-1H-indol-2-yl)methyl]-2-[3-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-amine;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[3-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[2-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N-[(3aR,4S,6aS)-2-(2-fluorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N-[(3aR,4S,6aS)-2-(4-fluorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N-{(3aR,4S,6aS)-2-[4-fluoro-3-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[2-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[2-fluoro-3-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[3-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[4-fluoro-3-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[3-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

N-[(3aR,4S,6aS)-2-(3-chlorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N-[(3aR,4S,6aS)-2-(3-fluorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N 2 -methyl-N-[(3aR,4S,6aS)-2-(2-methylphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-leucinamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[4-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(4R)-N-[(3aR,4S,6aS)-2-(3-cyanophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-4-fluoro-L-prolinamide;

(4R)-N-[(3aR,4S,6aS)-2-(4-cyanophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-4-fluoro-L-prolinamide;

N-[(3aR,4S,6aS)-2-(2-chlorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N-{(3aR,4S,6aS)-2-[2-fluoro-3-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide;

N 2 -methyl-N-[(3aR,4S,6aS)-2-(3-methylphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-leucinamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[2-(trifluoromethyl)pyridin-4-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

N-[(3aR,4S,6aS)-2-(4-chlorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

(4R)-4-fluoro-N-[(3aR,4S,6aS)-2-(3-fluorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-prolinamide;

(4R)-4-fluoro-N-[(3aR,4S,6aS)-2-(4-fluorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-prolinamide;

(4R)-4-fluoro-N-[(3aR,4S,6aS)-2-(3-methylphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-prolinamide;

(4R)-N-[(3aR,4S,6aS)-2-(3-chlorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-4-fluoro-L-prolinamide;

(4R)-N-[(3aR,4S,6aS)-2-(4-chlorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-4-fluoro-L-prolinamide;

(4R)-4-fluoro-N-[(3aR,4S,6aS)-2-(3-methoxyphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-prolinamide;

N-[(3aR,4S,6aS)-2-(3-cyanophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N-[(3aR,4S,6aS)-2-(4-cyanophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N 2 -methyl-N-[(3aR,4S,6aS)-2-(4-methylphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-leucinamide;

(3aR,4S,6aS)-N-(4-methylbenzyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-fluoro-1H-indol-2-yl)methyl]-2-{[3-(trifluoromethyl)phenyl]sulfonyl}octahydrocyclopenta[c]pyrrol-4-amine;

(4R)-N-[(3aR,4S,6aS)-2-(2-cyanophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-4-fluoro-L-prolinamide;

(4R)-4-fluoro-N-[(3aR,4S,6aS)-2-(4-methylphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-prolinamide;

(4R)-4-fluoro-N-[(3aR,4S,6aS)-2-(4-methoxyphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-prolinamide;

(3aR,4S,6aS)-N-[(5-fluoro-1H-indol-2-yl)methyl]-2-{[4-(trifluoromethyl)phenyl]sulfonyl}octahydrocyclopenta[c]pyrrol-4-amine;

(4R)-N-{(3aR,4S,6aS)-2-[5-(difluoromethyl)-3-thienyl]octahydrocyclopenta[c]pyrrol-4-yl}-4-fluoro-L-prolinamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[2-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

N-{(3aR,4S,6aS)-2-[3-fluoro-4-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide;

(4R)-4-fluoro-N-[(3aR,4S,6aS)-2-(2-methylphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-prolinamide;

(4R)-N-[(3aR,4S,6aS)-2-(2-chlorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-4-fluoro-L-prolinamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[3-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(4R)-4-fluoro-N-[(3aR,4S,6aS)-2-(2-fluorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-prolinamide;

(4R)-4-fluoro-N-[(3aR,4S,6aS)-2-(2-methoxyphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-L-prolinamide;

(3aR,4S,6aS)-N-(1H-pyrazol-5-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(3-methyl-1H-indol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-chloro-1H-indol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-{[3-(4-chlorophenyl)-1H-pyrazol-4-yl]methyl}-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-fluoro-3-methyl-1H-indol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-methoxy-3-methyl-1H-indol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-{[3-(2-thienyl)-1H-pyrazol-4-yl]methyl}-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(4-methyl-1H-imidazol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(7-methyl-1H-indol-3-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-{[3-(4-fluorophenyl)-1H-pyrazol-4-yl]methyl}-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-{[3-(4-methylphenyl)-1H-pyrazol-4-yl]methyl}-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(2-butyl-1H-imidazol-4-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-(1H-imidazol-2-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(2-methyl-1H-imidazol-4-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-(1H-imidazol-4-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-fluoro-1H-indol-3-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(3-chloro-1H-indol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-chloro-1H-indol-3-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-{[3-(4-methoxyphenyl)-1H-pyrazol-4-yl]methyl}-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(3-phenyl-1H-pyrazol-4-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-(1H-benzimidazol-2-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-(1H-indol-3-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-methoxy-1H-indol-3-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(6-fluoro-1H-indol-3-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-{[3-(3,5-difluorophenyl)-1H-pyrazol-4-yl]methyl}-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(2-phenyl-1H-imidazol-4-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(4-methoxy-1H-indol-3-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(6-fluoro-1H-benzimidazol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(4-chloro-1H-indol-3-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-(1H-pyrrolo[2,3-b]pyridin-2-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-(1H-1,2,3-triazol-4-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(3-methyl-1H-pyrazol-4-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-(1H-pyrazol-4-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

5-fluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-1H-indole-2-carboxamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[4-fluoro-2-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[2-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

4-chloro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzenesulfonamide;

2-chloro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzenesulfonamide;

3-fluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzenesulfonamide;

2-fluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzenesulfonamide;

3-chloro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzenesulfonamide;

4-fluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzenesulfonamide;

N 2 -{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-[(3aR,4S,6aS)-2-{4-[(trifluoromethyl)thio]phenyl}octahydrocyclopenta[c]pyrrol-4-yl-]-L-leucinamide;

N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzenesulfonamide;

1-(4-fluorophenyl)-3-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-urea;

3-chloro-4-fluoro-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}benzenesulfonamide;

1-tert-butyl-3-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-urea;

N 2 -methyl-N-[(3aR,4S,6aS)-2-{3-[(trifluoromethyl)thio]phenyl}octahydrocyclopenta[c]pyrrol-4yl]-L-leucinamide;

1-(4-chlorophenyl)-3-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-urea;

1-(3-chloro-4-fluorophenyl)-3-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-urea;

(3aR,4S,6aS)-N-[(5-fluoro-1H-indol-2-yl)methyl]-2-[3-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-fluoro-1H-indol-2-yl)methyl]-2-[4-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-amine;

1-(4-chlorophenyl)-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-methanesulfonamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[3-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-norvalinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-norvalinamide;

(3aR,4S,6aS)-N-[(1-methyl-1H-indol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-(thieno[2,3-c]pyridin-2-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)pyrimidin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[2-(trifluoromethyl)pyrimidin-4-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridazin-3-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

(3aR,4S,6aS)-N-[(1-methyl-1H-pyrazol-5-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(5-chloro-2-phenyl-1H-imidazol-4-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-(thieno[2,3-b]pyridin-2-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-(2,1,3-benzothiadiazol-4-ylmethyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

N-{(3aR,4S,6aS)-2-[3-(difluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide;

N-[(3aR,4S,6aS)-2-(2,3-difluorrophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

(3aR,4S,6aS)-N-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

tert-butyl methyl{(2S)-3-methyl-1-[(3aR,4S,6aS)-octahydrocyclopenta[c]pyrrol-4-ylamino]-1-oxobutan-2-yl}-carbamate;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-3-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)pyridin-3-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N-{(3aR,4S,6aS)-2-[4-fluoro-2-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide;

N 2 -methyl-N-{(3aS,4R,6aR)-2-[5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aS,4R,6aR)-2-[4-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aS,4R,6aR)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

(3aR,4S,6aS)-N-{[2-(4-chlorophenyl)-1,3-oxazol-4-yl]methyl}-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-({2-[4-(trifluoromethyl)phenyl]-1H-imidazol-4-yl}methyl)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-{[2-(4-fluorophenyl)-1,3-oxazol-4-yl]methyl}-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-{[4-(4-fluorophenyl)-1H-imidazol-2-yl]methyl}-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-{[4-(4-chlorophenyl)-1H-imidazol-2-yl]methyl}-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

(3aR,4S,6aS)-N-[(4-phenyl-1H-imidazol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-valinamide;

(3aR,4S,6aS)-N-[(5-fluoro-1-methyl-1H-indol-2-yl)methyl]-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-amine;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-serinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-allothreoninamide;

N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-glycinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-glycinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-alaninamide;

N 2 ,2-dimethyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-alaninamide;

(2S)-2-amino-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}butanamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-valinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[3-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-valinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[3-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-valinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-norvalinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-D-leucinamide;

N 2 -isopropyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-glycinamide;

(2S)-2-(isopropylamino)-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}butanamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-valinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-valinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)pyridin-3-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N-{(3aR,4S,6aS)-2-[3-bromo-5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[2-(trifluoromethyl)pyridin-3-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aS,4R,6aR)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-D-leucinamide;

N-{(3aR,4S,6aS)-2-[3-(difluoromethyl)-4-fluorophenyl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide;

N-{(3aR,4S,6aS)-2-[2-(difluorormethyl)-5-fluorophenyl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide;

N-{(3aR,4S,6aS)-2-[2-(difluorormethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide;

N-{(3aR,4S,6aS)-2-[4-fluoro-3-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide;

N-[(3aR,4S,6aS)-2-(3-chloro-4-fluorophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N-{(3aR,4S,6aS)-2-[2-fluoro-4-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide;

3-cyclopropyl-N 2 -methyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-alaninamide;

3-cyclopropyl-N-{(3aR,4S,6aS)-2-[4-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-alaninamide;

3-cyclopropyl-N 2 ,N 2 -dimethyl-N-{(3aR,4S,6aS)-2-[4-(trifluorornethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-alaninamide;

1-tert-butyl-3-{(3aR,4S,6aS)-2-[4-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-urea;

1-tert-butyl-3-{(3aR,4S,6aS)-2-[3-(trifluoromethoxy)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-urea;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(4R)-4-fluoro-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(4S)-4-fluoro-N-{(3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(4S)-4-fluoro-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)-2-thienyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

(4S)-4-fluoro-N-{(3aR,4S,6aS)-2-[2-(trifluoromethyl)-3-thienyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide;

N-[(3aR,4S,6aS)-2-(2-methoxyphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N-[(3aR,4S,6aS)-2-(3-methoxyphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N-[(3aR,4S,6aS)-2-(4-methoxyphenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N-[(3aR,4S,6aS)-2-(2-cyanophenyl)octahydrocyclopenta[c]pyrrol-4-yl]-N 2 -methyl-L-leucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[5-(trifluoromethyl)-2-thienyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide;

N 2 -methyl-N-{(3aR,4S,6aS)-2-[2-(trifluoromethyl)-3-thienyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide; and

N-{(3aR,4S,6aS)-2-[5-(difluoromethyl)-3-thienyl]octahydrocyclopenta[c]pyrrol-4-yl}-N 2 -methyl-L-leucinamide.

22. 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.

23. 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.

Assignments (2)
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 Aug 3, 2011
From: SEARLE, XENIA B.; YEUNG, MING C.; DIDOMENICO, STANLEY; STEWART, ANDREW O.; DARCZAK, DARIA; SCHRIMPF, MICHAEL; ROZEMA, MICHAEL J.
To: ABBOTT LABORATORIES
Reel/Frame 026694/0320 →