Substituted pyrazole compounds as indoleamine 2,3-dioxygenase inhibitors
Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme: (I). Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.
1. A compound of formula (I), or a pharmaceutically acceptable salt thereof:
wherein:
each of the dashed lines “ . . . ” is an optional bond;
m is 1; n is 1;
R a is selected from: (1) hydrogen and (2) C 1-6 alkyl;
Rb is hydrogen;
R c is selected from: (1) hydrogen, (2) halogen, and (3) C 1-6 alkyl;
R 1 and R 2 together with the nitrogen to which they are attached form a 4-6 membered heterocyclyl containing the one nitrogen to which they are attached and zero to two additional hetero atoms independently selected from N, S and O; wherein the heterocyclyl is optionally substituted with one to four substituents independently selected from:
(a) halogen,
(b) —OH,
(c) C 1-6 alkyl, optionally substituted with one to four substituents independently selected from (i) —OH, (ii) halogen and (iii) —C(O)—NHR e , wherein R e is selected from (i) hydrogen and (ii) C 1-6 alkyl,
(d) —O—C 1-6 alkyl, optionally substituted with one to four substituents independently selected from (i) —OH and (ii) halogen,
(e) —NHR f , wherein R f is selected from (i) hydrogen, (ii) C 1-6 alkyl and (iii) —C(O)—C 1-6 alkyl, and
(f) —C(O)—C 1-6 alkyl, optionally substituted with one to four substituents independently selected from (a) —OH and (b) halogen; and
R 3 is selected from (1) C 6-10 carbocyclyl and (2) heterocyclyl, wherein each of the carbocyclyl and heterocyclyl is optionally substituted with one to four substituents independently selected from:
(a) halogen,
(b) C 1-6 alkyl, optionally substituted with one to four halogens,
(c) —O—C 1-6 alkyl, optionally substituted with one to four halogens,
(d) —CN, and
(e) C 3-6 cycloalkyl, optionally substituted with C 1-6 alkyl.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R a is hydrogen.
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R c is selected from: (1) hydrogen, (2) fluoro, and (3) methyl.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 1 and R 2 together with the nitrogen to which they are attached form a 4-6 membered heterocyclyl containing the one nitrogen to which they are attached and zero to one additional hetero atoms independently selected from N and O; wherein the heterocyclyl is optionally substituted with one to three substituents independently selected from:
(a) halogen,
(b) —OH,
(c) C 1-4 alkyl, optionally substituted with one to three substituents independently selected from (i) —OH, (ii) halogen, and (iii) —C(O)—NH 2 ,
(d) —O—C 1-4 alkyl, optionally substituted with one to three substituents independently selected from (a) —OH and (b) fluoro,
(e) —NHR f , wherein R f is selected from (i) hydrogen and (ii) —C(O)—C 1-4 alkyl, and
(f) —C(O)—C 1-4 alkyl, optionally substituted with one to three substituents independently selected from (a) —OH and (b) halogen.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 1 and R 2 together with the nitrogen to which they are attached form a 4-6 membered heterocyclyl selected from azetidinyl, morpholinyl, piperidinyl, piperazinyl, and pyrrolidinyl; wherein the heterocyclyl is optionally substituted with one to three substituents independently selected from:
(a) halogen,
(b) —OH,
(c) methyl, optionally substituted with one to three substituents independently selected from (i) halogen and (ii) —C(O)—NH 2 ,
(d) —O—C 1-4 alkyl, optionally substituted with —OH,
(e) —NHR f , wherein R f is selected from (i) hydrogen and (ii) —C(O)—CH 3 , and
(f) —C(O)—C 1-4 alkyl, optionally substituted with —OH.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 3 is selected from:
(1) aryl,
(2) a phenyl fused to a C 4-5 cycloalkyl,
(3) C 3-6 cycloalkyl, and
(4) heterocyclyl;
wherein each of the aryl of (1) and the heterocyclyl of (4) is optionally substituted with one to four substituents independently selected from:
(a) halogen,
(b) C 1-4 alkyl, optionally substituted with one to three halogens,
(c) —O—C 1-4 alkyl, optionally substituted with one to three halogens,
(d) —CN, and
(e) C 3-6 cycloalkyl, optionally substituted with C 1-4 alkyl.
7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 3 is selected from:
(1) phenyl,
(2) naphthyl,
(3) bicyclo[4.2.0]octa-1,3,5-trienyl,
(4) 2,3-dihydro-1H-indenyl,
(5) C 5-6 cycloalkyl, and
(6) a heterocyclyl selected from benzo[b]thiophenyl, benzo[d][1,3]dioxolyl, 2,3-dihydrobenzofuranyl, pyridinyl, and quinolinyl;
wherein each of the phenyl of (1), naphthyl of (2), and heterocyclyl of (6) is optionally substituted with one to four substituents independently selected from:
(a) halogen,
(b) methyl, optionally substituted with one to three halogens,
(c) ethyl, optionally substituted with one to three halogens,
(d) —O-methyl, optionally substituted with one to three halogens,
(e) —O-ethyl, optionally substituted with one to three halogens,
(f) —CN, and
(g) cyclopropyl, optionally substituted with methyl or ethyl.
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, of formula (Ia):
wherein:
m is 1; n is 1;
R a is selected from: (1) hydrogen and (2) C 1-4 alkyl;
Rb is hydrogen;
R c is selected from: (1) hydrogen, (2) fluoro, and (3) methyl;
R 1 and R 2 together with the nitrogen to which they are attached form a 4-6 membered heterocyclyl containing the one nitrogen to which they are attached and zero to one additional hetero atoms independently selected from N and O; wherein the heterocyclyl is optionally substituted with one to three substituents independently selected from:
(a) halogen,
(b) —OH,
(c) C 1-4 alkyl, optionally substituted with one to three substituents independently selected from (i) —OH, (ii) halogen, and (iii) —C(O)—NH 2 ,
(d) —O—C 1-4 alkyl, optionally substituted with one to three substituents independently selected from (a) —OH and (b) fluoro,
(e) —NHR f , wherein R f is selected from (i) hydrogen and (ii) —C(O)—C 1-4 alkyl, and
(f) —C(O)—C 1-4 alkyl, optionally substituted with one to three substituents independently selected from (a) —OH and (b) halogen; and
R 3 is selected from:
(1) aryl,
(2) a phenyl fused to a C 4-5 cycloalkyl,
(3) C 3-6 cycloalkyl, and
(4) heterocyclyl;
wherein each of the aryl of (1) and the heterocyclyl of (4) is optionally substituted with one to four substituents independently selected from:
(a) halogen,
(b) C 1-4 alkyl, optionally substituted with one to three halogens,
(c) —O—C 1-4 alkyl, optionally substituted with one to three halogens,
(d) —CN, and
(e) C 3-6 cycloalkyl, optionally substituted with C 1-4 alkyl.
9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof:
wherein:
R a is hydrogen;
Rb is hydrogen;
R c is selected from: (1) hydrogen and (2) fluoro, and (3) methyl;
R 1 and R 2 together with the nitrogen to which they are attached form a 4-6 membered heterocyclyl selected from azetidinyl, morpholinyl, piperidinyl, piperazinyl, and pyrrolidinyl; wherein the heterocyclyl is optionally substituted with one to three substituents independently selected from:
(a) halogen,
(b) —OH,
(c) methyl, optionally substituted with one to three substituents independently selected from (i) halogen and (ii) —C(O)—NH 2 ,
(d) ethyl, optionally substituted with one to three halogens,
(e) —O—C 1-4 alkyl, optionally substituted with —OH,
(f) —NHR f , wherein R f is selected from (i) hydrogen and (ii) —C(O)—CH 3 , and
(g) —C(O)—C 1-4 alkyl, optionally substituted with —OH; and
R 3 is selected from:
(1) phenyl,
(2) naphthyl,
(3) bicyclo[4.2.0]octa-1,3,5-trienyl,
(4) 2,3-dihydro-1H-indenyl,
(5) C 5-6 cycloalkyl, and
(6) a heterocyclyl selected from benzo[b]thiophenyl, benzo[d][1,3]dioxolyl, 2,3-dihydrobenzofuranyl, pyridinyl, and quinolinyl;
wherein each of the phenyl of (1), naphthyl of (2), and heterocyclyl of (6) is optionally substituted with one to four substituents independently selected from: wherein each of the phenyl of (1), naphthyl of (2), and the heterocyclyl of (6) is optionally substituted with one to four substituents independently selected from:
(a) halogen,
(b) methyl, optionally substituted with one to three halogens,
(c) ethyl, optionally substituted with one to three halogens,
(d) —O-methyl, optionally substituted with one to three halogens,
(e) —O-ethyl, optionally substituted with one to three halogens,
(f) —CN, and
(g) cyclopropyl, optionally substituted with methyl or ethyl.
10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, of formula (Ib):
wherein:
m is 1;
R a is selected from: (1) hydrogen and (2) C 1-4 alkyl;
Rb is hydrogen;
R c is selected from: (1) hydrogen, (2) fluoro, and (3) methyl;
R 1 and R 2 together with the nitrogen to which they are attached form a 4-6 membered heterocyclyl containing the one nitrogen to which they are attached and zero to one additional hetero atoms independently selected from N and O; wherein the heterocyclyl is optionally substituted with one to three substituents independently selected from:
(a) halogen,
(b) —OH,
(c) C 1-4 alkyl, optionally substituted with one to three substituents independently selected from (i) —OH, (ii) halogen, and (iii) —C(O)—NH 2 ,
(d) —O—C 1-4 alkyl, optionally substituted with one to three substituents independently selected from (a) —OH and (b) fluoro,
(e) —NHR f , wherein R f is selected from (i) hydrogen and (ii) —C(O)—C 1-4 alkyl, and
(f) —C(O)—C 1-4 alkyl, optionally substituted with one to three substituents independently selected from (a) —OH and (b) halogen; and
R 3 is selected from:
(1) aryl,
(2) a phenyl fused to a C 4-5 cycloalkyl,
(3) C 3-6 cycloalkyl, and
(4) heterocyclyl;
wherein each of the aryl of (1) and heterocyclyl of (4) is optionally substituted with one to four substituents independently selected from:
(a) halogen,
(b) C 1-4 alkyl, optionally substituted with one to three halogens,
(c) —O—C 1-4 alkyl, optionally substituted with one to three halogens,
(d) —CN, and
(e) C 3-6 cycloalkyl, optionally substituted with C 1-4 alkyl.
11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof:
wherein:
m is 1;
R a is hydrogen;
each occurrence of R b is hydrogen;
R c is selected from: (1) hydrogen and (2) fluoro;
R 1 and R 2 together with the nitrogen to which they are attached form a 4-6 membered heterocyclyl selected from azetidinyl, morpholinyl, piperidinyl, piperazinyl, and pyrrolidinyl; wherein the heterocyclyl is optionally substituted with one to three substituents independently selected from:
(a) halogen,
(b) —OH,
(c) methyl, optionally substituted with one to three substituents independently selected from (i) —OH and (ii) —C(O)—NH 2 ,
(d) —O—C 1-4 alkyl, optionally substituted with —OH,
(e) —NHR f , wherein R f is selected from (i) hydrogen and (ii) —C(O)—CH 3 , and
(f) —C(O)—C 1-4 alkyl, optionally substituted with —OH; and
R 3 is phenyl, optionally substituted with one to three substituents independently selected from:
(a) halogen, and
(b) methyl, optionally substituted with one to three halogens.
12. The compound of claim 1 selected from the group consisting of:
2-((3bR,4aR)-3-(4-(fluoromethyl)-4-hydroxypiperidine-1-carbonyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)-1-(4-(2-methyl-3-(trifluoromethyl) phenyl)piperidin-1-yl)ethanone,
2-((3bR,4aR)-3-(4-hydroxypiperidine-1-carbonyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4] cyclopenta[1,2-c]pyrazol-1-yl)-1-(4-(2-methyl-3-(trifluoromethyl)phenyl)piperidin-1-yl) ethanone,
2-hydroxy-1-(4-((3bR,4aR)-1-(2-(4-(2-methyl-3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazole-3-carbonyl)piperazin-1-yl)ethanone,
2-((3bR,4aR)-3-((S)-2-(hydroxymethyl)morpholine-4-carbonyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)-1-(4-(2-methyl-3-(trifluoromethyl)phenyl) piperidin-1-yl)ethanone,
2-((3bR,4aR)-3-((R)-2-(hydroxymethyl)morpholine-4-carbonyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)-1-(4-(2-methyl-3-(trifluoromethyl)phenyl) piperidin-1-yl)ethanone,
2-(4-((3bR,4aR)-1-(2-(4-(2-methyl-3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazole-3-carbonyl)piperazin-1-yl)acetamide,
2-(3-((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)-1-(4-(2,3-dimethylphenyl)-4-fluoropiperidin-1-yl)ethanone,
1-(4-(2,3-dimethylphenyl)-4-fluoropiperidin-1-yl)-2-((3bR,4aR)-3-(4-(2-hydroxyethoxy)piperidine-1-carbonyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)ethanone,
1-(4-(2,3-dimethylphenyl)-4-fluoropiperidin-1-yl)-2-(3-(4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(2,3-dimethylphenyl)-4-fluoropiperidin-1-yl)-2-((3bR,4aR)-3-(4-hydroxypiperidine-1-carbonyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)ethanone,
1-(4-(2,3-dimethylphenyl)-4-fluoropiperidin-1-yl)-2-((3bR,4aR)-3-(4-(2-hydroxyacetyl)piperazine-1-carbonyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa [3,4]cyclopenta[1,2-c]pyrazol-1-yl)ethanone,
N-(1-((3bR,4aR)-1-(2-(4-(2,3-dimethylphenyl)-4-fluoropiperidin-1-yl)-2-oxoethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazole-3-carbonyl)piperidin-4-yl)acetamide,
2-((3bR,4aR)-3-(4-aminopiperidine-1-carbonyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4] cyclopenta[1,2-c]pyrazol-1-yl)-1-(4-(2,3-dimethylphenyl)-4-fluoropiperidin-1-yl)ethanone,
1-(4-(2,3-dimethylphenyl)-3,3-difluoropiperidin-1-yl)-2-(3-(4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)piperidin-1-yl)-2-(3-(4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
(S)-1-(4-(2,3-dimethylphenyl)piperazin-1-yl)-2-(3-(4-(2-hydroxyacetyl)-3-methylpiperazine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(3-chloro-2-methylphenyl)piperidin-1-yl)-2-((3bR,4aR)-3-(4-(2-hydroxyacetyl)piperazine-1-carbonyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)ethanone,
1-[4-(2,3-dimethylphenyl)piperidin-1-yl]-2-{(3bR,4aR)-3-[4-(hydroxyacetyl)piperazine-1-carbonyl]-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl}ethan-1-one,
1-[4-(2,3-dimethylphenyl)piperidin-1-yl]-2-{(3bR,4aR)-3-[(3R,4R)-4-hydroxy-3-methylpiperidine-1-carbonyl]-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl}ethan-1-one,
1-[4-(2,3-dimethylphenyl)piperidin-1-yl]-2-{(3bR,4aR)-3-[(3R,4S)-4-hydroxy-3-methylpiperidine-1-carbonyl]-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl}ethan-1-one,
1-[4-(2,3-dimethylphenyl)piperidin-1-yl]-2-{(3bR,4aR)-3-[(3S,4S)-4-hydroxy-3-methylpiperidine-1-carbonyl]-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl}ethan-1-one,
1-[4-(2,3-dimethylphenyl)piperidin-1-yl]-2-{(3bR,4aR)-3-[(3S,4R)-4-hydroxy-3-methylpiperidine-1-carbonyl]-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl}ethan-1-one,
1-[4-(2,3-dimethylphenyl)piperidin-1-yl]-2-{(3bR,4aR)-3-[(3S,4S)-3-fluoro-4-hydroxypiperidine-1-carbonyl]-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl}ethan-1-one,
1-[4-(2,3-dimethylphenyl)piperidin-1-yl]-2-{(3bR,4aR)-3-[(3R,4R)-3-fluoro-4-hydroxypiperidine-1-carbonyl]-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl}ethan-1-one,
1-[4-(2,3-dimethylphenyl)piperidin-1-yl]-2-{(3bR,4aR)-3-[(3R,4S)-3-fluoro-4-hydroxypiperidine-1-carbonyl]-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl}ethan-1-one,
1-[4-(2,3-dimethylphenyl)piperidin-1-yl]-2-{(3bS,4aS)-3-[(3S,4R)-3-fluoro-4-hydroxypiperidine-1-carbonyl]-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl}ethan-1-one,
1-[4-(2,3-dimethylphenyl)piperidin-1-yl]-2-{(3bS,4aS)-3-[4-(hydroxyacetyl)piperazine-1-carbonyl]-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl}ethan-1-one,
1-[4-(2,3-dimethylphenyl)piperidin-1-yl]-2-{(3bS,4aS)-3-[(3R,4S)-3-fluoro-4-hydroxypiperidine-1-carbonyl]-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl}ethan-1-one,
1-(4-cyclohexylpiperidin-1-yl)-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(2,3-dimethylphenyl)-1-piperidyl]-2-[3-[4-(fluoromethyl)-4-hydroxy-piperidine-1-carbonyl]-5,6-dihydro-4H-cyclopenta[c]pyrazol-1-yl]ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-((3S,4S)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(4-(2-hydroxyethoxy)piperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(4-hydroxypiperidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-((3S,4R)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(4-(fluoromethyl)-4-hydroxypiperidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-((3S,4S)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(4-(2-hydroxyethoxy)piperidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-((3R,4R)-4-hydroxy-3-methylpiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethan-1-one,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(4-hydroxy-4-methylpiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethan-1-one,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethan-1-one,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(4-(2-hydroxyacetyl)piperazine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)ethanone,
(S)-1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(2-(hydroxymethyl)morpholine-4-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-((3R,4S)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-((3R,4R)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-5,6dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(morpholine-4-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethan-1-one,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(4-(2-hydroxyacetyl)piperazine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
(S)-1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(3-hydroxypyrrolidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethan-1-one,
(S)-1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(3-hydroxy-3-methylpyrrolidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethan-1-one,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(3-hydroxy-3-methylazetidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethan-1-one,
(R)-1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-(3-hydroxypyrrolidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethan-1-one,
1-(4-(4-fluoro-2-methylphenyl)piperidin-1-yl)-2-(3-((3S,4S)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(4-fluoro-2-methylphenyl)piperidin-1-yl)-2-(3-(4-(fluoromethyl)-4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(4-fluoro-2-methylphenyl)piperidin-1-yl)-2-(3-((3R,4R)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(4-fluoro-2-methylphenyl)piperidin-1-yl)-2-(3-((3S,4R)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(4-fluoro-2-methylphenyl)piperidin-1-yl)-2-(3-((3R,4S)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(4-fluoro-2-methylphenyl)piperidin-1-yl)-2-(3-(4-(2-hydroxyacetyl)piperazine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
(S)-1-(4-(4-fluoro-2-methylphenyl)piperidin-1-yl)-2-(3-(2-(hydroxymethyl)morpholine-4-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-((3R,4S)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-((3S,4R)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
1-(4-(2,3-dimethylphenyl)piperidin-1-yl)-2-(3-((3R,4S or 3S, 4R)-3-fluoro-4-hydroxypiperidine-1-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)ethanone,
2-(3-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)-1-(4-(o-tolyl)piperidin-1-yl)ethan-1-one,
2-[3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydro-4H-cyclopenta[c]pyrazol-1-yl]-1-(4-fluoro-4-phenyl-1-piperidyl)ethanone,
2-(3-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)-1-(4-(2,3-dimethylphenyl)piperidin-1-yl)ethanone,
2-(3-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)-1-(4-(m-tolyl)piperidin-1-yl)ethanone,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-(4-methyl-4-phenylpiperidin-1-yl)ethan-1-one,
1-[4-(3,5-difluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(4-fluorophenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(naphthalen-1-yl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-(4-phenylpiperidin-1-yl)ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[2-(trifluoromethyl)phenyl]piperidin-1-yl}ethan-1-one,
1-(3,3-difluoro-4-phenylpiperidin-1-yl)-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{3-[2-(trifluoromethyl)phenyl]pyrrolidin-1-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-(4-phenylazepan-1-yl)ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2-methoxyphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(naphthalen-2-yl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[3-(3-fluoro-2-methylphenyl)piperidin-1-yl]ethan-1-one,
1-[3-(2-chlorophenyl)pyrrolidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[(3R,4R)-3-methyl-4-phenylpiperidin-1-yl]ethan-1-one,
2-(3-(cis-2,6-dimethylmorpholine-4-carbonyl)-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl)-1-(4-(3,4-dimethylpyridin-2-yl)piperidin-1-yl)ethan-1-one,
1-[4-(4-chloro-3-methylphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(3-chloro-2-methylphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[2-methyl-3-(trifluoromethyl)phenyl]piperidin-1-yl}ethan-1-one,
1-[4-(benzothiophen-7-yl)-1-piperidyl]-2-[3-[(2S,6R)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydro-4H-cyclopenta[c]pyrazol-2-ium-1-yl]ethanone; 2,2,2-trifluoroacetate,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(5-fluoronaphthalen-1-yl)piperidin-1-yl]ethan-1-one,
1-[4-(2,3-dihydro-1H-inden-4-yl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(2,3-dichlorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(1-benzothiophen-4-yl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(3,4-dimethylphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(3-fluoro-5-methylphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(3-fluoro-4-methylphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(4-fluoro-2-methylphenyl)piperidin-1-yl]ethan-1-one,
1-[4-(2,3-dihydro-1-benzofuran-5-yl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(4-fluoro-3-methylphenyl)piperidin-1-yl]ethan-1-one,
1-[4-(3-chloro-5-fluoro-4-methoxyphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(3-ethylphenyl)piperidin-1-yl]ethan-1-one,
1-[4-(2-chloro-3-fluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(5-fluoro-2-methylphenyl)piperidin-1-yl]ethan-1-one,
1-[4-(3-chloro-5-fluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(3-chloro-4-fluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(4-chloro-3,5-difluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(4-methoxy-3,5-dimethylphenyl)piperidin-1-yl]ethan-1-one,
1-[4-(3-cyclopropylphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[2-fluoro-3-(trifluoromethyl)phenyl]piperidin-1-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2,4-dimethylphenyl)piperidin-1-yl]ethan-1-one,
1-[4-(4-chloro-2-methylphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(3-chlorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(3-methoxyphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2-ethylphenyl)piperidin-1-yl]ethan-1-one,
1-[4-(3,5-difluoro-2-methoxyphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(3-chloro-4-methylphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(4-chloro-3-fluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(2-cyclopropylphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(4-chlorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(3-fluoro-2-methoxyphenyl)piperidin-1-yl]ethan-1-one,
1-[4-(4-chloro-3,5-dimethylphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2,3,5-trifluorophenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2-fluoro-5-methylphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[4-methyl-3-(trifluoromethyl)phenyl]piperidin-1-yl}ethan-1-one,
1-[4-(2,3-difluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(3,5-dichloro-2-methylphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(3,4-dichlorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(2-chloro-4-fluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[3-(1-methylcyclopropyl)phenyl]piperidin-1-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(3,4,5-trifluorophenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(4-methylphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2,3,4-trifluorophenyl)piperidin-1-yl]ethan-1-one,
3-[1-({3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}acetyl)piperidin-4-yl]-2-methylbenzonitrile,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(3-fluorophenyl)piperidin-1-yl]ethan-1-one,
1-[4-(4-cyclopropylphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(2-chloro-3,4,5-trifluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-{4-[3-(difluoromethyl)-4-fluorophenyl]piperidin-1-yl}-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(3,5-difluoro-4-methoxyphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(4-chloro-2-fluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2,4,5-trimethylphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2-fluoro-4-methoxyphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(4-methoxy-2,3-dimethylphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(4-fluoro-3,5-dimethylphenyl)piperidin-1-yl]ethan-1-one,
1-{4-[4-(difluoromethyl)-3-fluorophenyl]piperidin-1-yl}-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[3-fluoro-5-(trifluoromethyl)phenyl]piperidin-1-yl}ethan-1-one,
1-{4-[4-(difluoromethyl)-2-fluorophenyl]piperidin-1-yl}-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(˜2˜H_5_)phenylpiperidin-1-yl]ethan-1-one,
1-[4-(3,4-difluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2-fluorophenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(4-ethylphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[2-fluoro-4-(trifluoromethyl)phenyl]piperidin-1-yl}ethan-1-one,
1-[4-(3-chloro-5-methylphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2,4,5-trifluorophenyl)piperidin-1-yl]ethan-1-one,
1-[4-(2,5-difluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[4-fluoro-3-(trifluoromethyl)phenyl]piperidin-1-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2,3,6-trifluorophenyl)piperidin-1-yl]ethan-1-one,
1-[4-(2,2-difluoro-2H-1,3-benzodioxol-4-yl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(2-chloro-4,5-difluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(3,5-dimethylphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2-fluoro-5-methoxyphenyl)piperidin-1-yl]ethan-1-one,
1-[4-(2-chlorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(2-fluoro-6-methylphenyl)piperidin-1-yl]ethan-1-one,
1-{4-[3-(1,1-difluoroethyl)phenyl]piperidin-1-yl}-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[3-(trifluoromethoxy)phenyl]piperidin-1-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[3-fluoro-4-(trifluoromethyl)phenyl]piperidin-1-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[2-methyl-4-(trifluoromethyl)phenyl]piperidin-1-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[2-(trifluoromethoxy)phenyl]piperidin-1-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[3-(2,2,2-trifluoroethyl)phenyl]piperidin-1-yl}ethan-1-one,
1-[4-(2,4-difluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(5-chloro-2-fluorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(3,5-dichlorophenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-{4-[4-(propan-2-yl)phenyl]piperidin-1-yl}ethan-1-one,
1-{4-[3-chloro-4-(trifluoromethyl)phenyl]piperidin-1-yl}-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
1-[4-(5-chloro-2-methoxyphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(isoquinolin-5-yl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(4-fluoro-2,3-dimethylphenyl)piperidin-1-yl]ethan-1-one,
2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}-1-[4-(3-fluoro-2-methylphenyl)piperidin-1-yl]ethan-1-one, and
1-[4-(3,4-difluoro-2-methylphenyl)piperidin-1-yl]-2-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5,6-dihydrocyclopenta[c]pyrazol-1(4H)-yl}ethan-1-one;
or a pharmaceutically acceptable salt thereof.
13. A composition which comprises an inert carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.