US2020102311A1PendingUtilityA1
Monoacylglycerol Lipase Modulators
Est. expirySep 28, 2038(~12.2 yrs left)· nominal 20-yr term from priority
A61K 31/437C07D 471/18C07D 519/00C07D 471/04A61P 25/18A61P 25/24A61P 29/00A61P 27/02A61P 35/00
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Claims
Abstract
wherein R2, R3 R4, R5 and R6 are defined herein.
Claims
exact text as granted — not AI-modified1 . A compound, having the structure of Formula (I):
wherein
R 2 is selected from the group consisting of:
(a)
(b) 6-membered heteroaryl selected from the group consisting of: pyridazin-4-yl; pyrazin-2-yl; pyrimidinyl; pyrimidinyl substituted with C 1-4 alkyl or OC 1-4 alkyl; and pyridinyl, wherein the pyridinyl is substituted with one or two substituents each independently selected from the group consisting of: halo, C 1-4 alkyl, OC 1-4 alkyl, OC 1-4 haloalkyl, C 3-6 cycloalkyl, NH 2 , CN, N(CH 3 ) 2 ,
(c) 5-membered heteroaryl selected from the group consisting of:
(d) 5,6-fused bicyclic heteroaryl or 6,5-fused bicyclic heteroaryl selected from the group consisting of:
(e) 6,6-fused bicyclic heteroaryl selected from the group consisting of:
and
(f)
wherein
R a is selected from the group consisting of: H, halo, C 1-4 alkyl, OC 1-4 alkyl, C 1-4 haloalkyl and OC 1-4 haloalkyl;
R a1 is selected from the group consisting of: C 1-4 alkyl, OC 1-4 alkyl, OC 1-4 haloalkyl, N(C═O)CH 3 , oxazol-2-yl, pyrimidin-2-yl, and 5-membered heteroaryl ring containing two, three, or four nitrogen members, wherein the 5-membered heteroaryl ring is optionally substituted with one R a member;
R b is H or C 1-4 akyl;
R c is H or C 1-4 haloalkyl;
R d is H or halo;
R e is selected from the group consisting of: H, halo, C 1-4 akyl, C 1-4 haloalkyl, OC 1-4 alkyl, and C 3-6 cycloalkyl;
R f is selected from the group consisting of: H, C 1-4 alkyl, CH 2 CH 2 OH, C 1-4 haloalkyl, cyclopropyl, phenyl, and phenyl substituted with CF 3 ;
R g is selected from the group consisting of: H, OC 1-4 alkyl and C 1-4 haloalkyl;
R i is H, halo, C 1-4 alkyl, C 1-4 haloalkyl, OH, OC 1-4 alkyl, OC 1-4 haloalkyl, C 3-6 cycloalkyl;
R j is selected from the group consisting of: H, halo, OCH 3 , OH, NH 2 , and NO 2 ;
R 3 is selected from the group consisting of:
(g) phenyl, wherein phenyl is independently substituted with one, two, or three members selected from the group consisting of: halo, C 1-4 alkyl, C 1-4 haloalkyl, and OC 1-4 alkyl;
(h) 5-(trifluoromethyl)-2-thienyl or 1-methylindol-2-yl; and
(i) cyclopropyl; and
R 4 is C 1-4 alkyl or C 3-4 cycloalkyl;
and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers thereof.
2 . A compound as claimed in claim 1 , wherein R 2 is
where R a is H, halo, C 1-4 alkyl, or OC 1-4 alkyl; and R a1 is C 1-4 alkyl, OC 1-4 alkyl, OC 1-4 haloalkyl, or (C═O)NHCH 3 .
3 . A compound as claimed in claim 1 , wherein R 2 is
4 . A compound as claimed in claim 1 , wherein R 2 is:
where R a is H, halo, C 1-4 alkyl, OC 1-4 alkyl, or C 1-4 haloalkyl; and R a1 is
5 . A compound as claimed in claim 4 , wherein R a1 is:
6 . A compound as claimed in claim 4 , wherein R a is: H, Cl, F, CH 3 , CF 3 , or OCH 3 .
7 . A compound as claimed in claim 4 , wherein R b is: H or CH 3 .
8 . A compound as claimed in claim 4 , wherein R c is: H or CF 3 .
9 . A compound as claimed in claim 4 , wherein R d is: H, Cl, or F.
10 . A compound as claimed in claim 1 , wherein R 2 is:
11 . A compound as claimed in claim 1 , wherein R 2 is:
12 . A compound as claimed in claim 1 , wherein R 2 is:
13 . A compound as claimed in claim 1 , wherein R 2 is:
14 . A compound as claimed in claim 1 , wherein R 2 is:
15 . A compound as claimed in claim 1 , wherein R 2 is
wherein R a is H, Cl, Br, F, or OCH 3 , and R a1 is OCH 3 or
16 . A compound as claimed in claim 1 , wherein R 2 is:
17 . A compound as claimed in claim 1 , wherein R 2 is:
18 . A compound as claimed in claim 1 , wherein R 2 is:
19 . A compound as claimed in claim 1 , wherein R 2 is:
20 . A compound as claimed in claim 1 , wherein R 2 is:
21 . A compound as claimed in claim 1 , wherein R 2 is:
22 . A compound as claimed in claim 1 , wherein R 2 is:
23 . A compound as claimed in claim 22 , wherein R e is independently selected from the group consisting of: H, halo, C 1-4 akyl, C 1-4 haloalkyl, OC 1-4 alkyl, and cyclopropyl.
24 . A compound as claimed in claim 22 , wherein R f is selected from the group consisting of: H, C 1-4 alkyl, CH 2 CH 2 OH, CH 2 CF 3 , cyclopropyl, phenyl, and phenyl substituted with CF 3 .
25 . A compound as claimed in claim 22 , wherein R g is H, OCH 3 or CF 3 .
26 . A compound as claimed in claim 1 , wherein R 2 is:
27 . A compound as claimed in claim 1 , wherein R 2 is
28 . A compound as claimed in claim 27 , wherein R a is independently selected from the group consisting of: H, Cl, F, C 1-4 alkyl, OC 1-4 alkyl, and C 1-4 haloalkyl; and R b is CH 3 or CH(CH 3 ) 2 .
29 . A compound as claimed in claim 1 , wherein R 2 is:
30 . A compound as claimed in claim 1 , wherein R 2 is:
31 . A compound as claimed in claim 1 , wherein R 2 is:
32 . A compound as claimed in claim 1 , wherein R 2 is:
33 . A compound as claimed in claim 1 , wherein R 2 is:
34 . A compound as claimed in claim 1 , wherein R 2 is:
35 . A compound as claimed in claim 1 , wherein R 2 is:
36 . A compound as claimed in claim 1 , wherein R 2 is:
37 . A compound as claimed in claim 1 , wherein R 2 is:
38 . A compound as claimed in claim 1 , wherein R 2 is:
39 . A compound as claimed in claim 1 , wherein R 2 is:
40 . A compound as claimed in claim 1 , wherein R 2 is:
41 . A compound as claimed in claim 1 , wherein R 2 is:
42 . A compound as claimed in claim 1 , wherein R 3 is:
43 . A compound as claimed in claim 1 , wherein R 3 is cyclopropyl and R 4 is CH 3 .
44 . A compound as claimed in claim 1 , wherein R 3 is 5-(trifluoromethyl)-2-thienyl or 1-methylindol-2-yl; and R 4 is CH 3 .
45 . A compound as claimed in claim 1 , wherein R 3 is 3-chlorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl, 3,4-difluorophenyl, and 4-chloro-3-fluorophenyl.
46 . A compound as claimed in claim 1 , wherein R 4 is CH 3 .
47 . A compound as claimed in claim 1 , wherein R 4 is cyclopropyl.
48 . A compound as claimed in claim 1 , wherein R 2 is
wherein R a is F, Cl, or OCH 3 , R a1 is OCH 3 , CH 3 , or 2H-1,2,3-triazol-2-yl and R 4 is CH 3 .
49 . The compound of claim 1 , having the structure of Formula (1A):
wherein
R 2 is selected from the group consisting of:
R 4 is CH 3 or cyclopropyl;
R q is halo, or CHF 2 ; and
n is 0, 1, or 2;
and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers thereof.
50 . The compound of claim 1 , having the structure of Formula (1B):
wherein
R 2 is phenyl optionally independently substituted with one or two members selected from the group consisting of: halo, C 1-4 alkyl, C 1-4 haloalkyl, OC 1-4 alkyl, OC 1-4 haloalkyl, NH(C═O)(CH 3 ),
wherein
R a is selected from the group consisting of: H, halo, C 1-4 alkyl, OC 1-4 alkyl, and C 1-4 haloalkyl;
R b is C 1-4 akyl;
R c is H or CF 3 ;
R d is H or halo;
each R q is independently selected from the group consisting of: Cl, F, CF 3 , and OCH 3 ; and
n is 0, 1, 2, or 3;
and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers thereof.
51 . The compound of claim 1 , having the structure of Formula (1C):
wherein
R 2 is selected from the group consisting of:
(a) 5-membered heteroaryl selected from the group consisting of:
and
(b) 6-membered heteroaryl selected from the group consisting of: pyridazin-4-yl; pyrazin-2-yl; pyrimidinyl; pyrimidinyl substituted with C 1-4 alkyl or OC 1-4 alkyl; and pyridinyl, wherein the pyridinyl is substituted with one or two substituents each independently selected from the group consisting of: halo, C 1-4 alkyl, OC 1-4 alkyl, OC 1-4 haloalkyl, cyclopropyl, NH 2 , CN, N(CH 3 ) 2 ,
wherein
R a is selected from the group consisting of: H, halo, OC 1-4 alkyl, and C 1-4 haloalkyl;
R b is C 1-4 akyl;
R e is selected from the group consisting of: F, C 1-4 akyl, CF 2 H, CF 3 , OCH 3 , and cyclopropyl;
R f is selected from the group consisting of: H, C 1-4 alkyl, cyclopropyl, and phenyl;
R g is H or CF 3 ; and
R 3 is phenyl substituted with one, two, or three members each independently selected from the group consisting of: Cl and F; and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers thereof.
52 . A compound of claim 51 , wherein R 2 is:
53 . A compound of claim 51 , wherein R 2 is:
54 . The compound of claim 1 , having the structure of Formula (ID):
wherein
Ring A is selected from the group consisting of:
(a) 6,6-fused bicyclic heteroaryl selected from the group consisting of:
and
(b) 5,6-fused bicyclic heteroaryl or 6,5-fused bicyclic heteroaryl selected from the group consisting of:
wherein
R a is selected from the group consisting of: H, Cl, F, CH 3 , OCH 3 , CF 3 , and CF 2 H;
R b is H or CH 3 ;
R c is H or CF 3 ;
R d is selected from the group consisting of: H, Cl, and F;
R e is selected from the group consisting of: H, C 1-4 alkyl, and cyclopropyl;
R i is selected from the group consisting of: H, Cl, Br, CH 3 , CF 3 , OH, and OCH 2 CH 2 F;
R j is selected from the group consisting of: H, halo, OCH 3 , OH, NH 2 , and NO 2 ; and
R 3 is cyclopropyl, 1-methyl-1H-indol-2-yl, or phenyl substituted with one, two, or three members each independently selected from the group consisting of: Cl, F, CH 3 , OCH 3 , and CF 3 ;
and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers thereof.
55 . A compound of claim 54 , wherein R 3 is:
56 . A compound of claim 54 , wherein Ring A is:
57 . A compound of claim 54 wherein Ring A is:
58 . A compound selected from the group consisting of:
racemic-((5R,9S)-2-Methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl)methanone; ((5R,9S)-3-Cyclopropyl-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl)methanone; racemic-(2-Chloro-3-methoxyphenyl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-Chloro-3-methoxyphenyl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; (2-Chloro-3-methoxyphenyl) ((5S,9R)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; racemic-(2-(1H-1,2,4-Triazol-1-yl) phenyl)((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(3-(4H-1,2,4-Triazol-4-yl) phenyl)((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(4-(1H-1,2,4-Triazol-1-yl) phenyl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(3-(1H-Imidazol-1-yl) phenyl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; racemic-(1-Methyl-1H-1,2,4-triazol-3-yl)((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(5-Chloro-1-methyl-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(5-Methoxy-1-methyl-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(4-Bromo-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(5-Cyclopropyl-1-methyl-1H-pyrazol-4-yl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-((5R,9S)-2-Methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (1-phenyl-1H-1,2,4-triazol-3-yl)methanone; racemic-((5R,9S)-2-Methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (1-phenyl-1H-pyrazol-3-yl)methanone; racemic-(5-Methoxy-1-phenyl-1H-pyrazol-3-yl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; racemic-(1-Methyl-1H-indol-4-yl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(5-Chloro-1H-indol-6-yl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; racemic-(7-Methyl-1H-indazol-5-yl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; racemic-(1-Methyl-1H-pyrrolo[2,3-b] pyridin-4-yl)((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(4-Chloro-1H-pyrrolo[2,3-b] pyridin-5-yl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(4-Fluoro-1H-pyrrolo[2,3-b] pyridin-5-yl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(1-Methyl-1H-pyrrolo[2,3-b] pyridin-3-yl)((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-[1,2,4] Triazolo[1,5-a] pyridin-5-yl((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(4-Chloroquinolin-6-yl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; racemic-(4-Hydroxyquinolin-6-yl) ((5R,9S)-2-methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; racemic-((5R,9S)-2-Methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinoxalin-5-yl)methanone; racemic-((5R,9S)-2-Methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinoxalin-6-yl) methanone; racemic-((5R,9S)-2-Methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinazolin-6-yl) methanone; racemic-((5R,9S)-2-Methyl-3-phenyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-(trifluoromethyl)-1,8-naphthyridin-3-yl)methanone; racemic-(2-Chloro-3-methoxyphenyl) ((5R,9S)-3-(4-fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; (2-(2H-1,2,3-Triazol-2-yl)phenyl)((5R,9S)-3-(4-fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(1,4-Dimethyl-1H-pyrazol-3-yl)((5R,9S)-3-(4-fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(4-Fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)methanone; racemic-((5R,9S)-3-(4-Fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl) methanone; ((5R,9S)-3-(4-Fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl) methanone; racemic-(2-Chloro-3-methoxyphenyl) ((5R,9S)-3-(3-fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; racemic-((5R,9S)-3-(3-Fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (1-phenyl-1H-1,2,4-triazol-3-yl) methanone; ((5R,9S)-3-(3-Fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (furo[3,2-b] pyridin-6-yl) methanone; racemic-((5R,9S)-3-(3-Fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl)methanone; ((5S,9R)-3-(3-Fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl) methanone; ((5R,9S)-3-(3-Fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl) methanone; racemic-((5R,9S)-2-Cyclopropyl-3-(3-fluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl)methanone; (3-(1H-1,2,4-Triazol-1-yl)phenyl)((5R,9S)-3-(3-chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-(1H-Pyrazol-4-yl)phenyl)((5R,9S)-3-(3-chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-(1H-Pyrazol-1-yl)phenyl)((5R,9S)-3-(3-chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-(1H-Tetrazol-1-yl)phenyl)((5R,9S)-3-(3-chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-Chloro-5-(4H-1,2,4-triazol-4-yl)phenyl)((5R,9S)-3-(3-chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-(4H-1,2,4-Triazol-4-yl)phenyl)((5R,9S)-3-(3-chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3-Chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-isopropyl-1H-1,2,4-triazol-3-yl)methanone; ((5R,9S)-3-(3-Chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-(2-fluorophenyl)-1H-1,2,4-triazol-3-yl)methanone; ((5R,9S)-3-(3-Chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-(pyridin-2-yl)-1H-1,2,4-triazol-3-yl)methanone; ((5R,9S)-3-(3-Chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-(3-fluorophenyl)-1H-1,2,4-triazol-3-yl)methanone; (1-(3-Chlorophenyl)-1H-1,2,4-triazol-3-yl)((5R,9S)-3-(3-chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3-Chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)methanone; ((5R,9S)-3-(3-Chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methyl-1-(3-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)methanone; ((5R,9S)-3-(3-Chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-(3-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)methanone; (1-Benzyl-1H-1,2,4-triazol-3-yl)((5R,9S)-3-(3-chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; Benzo[d]isoxazol-3-yl((5R,9S)-3-(3-chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3-chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-methyl-1H-indazol-3-yl)methanone; racemic-((5R,9S)-3-(3-Chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl) methanone; ((5R,9S)-3-(3-Chlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinoxalin-6-yl) methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(4-(2-fluoroethoxy)quinolin-6-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(3-(2-fluoroethoxy)phenyl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(3-(2-(fluoro-18F)ethoxy)phenyl)methanone; racemic-(2-(2H-1,2,3-Triazol-2-yl) phenyl) ((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; (2-(1H-1,2,4-Triazol-5-yl) phenyl) ((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; (2-(5-Chloro-1H-1,2,4-triazol-3-yl)phenyl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(3-(1-methyl-1H-pyrazol-4-yl)phenyl)methanone; (3-(4H-1,2,4-Triazol-4-yl) phenyl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (3-fluoro-2-(2H-1,2,3-triazol-2-yl) phenyl) methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(3-fluoro-2-(oxazol-2-yl)phenyl)methanone; racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-(pyrimidin-2-yl)phenyl)methanone; racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methoxy-1-methyl-1H-pyrazol-4-yl)methanone; racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-ethyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)methanone; racemic-(5-Cyclopropyl-1H-pyrazol-4-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(5-Cyclopropyl-1-(2-hydroxyethyl)-1H-pyrazol-4-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(3-Cyclopropyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(5-Cyclopropyl-1-phenyl-1H-pyrazol-4-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-(5-Cyclopropyl-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methyl-1-phenyl-1H-1,2,4-triazol-3-yl)methanone; racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-(4-fluorophenyl)-5-methyl-H-1,2,4-triazol-3-yl)methanone; racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-ethyl-1-phenyl-1H-1,2,4-triazol-3-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-fluoropyridin-4-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methoxypyridin-3-yl)methanone; (5-Aminopyridin-2-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methoxybenzofuran-2-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (2-methylbenzo[d]oxazol-6-yl) methanone; (2-Aminobenzo[d]oxazol-6-yl) ((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (furo[3,2-b] pyridin-2-yl) methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(furo[3,2-c]pyridin-4-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (1-methyl-1H-pyrazolo[3,4-b] pyridin-3-yl) methanone; racemic-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl) methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-6-yl)methanone; ((5S,9R)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl) methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (isoquinolin-3-yl) methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-7-yl)methanone; (4-Bromoquinolin-6-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Bromoquinolin-6-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (8-Bromoquinolin-6-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-Chloroquinolin-6-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(8-fluoroquinolin-5-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(8-fluoroquinolin-6-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(2-(trifluoromethyl)quinolin-6-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(8-hydroxyquinolin-6-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methoxyquinolin-3-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(8-nitroquinolin-6-yl)methanone; (8-Aminoquinolin-6-yl)((5R,9S)-3-(3,5-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinazolin-7-yl) methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinoxalin-6-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(quinazolin-6-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(2-methylquinoxalin-6-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (7-fluoroquinoxalin-6-yl) methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (1,6-naphthyridin-5-yl) methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1,8-naphthyridin-3-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1,8-naphthyridin-4-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1,7-naphthyridin-4-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1,6-naphthyridin-4-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (1,5-naphthyridin-2-yl) methanone; 6-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazole-10-carbonyl)-1-(2-fluoroethyl)quinolin-4(1H)-one; 6-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazole-10-carbonyl)-4-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)methanone; (2-(2H-1,2,3-Triazol-2-yl)phenyl)((5R,9S)-3-(3,4-difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; racemic-((5R,9S)-3-(3,4-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl) methanone; ((5R,9S)-3-(3,4-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(quinolin-6-yl)methanone; racemic-((5R,9S)-3-(3,4-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinoxalin-6-yl) methanone; ((5R,9S)-3-(3-Fluoro-5-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinoxalin-6-yl) methanone; ((5R,9S)-3-(4-Chloro-3-fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinoxalin-6-yl) methanone; ((5R,9S)-3-(3-Chloro-4-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinoxalin-6-yl) methanone; (2-(2H-1,2,3-Triazol-2-yl)phenyl)((5R,9S)-3-(3-chloro-4-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3-Chloro-4-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (1-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)methanone; ((5R,9S)-3-(3-Chloro-4-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-6-yl)methanone; ((5R,9S)-3-(3-Chloro-5-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-methylbenzo[d]oxazol-6-yl)methanone; ((5R,9S)-3-(3-Chloro-5-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-6-yl)methanone; ((5R,9S)-3-(3-Chloro-5-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinoxalin-6-yl)methanone; ((5R,9S)-3-(3,5-Dimethoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-methylbenzo[d]oxazol-6-yl)methanone; ((5R,9S)-3-(3,5-Dimethoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinoxalin-6-yl)methanone; (3-(4H-1,2,4-triazol-4-yl)phenyl)((5R,9S)-3-(3,5-dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3,5-Dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)methanone; ((5R,9S)-3-(3,5-Dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methoxy-1-methyl-1H-pyrazol-4-yl)methanone; (5-Cyclopropyl-1-methyl-1H-pyrazol-4-yl)((5R,9S)-3-(3,5-dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3,5-Dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-phenyl-1H-1,2,4-triazol-3-yl)methanone; ((5R,9S)-3-(3,5-Dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methoxypyridin-3-yl)methanone; ((5R,9S)-3-(3,5-Dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(6-methyl-3-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)methanone; ((5R,9S)-3-(3,5-Dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-methylbenzo[d]oxazol-6-yl)methanone; ((5R,9S)-3-(3,5-Dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(furo[3,2-b]pyridin-2-yl)methanone; ((5R,9S)-3-(3,5-Dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(imidazo[1,5-a]pyridin-8-yl)methanone; ((5R,9S)-3-(3,5-Dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(imidazo[1,2-a]pyridin-3-yl)methanone; (4-Methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3,5-Dichlorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinoxalin-6-yl)methanone; racemic-((5R,9S)-3-(3-(Difluoromethyl)-4-fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl) methanone; racemic-((5R,9S)-3-(3-(Difluoromethyl)-4-fluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinoxalin-6-yl) methanone; ((5R,9S)-3-(3-Fluoro-5-(trifluoromethyl) phenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinoxalin-6-yl) methanone; (3-Chloro-5-methoxyphenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; N-(3-Methoxy-5-((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazole-10-carbonyl) phenyl)acetamide; (3-(4H-1,2,4-Triazol-4-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-(4H-1,2,4-Triazol-4-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Fluoro-2-(1H-1,2,4-triazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-Fluoro-2-(1H-1,2,4-triazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Fluoro-2-(1H-1,2,4-triazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-Methyl-2-(1H-1,2,4-triazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Methyl-2-(1H-1,2,4-triazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-(1H-1,2,4-Triazol-1-yl)-5-(trifluoromethyl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)phenyl)methanone; (2-(1H-Imidazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Fluoro-2-(1H-pyrazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-(1-Methyl-1H-pyrazol-4-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-(4-Fluoro-1H-pyrazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(3-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methanone; (3-(4-Methoxy-1H-pyrazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(3-(3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methanone; (3-(2H-1,2,3-Triazol-2-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Fluoro-2-(2H-1,2,3-triazol-2-yl) phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-Methoxy-2-(2H-1,2,3-triazol-2-yl) phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-(2H-1,2,3-Triazol-2-yl)-4-(trifluoromethyl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-(2H-1,2,3-Triazol-2-yl)-5-(trifluoromethyl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-(1H-1,2,3-Triazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Methoxy-2-(1H-1,2,3-triazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)methanone; (3,4-Dihydro-2H-pyrano[3,2-b]pyridin-7-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6,7-Dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)methanone; (6,7-Dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-methyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)methanone; (1-(tert-Butyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Ethyl-1-phenyl-1H-1,2,4-triazol-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-phenyl-5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)methanone; (5-Methoxy-1-phenyl-1H-1,2,4-triazol-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (1-(3-Fluorophenyl)-1H-1,2,4-triazol-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (1-(4-Fluorophenyl)-5-methyl-1H-1,2,4-triazol-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (1-(2-Methoxyphenyl)-1H-1,2,4-triazol-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (1-(3-Methoxyphenyl)-1H-1,2,4-triazol-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-Methoxypyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-Methoxypyridin-2-yl) ((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-Methoxypyridin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Methoxypyridin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-Methoxypyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Isopropoxypyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(6-(trifluoromethoxy)pyridin-2-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-(trifluoromethoxy)pyridin-2-yl)methanone; 6-((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazole-10-carbonyl) picolinonitrile; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(pyrazin-2-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(pyrimidin-4-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(pyridazin-4-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(pyrimidin-5-yl)methanone; (5-(1H-Pyrazol-10-yl)pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-(1H-Pyrazol-10-yl)pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-(1H-Pyrrol-1-yl) pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)methanone; (6-(1H-Imidazol-1-yl) pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)methanone; (6-Methyl-3-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(5-(pyrrolidin-1-yl)pyridin-3-yl)methanone; 1-(5-((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazole-10-carbonyl) pyridin-3-yl) pyrrolidin-2-one; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-morpholinopyridin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-methylindolizin-6-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (2-methylbenzo[d]oxazol-6-yl) methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(pyrazolo[1,5-a]pyridin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(5-methylpyrazolo[1,5-a]pyridin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(pyrazolo[1,5-a]pyridin-5-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(pyrazolo[1,5-a]pyridin-6-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(pyrazolo[1,5-a]pyridin-2-yl)methanone; Imidazo[1,2-a]pyridin-5-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; Imidazo[1,5-a]pyridin-5-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; Imidazo[1,5-a]pyridin-6-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; Imidazo[1,2-a]pyridin-6-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(7-methylimidazo[1,2-a]pyridin-3-yl)methanone; (1-Methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (1-Methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)((R, 9 S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(pyrrolo[1,2-b]pyridazin-5-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(pyrrolo[1,2-a]pyrazin-8-yl)methanone; (4-Methoxy-1-methyl-1H-indazol-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (1-Methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(pyrazolo[1,5-b]pyridazin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (pyrazolo[1,5-a]pyrimidin-2-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(pyrazolo[1,5-a]pyrimidin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(6-methylpyrazolo[1,5-a]pyrimidin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(pyrazolo[1,5-a]pyrimidin-5-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(pyrazolo[1,5-a]pyrazin-3-yl)methanone; Imidazo[1,2-b]pyridazin-6-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; Imidazo[1,2-b]pyridazin-3-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; [1,2,4]Triazolo[1,5-a]pyridin-7-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)methanone; Imidazo[1,2-a]pyrimidin-3-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-4-yl)methanone; Isoquinolin-1-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl) methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(quinolin-7-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(quinazolin-4-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinoxalin-6-yl) methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(2-methylquinoxalin-6-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(quinoxalin-2-yl)methanone; Cinnolin-3-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; Cinnolin-6-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1,5-naphthyridin-2-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1,5-naphthyridin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1,6-naphthyridin-8-yl)methanone; (2-(2H-1,2,3-Triazol-2-yl)phenyl)((5R,9S)-3-(3,5-difluoro-4-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3,5-Difluoro-4-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)methanone; ((5R,9S)-3-(3,5-Difluoro-4-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-6-yl)methanone; (2-(2H-1,2,3-Triazol-2-yl)phenyl)((5R,9S)-3-(3,5-difluoro-4-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3,4-Difluoro-5-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (1-methyl-1H-pyrazolo[3,4-b] pyridin-3-yl)methanone; ((5R,9S)-3-(3,4-Difluoro-5-methoxyphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-6-yl)methanone; ((5R,9S)-2-Methyl-3-(1-methyl-1H-indol-2-yl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl) (quinolin-6-yl)methanone; racemic-((5R,9S)-2-Methyl-3-(5-(trifluoromethyl)thiophen-2-yl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-6-yl)methanone; (4-Methoxyphenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-Fluoro-4-methylphenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-Fluoro-4-methoxyphenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Fluoro-5-(1H-pyrazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Fluoro-5-(4H-1,2,4-triazol-4-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-Fluoro-3-(4H-1,2,4-triazol-4-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(4-methyl-3-(4H-1,2,4-triazol-4-yl)phenyl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(3-methyl-5-(4H-1,2,4-triazol-4-yl)phenyl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-methyl-3-(4H-1,2,4-triazol-4-yl)phenyl)methanone; (2-(2H-1,2,3-Triazol-2-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-Fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-(2H-1,2,3-Triazol-2-yl)-3-(trifluoromethyl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-(4-Methyl-2H-1,2,3-triazol-2-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-(4-(trifluoromethyl)-2H-1,2,3-triazol-2-yl)phenyl)methanone; (5-Methoxy-2-(1H-1,2,4-triazol-1-yl)phenyl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-(4-(trifluoromethyl)-1H-1,2,3-triazol-1-yl)phenyl)methanone; (6-Isopropylpyrimidin-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-Methoxypyrimidin-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-(Dimethylamino)pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Methoxy-4-methylpyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-Methoxy-5-methylpyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Fluoro-6-methoxypyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Fluoro-2-methoxypyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5,6-Dimethoxypyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5,6-Dimethoxypyridin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Chloro-2-methoxypyridin-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Chloro-6-methoxypyridin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-Chloro-2-methylpyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-Chloro-5-methylpyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Chloro-5-fluoropyridin-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-Cyclopropyl-2-methylpyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; 1-(5-((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazole-10-carbonyl)pyridin-2-yl)cyclopropane-1-carbonitrile; (2-(1H-Pyrazol-1-yl)pyridin-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-(1H-Pyrazol-1-yl)pyridin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-(1H-Pyrazol-1-yl)pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-(1H-Pyrazol-1-yl)pyridin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-Methyl-3-(1H-pyrazol-1-yl)pyridin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-Methoxy-5-(1H-pyrazol-1-yl)pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-Methyl-3-(1H-1,2,4-triazol-1-yl)pyridin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-(4H-1,2,4-Triazol-4-yl)pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-(4H-1,2,4-Triazol-4-yl)pyridin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(6-methyl-4-(4H-1,2,4-triazol-4-yl)pyridin-2-yl)methanone; (5-(2H-1,2,3-Triazol-2-yl)pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-(2H-1,2,3-Triazol-2-yl)pyridin-2-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(6-methyl-4-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)methanone; (1,5-Dimethyl-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-Ethyl-1-methyl-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(1,3,5-trimethyl-1H-pyrazol-4-yl)methanone; (5-Methoxy-1-methyl-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Methoxy-1-methyl-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Fluoro-1,5-dimethyl-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (5-(Difluoromethyl)-1-methyl-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (1-Cyclopropyl-5-methyl-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (1-Cyclopropyl-3-methyl-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (3-Cyclopropyl-1-methyl-1H-pyrazol-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; Indolizin-7-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (4-Fluoropyrazolo[1,5-a]pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-Fluoropyrazolo[1,5-a]pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(7-methylpyrazolo[1,5-a]pyridin-3-yl)methanone; (4-Methoxypyrazolo[1,5-a]pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (6-Methoxypyrazolo[1,5-a] pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)methanone; Imidazo[1,5-a]pyridin-7-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methylimidazo[1,5-a]pyridin-6-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(3-methylimidazo[1,5-a]pyridin-6-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methylimidazo[1,2-a]pyridin-6-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(7-methylimidazo[1,2-a]pyridin-5-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(3-methylimidazo[1,2-a]pyridin-5-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(3-methylimidazo[1,2-a]pyridin-6-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(2-methylimidazo[1,2-a]pyridin-6-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(2-methylimidazo[1,2-a]pyridin-5-yl)methanone; Imidazo[1,2-a]pyridin-3-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (7-Fluoroimidazo[1,2-a]pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (7-Chloroimidazo[1,2-a]pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-methylimidazo[1,2-a] pyridin-3-yl) methanone; (2,7-Dimethylimidazo[1,2-a]pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-3-(3-Fluoro-5-methylphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(2-methylimidazo[1,2-a]pyridin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methylimidazo[1,2-a]pyridin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(7-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)methanone; (2-(Difluoromethyl)imidazo[1,2-a]pyridin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2-Methyl-2H-indazol-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (2,7-Dimethylpyrazolo[1,5-a]pyrimidin-5-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(7-methylpyrazolo[1,5-a]pyrimidin-6-yl)methanone; (5-Isopropyl-3-methylpyrazolo[1,5-a]pyrimidin-7-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2,3,5-trimethylpyrazolo[1,5-a]pyrimidin-7-yl)methanone; (7-Cyclopropyl-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-methylpyrazolo[1,5-b]pyridazin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-methylimidazo[1,2-a]pyrazin-8-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2,5,8-trimethylimidazo[1,2-a]pyrazin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-methylimidazo[1,2-b]pyridazin-3-yl)methanone; (2,7-Dimethylimidazo[1,2-b]pyridazin-3-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(3-methyl-3H-imidazo[4,5-b]pyridin-7-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-1-yl)(3-methyl-3H-imidazo[4,5-b]pyridin-6-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)methanone; (1-Methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; (1-Methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; [1,2,4]Triazolo[4,3-a]pyridin-7-yl((5R,9S)-2-methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(3-methylimidazo[1,5-a]pyrazin-1-yl)methanone; ((5R,9S)-3-(3-Fluoro-5-methylphenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-6-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(4-methylquinolin-6-yl)methanone; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2-hydroxyquinolin-6-yl)methanone; 6-((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazole-10-carbonyl) quinoline 1-oxide; ((5R,9S)-3-(3,5-Difluorophenyl)-2-methyl-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinolin-6-yl-4-t)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(6-methylquinazolin-4-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinoxalin-6-yl-2-d)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(quinoxalin-6-yl-2,3-d2)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-3-yl)methanone; ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-3-yl)methanone; and ((5R,9S)-2-Methyl-3-(3,4,5-trifluorophenyl)-4,5,6,7,8,9-hexahydro-2H-5,9-epiminocycloocta[c]pyrazol-10-yl)(2,6,6-trimethyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-3-yl)methanone; and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers thereof.
59 . A compound selected from the group consisting of:
60 . A pharmaceutical composition comprising:
(A) a therapeutically effective amount of at least one compound of Formula (I):
wherein
R 2 is selected from the group consisting of:
(a)
(b) 6-membered heteroaryl selected from the group consisting of: pyridazin-4-yl; pyrazin-2-yl; pyrimidinyl; pyrimidinyl substituted with C 1-4 alkyl or OC 1-4 alkyl; and pyridinyl, wherein the pyridinyl is substituted with one or two substituents each independently selected from the group consisting of: halo, C 1-4 alkyl, OC 1-4 alkyl, OC 1-4 haloalkyl, C 3-6 cycloalkyl, NH 2 , CN, N(CH 3 ) 2 ,
(c) 5-membered heteroaryl selected from the group consisting of:
(d) 5,6-fused bicyclic heteroaryl or 6,5-fused bicyclic heteroaryl selected from the group consisting of:
(e) 6,6-fused bicyclic heteroaryl selected from the group consisting of:
and
(f)
wherein
R a is selected from the group consisting of: H, halo, C 1-4 alkyl, OC 1-4 alkyl, C 1-4 haloalkyl and OC 1-4 haloalkyl;
R a1 is selected from the group consisting of: C 1-4 alkyl, OC 1-4 alkyl, OC 1-4 haloalkyl, N(C═O)CH 3 , oxazol-2-yl, pyrimidin-2-yl, and 5-membered heteroaryl ring containing two, three, or four nitrogen members, wherein the 5-membered heteroaryl ring is optionally substituted with one R a member;
R b is H or C 1-4 akyl;
R c is H or C 1-4 haloalkyl;
R d is H or halo;
R e is selected from the group consisting of: H, halo, C 1-4 akyl, C 1-4 haloalkyl, OC 1-4 alkyl, and C 3-6 cycloalkyl;
R f is selected from the group consisting of: H, C 1-4 alkyl, CH 2 CH 2 OH, C 1-4 haloalkyl, cyclopropyl, phenyl, and phenyl substituted with CF 3 ;
R g is selected from the group consisting of: H, OC 1-4 alkyl and C 1-4 haloalkyl;
R i is H, halo, C 1-4 alkyl, C 1-4 haloalkyl, OH, OC 1-4 alkyl, OC 1-4 haloalkyl, C 3-6 cycloalkyl;
R j is selected from the group consisting of: H, halo, OCH 3 , OH, NH 2 , and NO 2 ;
R 3 is selected from the group consisting of:
(g) phenyl, wherein phenyl is independently substituted with one, two, or three members selected from the group consisting of: halo, C 1-4 alkyl, C 1-4 haloalkyl, and OC 1-4 alkyl;
(h) 5-(trifluoromethyl)-2-thienyl or 1-methylindol-2-yl; and
(i) cyclopropyl; and
R 4 is C 1-4 alkyl or C 3-4 cycloalkyl;
and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers of compounds of Formula (I);
(B) at least one pharmaceutically acceptable excipient.
61 - 62 . (canceled)
63 . A method of treating a subject suffering from or diagnosed with a disease, disorder, or condition mediated by MGL receptor activity, comprising administering to a subject in need of such treatment a therapeutically effective amount of at least one compound of Formula (I):
wherein
R 2 is selected from the group consisting of:
(a)
(b) 6-membered heteroaryl selected from the group consisting of: pyridazin-4-yl; pyrazin-2-yl;
pyrimidinyl; pyrimidinyl substituted with C 1-4 alkyl or OC 1-4 alkyl; and pyridinyl, wherein the pyridinyl is substituted with one or two substituents each independently selected from the group consisting of: halo, C 1-4 alkyl, OC 1-4 alkyl, OC 1-4 haloalkyl, C 3-6 cycloalkyl, NH 2 , CN, N(CH 3 ) 2 ,
(c) 5-membered heteroaryl selected from the group consisting of:
(d) 5,6-fused bicyclic heteroaryl or 6,5-fused bicyclic heteroaryl selected from the group consisting of:
(e) 6,6-fused bicyclic heteroaryl selected from the group consisting of:
and
(f)
wherein
R a is selected from the group consisting of: H, halo, C 1-4 alkyl, OC 1-4 alkyl, C 1-4 haloalkyl and OC 1-4 haloalkyl;
R a1 is selected from the group consisting of: C 1-4 alkyl, OC 1-4 alkyl, OC 1-4 haloalkyl, N(C═O)CH 3 , oxazol-2-yl, pyrimidin-2-yl, and 5-membered heteroaryl ring containing two, three, or four nitrogen members, wherein the 5-membered heteroaryl ring is optionally substituted with one R a member;
R b is H or C 1-4 akyl;
R c is H or C 1-4 haloalkyl;
R d is H or halo;
R e is selected from the group consisting of: H, halo, C 1-4 akyl, C 1-4 haloalkyl, OC 1-4 alkyl, and C 3-6 cycloalkyl;
R f is selected from the group consisting of: H, C 1-4 alkyl, CH 2 CH 2 OH, C 1-4 haloalkyl, cyclopropyl, phenyl, and phenyl substituted with CF 3 ;
R g is selected from the group consisting of: H, OC 1-4 alkyl and C 1-4 haloalkyl;
R i is H, halo, C 1-4 alkyl, C 1-4 haloalkyl, OH, OC 1-4 alkyl, OC 1-4 haloalkyl, C 3-6 cycloalkyl;
R j is selected from the group consisting of: H, halo, OCH 3 , OH, NH 2 , and NO 2 ;
R 3 is selected from the group consisting of:
(g) phenyl, wherein phenyl is independently substituted with one, two, or three members selected from the group consisting of: halo, C 1-4 alkyl, C 1-4 haloalkyl, and OC 1-4 alkyl;
(h) 5-(trifluoromethyl)-2-thienyl or 1-methylindol-2-yl; and
(i) cyclopropyl; and
R 4 is C 1-4 alkyl or C 3-4 cycloalkyl;
and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers thereof.
64 - 83 . (canceled)Cited by (0)
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