Hexahydrocyclopentyl[
The present invention is directed to hexahydrocyclopentylf]imidazole carboxamides and derivatives thereof as selective glucocorticoid receptor ligands useful for treating a variety of autoimmune and inflammatory diseases or conditions. Pharmaceutical compositions and methods of use are also included.
1. A compound of Formula I
or a pharmaceutically acceptable salt thereof, wherein
R 1 is selected from the group consisting of:
(a) C 1-8 alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxy,
(3) oxo,
(4) —CF 3 ,
(5) —OCH 3 ,
(6) —CN,
(7) pyridine,
(8) —O—S(O) 2 —CF 3 , and
(9) —O—S(O) 2 —C 1-2 alkyl-CF 3 ,
(b) C 2-6 alkenyl, optionally mono-, di- or tri substituted with fluoro,
(c) —C 3-6 cycloalkyl,
(d) —C 1-2 alkylC 3-6 cycloalkyl,
(e) heterocycle,
(f) —C 1-2 alkylheterocycle,
(g) aryl selected from phenyl or naphthyl,
(h) —C 1-4 alkylaryl,
(i) —C 1-4 alkyl-O-aryl,
(j) —C 2-4 alkenylaryl,
(k) heteroaryl,
(l) —C 1-2 alkylheteroaryl,
(m) —C1-4alkyl-O—C1-6alkyl, optionally substituted with hydroxy, or —O—S(O) 2 —C 1-2 alkyl-CF 3 ,
(o) —CH 2 —C(O)C 1-4 alkyl,
(p) —CH 2 —C(O)heterocycle,
wherein the alkyl of choice (h) is optionally substituted with aryl, C 1-4 alkyl, and
wherein the heteroaryl, aryl, heterocycle and cycloalkyl of choices (c), (d), (e), (f), (g), (h), (i), (j), (k), (l), and (p) are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(1) hydroxyl,
(2) halo,
(3) —CN,
(4) —CF 3 ,
(5) —C 1-6 alkyl,
(6) -fluoroC 1-6 alkyl,
(7) —OC 1-6 alkyl,
(8) —O-fluoroC 1-4 alkyl,
(9) heteroaryl selected from pyrazole, thiophene, imidazole, and oxazole, optionally substituted with 1, 2 or 3 substitutents independently selected from methyl, and halo,
(10) —NH—OCH 3 ,
(11) phenyl,
(12) —O-phenyl,
(13) pyridine,
(14) —O-pyridine,
(15) —NH—C(O)—NH—CH 3 ,
(16) —NH—C(O)—C 1-4 alkyl,
(17) —NH—C(O)—C 3-6 cycloalkyl,
(18) —C 1-3 alkyl-C(O)—OH,
(19) —C 1-3 alkyl-C(O)—O—CH 3 ,
(20) —C(O)—NH 2 ,
(21) —C(O)—C 1-4 alkyl-NH 2 ,
(22) —C(O)—NH—C 3-6 cycloalkyl,
(23) —C(O)—OH,
(24) —C(O)—O—C 1-4 alkyl,
(25) —C 1-2 alkyl-heterocycle,
(26) —C 2-4 alkenyl-C(O)-phenyl,
(27) —O—S(O) 2 —C 1-2 alkyl-CF 3 ,
(28) —S(O) 2 —NH 2 , and
(29) —S(O) 2 -phenyl;
R 2 is selected from the group consisting of:
(a) H,
(b) C 1-8 alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxyl,
(3) oxo,
(4) —CN,
(5) pyridine,
(6) —O—S(O) 2 —CF 3 , and
(7) —O—S(O) 2 —C 1-2 alkyl-CF 3 ,
(c) C 2-6 alkenyl, optionally mono-, di- or tri substituted with fluoro,
(d) —C 1-2 alkylC 3-6 cycloalkyl,
(e) heterocycle,
(f) —C 1-2 alkylheterocycle,
(g) aryl selected from phenyl or naphthyl,
(h) —C 1-2 alkylaryl,
(i) —C 2-4 alkenylaryl,
(j) heteroaryl,
(k) —C 1-2 alkylheteroaryl,
(l) —Oheteroaryl,
(m) —OC 1-6 alkyl optionally mono-, di- or tri substituted with fluoro,
(n) —C1-4alkyl-O—C1-6alkyl, optionally substituted with hydroxy, or —O—S(O) 2 —C 1-2 alkyl-CF 3 ,
(o) —OC 3-6 cycloalkyl,
(p)—Oaryl,
wherein the heteroaryl, aryl, heterocycle and cycloalkyl of choices (d), (e) (f), (g), (h), (i), (j), (k), (l), (o) and (p) are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(1) hydroxyl,
(2) halo,
(3) —CN,
(4) —CF 3 ,
(5) —C 1-6 alkyl,
(6) —C 1-6 alkyl,
(7) —O—CH 2 CF 3 ,
(8) heteroaryl selected from pyrazole, thiophene, imidazole, and oxazole, optionally substituted with 1, 2 or 3 substitutents independently selected from methyl, and halo,
(9) —NH—OCH 3 ,
(10) phenyl,
(11) —O-phenyl,
(12) pyridine,
(13) —O-pyridine,
(14) —NH—C(O)—NH—CH 3 ,
(15) —NH—C(O)—C 1-4 alkyl,
(16) —NH—C(O)—C 3-6 cycloalkyl,
(17) —C 1-3 alkyl-C(O)—OH,
(18) —C 1-3 alkyl-C(O)—O—CH 3 ,
(19) —C(O)—NH 2 ,
(20) —C(O)—C 1-4 alkyl-NH 2 ,
(21) —C(O)—NH—C 3-6 cycloalkyl,
(22) —C(O)—OH,
(23) —C(O)—O—C 1-4 alkyl,
(24) —C 1-2 alkyl-heterocycle,
(25) —C 2-4 alkenyl-C(O)-phenyl, and
(26) —O—S(O) 2 —C 1-2 alkyl-CF 3 , or
R 1 and R 2 are joined so that together with the nitrogen atom to which they are attached there is formed an unsaturated ring of 4, 5, 6 or 7 atoms, said ring optionally containing 1 or 2 additional heteroatoms selected from N and O, and said ring being optionally mono- or di-substituted with substitutents independently selected from
(1)oxo,
(2) hydroxyl,
(3) C 1-4 alkyl,
(4) —OC 1-4 alkyl,
(5) —C 1-4 phenyl,
(6) —Ophenyl
(7) —C(O)—NH 2 ,
(8) —CH 2 phenyl,
(9) —CH 2 —O-phenyl,
(10) fluoroC 1-4 alkyl,
(11) —SO 2 phenyl,
Wherein the phenyl of choices (5) and (6) are optionally mono or di-substituted with substituents independently selected from halo, fluoroC 1-3 alkyl,
R 4
(a) H, or
(b) fluoro.
2. The compound according to claim 1 wherein
R 1 is selected from the group consisting of:
(a) C 1-8 alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxy,
(3) oxo,
(4) —CF 3 ,
(5) —OCH 3 ,
(6) —CN,
(7) pyridine,
(8) —O—S(O) 2 —CF 3 , and
(9) —O—S(O) 2 —C 1-2 alkyl-CF 3 ,
(b) —C 1-2 alkylC 3-6 cycloalkyl,
(c) —C 1-2 alkylheterocycle,
(d) —C 1-4 alkylaryl,
(e)—C 1-4 alkyl-O-aryl,
(f) —C 2-4 alkenylaryl,
(g) —C 1-2 alkylheteroaryl,
(h) —C1-4alkyl-O—C1-6alkyl, optionally substituted with hydroxy, or —O—S(O) 2 —C 1-2 alkyl-CF 3 ,
(i) —CH 2 —C(O)C 1-4 alkyl,
(j) —CH 2 —C(O)heterocycle,
wherein the alkyl of choice (d) is optionally substituted with aryl, C 1-4 alkyl, and
wherein the heteroaryl, aryl, heterocycle and cycloalkyl of choices (b), (c), (d), (e), (f), (g) and (j), are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(1) hydroxyl,
(2) halo,
(3) —CN,
(4) —CF 3 ,
(5) —C 1-6 alkyl,
(6) -fluoroC 1-6 alkyl,
(7) —OC 1-6 alkyl,
(8) —O-fluoroC 1-4 alkyl,
(9) heteroaryl selected from pyrazole, thiophene, imidazole, and oxazole, optionally substituted with 1, 2 or 3 substitutents independently selected from methyl, and halo,
(10) —NH—OCH 3 ,
(11) phenyl,
(12) —O-phenyl,
(13) pyridine,
(14) —O-pyridine,
(15) —NH—C(O)—NH—CH 3 ,
(16) —NH—C(O)—C 1-4 alkyl,
(17) —NH—C(O)—C 3-6 cycloalkyl,
(18) —C 1-3 alkyl-C(O)—OH,
(19) —C 1-3 alkyl-C(O)—O—CH 3 ,
(20) —C(O)—NH 2 ,
(21) —C(O)—C 1-4 alkyl-NH 2 ,
(22) —C(O)—NH—C 3-6 cycloalkyl,
(23) —C(O)—OH,
(24) —C(O)—O—C 1-4 alkyl, and
(25) —C 1-2 alkyl-heterocycle.
3. The compound according to claim 2 wherein
R 1 is selected from the group consisting of
(a) C 1-8 alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxy,
(3) oxo,
(4) —CF 3 ,
(5) —OCH 3 ,
(6) —CN,
(7) pyridine,
(8) —O—S(O) 2 —CF 3 , and
(9) —O—S(O) 2 —C 1-2 alkyl-CF 3 ,
(b) —C 1-2 alkylC 3-6 cycloalkyl,
(c) —C 1-2 alkylheterocycle,
(d)
(e) —C 1-4 alkyl-O-aryl,
(f) —C 2-4 alkenylaryl,
(g) —C 1-2 alkylheteroaryl, and
wherein the alkyl of choice (d) is optionally substituted with aryl, C 1-4 alkyl, and
wherein the heteroaryl, aryl, heterocycle and cycloalkyl of choices (b), (c), (d), (e) and (f), are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(2) halo,
(3) —CN,
(4) —-CF 3 ,
(5) —C 1-6 alkyl,
(6) -fluoroC 1-6 alkyl,
(7) —OC 1-6 alkyl, and
(8) —O-fluoroC 1-4 alkyl.
4. The compound according to claim 3 wherein R 1 is selected from the group consisting of:
(a) C 1-8 alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxy,
(3) oxo,
(4) —CF 3 , and
(5) —OCH 3 ,
(b) —C 1-2 alkylC 3-6 cycloalkyl,
(c) —C 1-2 alkylheterocycle,
(d)
(e) —C 1-2 alkylheteroaryl, and
wherein the alkyl of choice (d) is optionally substituted with aryl, C 1-4 alkyl, and
wherein the heteroaryl, acyl, heterocycle and cycloalkyl of choices (b), (c), (d) and (e), are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(1) halo,
(2) —CN,
(3) —CF 3 ,
(4) —C 1-6 alkyl,
(5) -fluoroC 1-6 alkyl,
(6) —OC 1-6 alkyl, and
(7) —O-fluoroC 1-4 alkyl.
5. The compound according to claim 1 wherein
R 2 is selected from the group consisting of:
(a) hydrogen,
(b) C 1-8 alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxy,
(3) oxo,
(4) —CF 3 ,
(5) —OCH 3 ,
(6) —CN,
(7) pyridine,
(8) —O—S(O) 2 —CF 3 , and
(9) —O—S(O) 2 —C 1-2 alkyl-CF 3 ,
(c) —C 1-2 alkylC 3-6 cycloalkyl,
(d) —C 1-2 alkylheterocycle,
(e) —C 1-4 alkylaryl,
(f) —C 1-4 alkyl-O-aryl,
(g) —C 2-4 alkenylaryl,
(h) —C 1-2 alkylheteroaryl,
(i) —C 1-4 alkyl-O—C 1-6 alkyl, optionally substituted with hydroxy, or —O—S(O) 2 —C 1-2 alkyl-CF 3 ,
(j) —CH 2 —C(O)C 1-4 alkyl,
(k) —CH 2 —C(O)heterocycle,
wherein the alkyl of choice (e) is optionally substituted with aryl, C 1-4 alkyl, and
wherein the heteroaryl, aryl, heterocycle and cycloalkyl of choices (c), (d), (e), (f), (g) (h) and (k), are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(1) hydroxyl,
(2) halo,
(3) —CN,
(4) —CF 3 ,
(5) —C 1-6 alkyl,
(6) -fluoroC 1-6 alkyl,
(7) —OC 1-6 alkyl,
(8) —O-fluoroC 1-4 alkyl,
(9) heteroaryl selected from pyrazole, thiophene, imidazole, and oxazole, optionally substituted with 1, 2 or 3 substitutents independently selected from methyl, and halo,
(10) —NH—OCH 3 ,
(11) phenyl,
(12) —O-phenyl,
(13) pyridine,
(14) —O-pyridine,
(15) —NH—C(O)—NH—CH 3 ,
(16) —NH—C(O)—C 1-4 alkyl,
(17) —NH—C(O)—C 3-6 cycloalkyl,
(18) —C 1-3 alkyl-C(O)—OH,
(19) —C 1-3 alkyl-C(O)—O—CH 3 ,
(20) —C(O)—NH 2 ,
(21) —C(O)—C 1-4 alkyl-N142,
(22) —C(O)—NH—C 3-6 cycloalkyl,
(23) —C(O)—OH,
(24) —C(O)—O—C 1-4 alkyl, and
(25) —C 1-2 alkyl-heterocycle.
6. The compound according to claim 5 wherein
R 2 is selected from the group consisting of
(a) hydrogen,
(b) C 1-8 -alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxy,
(3) oxo,
(4) —CF 3 ,
(5) —OCH 3 ,
(6) —CN,
(7) pyridine,
(8) —O—S(O) 2 —CF 3 , and
(9) —O—S(O) 2 —C 1-2 alkyl-CF 3 ,
(c) —C 1-2 alkylC 3-6 cycloalkyl,
(d) —C 1-2 alkylheterocycle,
(e) —C 1-4 alkylaryl,
(f) —C 1-4 alkyl-O-aryl,
(g) —C 2-4 alkenylaryl,
(h) —C 1-2 alkylheteroaryl, and
wherein the alkyl of choice (e) is optionally substituted with aryl, C 1-4 alkyl, and
wherein the heteroaryl, aryl, heterocycle and cycloalkyl of choices (c), (d), (e), (f), (g) and (h), are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(1) halo,
(2) —CN,
(3) —CF 3 ,
(4) —C 1-6 alkyl,
(5) -fluoroC 1-6 alkyl,
(6) —OC 1-6 alkyl, and
(7) —O-fluoroC 1-4 alkyl.
7. The compound according to claim 6 wherein
R 2 is selected from the group consisting of:
(a) hydrogen,
(b) C 1-8 alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxy,
(3) oxo,
(4) —CF 3 , and
(5) —OCH 3 ,
(c) —C 1-2 alkylC 3-6 cycloalkyl,
(d) —C 1-2 alkylheterocycle,
(e) —C 1-4 alkylaryl,
(f) —C 1-2 alkylheteroaryl, and
wherein the alkyl of choice (e) is optionally substituted with aryl, C 1-4 alkyl, and
wherein the heteroaryl, aryl, heterocycle and cycloalkyl of choices (c), (d), (e) and (f), are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(1) halo,
(2) —CN,
(3) —CF 3 ,
(4) —C 1-6 alkyl,
(5)-fluoroC 1-6 alkyl,
(6) —OC 1-6 alkyl, and
(7) —O-fluoroC 1-4 alkyl.
8. The compound of claim 1 wherein
R 4 is fluoro.
9. The compound according to claim 1 wherein:
R 1 is selected from the group consisting of:
(a) C 1-8 alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxy,
(3) oxo,
(4) —CF 3 , and
(5) —OCH 3 ,
(b) —C 1-2 alkylC 3-6 cycloalkyl,
(c) —C 1-2 alkylheterocycle,
(d) —C 1-4 alkylaryl,
(e) —C 1-2 alkylheteroaryl, and
wherein the alkyl of choice (d) is optionally substituted with aryl, C 1-4 alkyl, and
wherein the heteroaryl, aryl, heterocycle and cycloalkyl of choices (b), (c), (d) and (e), are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(1) halo,
(2) —CN,
(3) —CF 3 ,
(4) —C 1-6 alkyl,
(5) -fluoroC 1-6 alkyl,
(6) —OC 1-6 alkyl, and
(7) —O-fluoroC 1-4 alkyl.
R 2 is selected from the group consisting of:
(a) hydrogen,
(b) C 1-8 alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxy,
(3) oxo,
(4) —CF 3 , and
(5) —OCH 3 ,
(c) —C 1-2 alkylC 3-6 cycloalkyl,
(d) —C 1-2 alkylheterocycle,
(e) —C 1-4 alkylaryl,
(f) —C 1-2 alkylheteroaryl, and
wherein the alkyl of choice (e) is optionally substituted with aryl, C 1-4 alkyl, and
wherein the heteroaryl, aryl, heterocycle and cycloalkyl of choices (c), (d), (e) and (f), are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(1) halo,
(2) —CN,
(3) —CF 3 ,
(4) —C 1-6 alkyl,
(5) -fluoroC 1-6 alkyl,
(6) —OC 1-6 alkyl, and
(7) —O-fluoroC 1-4 alkyl; and
R 4 is fluoro.
10. The compound according to claim 1 selected from the following group:
Ex.
NAME
1
(4αR,5S)-1-(4-fluorophenyL)-4α-methyl-N,N-dipropyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
2
(4αR,5S)-N-(1,2-diphenylethyl)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
3
(4αR,5S)-N-(2,4-dichlorobenzyl)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
4
(4αR,5S)-N-ethyl-1-(4-fluorophenyl)-4α-methyl-N-propyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
5
(4αR,5S)-N-(cyclopropylmethyl)-1-(4-fluorophenyl)-4α-methyl-N-propyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
6
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-N-phenyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
7
(4αR,5S)-N-(cyclopropylmethyl)-N-(2,4-dichilorobenzyl)-1-(4-fluorophenyl)-
4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
8
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-N,N-bis(3-methylbutyl)-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
9
(4αR,5S)-N,N-dibutyl-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
10
(4αR,5S)-1-(4-fluorophenyl)-N,N-bis(2-hydroxypropyl)-4α-methyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
11
(4αR,5S)-1-(4-fluorophenyl)-N,N-diisobutyl-4α-methyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
12
(4αR,5S)-N-butyl-N-ethyl-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
13
(4αR,5S)-N,N-bis(2-cyanoethyl)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
14
(4αR,5S)-N-(2-cyanoethyl)-N-cyclopropyl-1-(4-fluorophenyl)-4α-methyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
15
1-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazol-5-yl]carbonyl}azepan-4-one
16
(4αR,5S)-N-(sec-butyl)-1-(4-fluorophenyl)-4α-methyl-N-propyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
17
(4αR,5S)-5-[(2,6-dimethylmorpholin-4-yl)carbonyl]-1-(4-fluorophenyl)-4α-
methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole
18
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-5-{[2-(2-phenylethyl)piperidin-1-
yl]carbonyl}-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole
19
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-5-{[2-(2-phenylethyl)pyrrolidin-1-
yl]carbonyl}-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole
20
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-5-{[3-(2-phenylethyl)piperidin-1-
yl]carbonyl}-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole
21
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-5-({3-[3-
(trifluoromethyl)benzyl]piperidin-1-yl}carbonyl)-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole
22
(4αR,5S)-5-[(2-benzylpiperidin-1-yl)carbonyl]-1-(4-fluorophenyl)-4α-methyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole
23
(4αR,5S)-N-[2-(aminosulfonyl)phenyl]-1-(4-fluorophenyl)-4α-methyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
24
(4αR,5S)-N-[2-(ethylamino)-2-oxoethyl]-1-(4-fluorophenyl)-4α-methyl-N-(2-
phenylethyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
25
(4αR,5S)-N-(2-fluorobenzyl)-1-(4-fluorophenyl)-N-(2-hydroxyethy})-4α-
methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
26
(4αR,5S)-N-butyl-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-4α-methyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
27
(4αR,5S)-N-(3-fluoro-4-methylbenzyl)-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-
4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
28
(4αR,5S)-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-4α-methyl-N-(3,4,5-
trifluorobenzyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
29
(4αR,5S)-N-[2-(1-benzofuran-3-yl)-2-oxoethyl]-1-(4-fluorophenyl)-N-(2-
hydroxyethyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
30
(4αR,5S)-1-(4-fluorophenyl)-N-(2-hydroxyethy})-4α-methyl-N-{2-
[(phenylsulfonyl)methyl]benzyl}-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-
5-carboxamide
31
(4αR,5S)-N-[(5-chloro-1-benzothien-3-yl)methyl]-1-(4-fluorophenyl)-N-(2-
hydroxyethyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
32
(4αR,5S)-N-(3,5-difluorobenzyl)-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-4α-
methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
33
(4αR,5S)-N-(3-fluorobenzyl)-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-4α-
methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
34
(4αR,5S)-N-(3,5-dimethoxybenzyl)-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-4α-
methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
35
(4αR,5S)-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-4α-methyl-N-(2-phenylethyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
36
(4αR,5S)-N-benzyl-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-4α-methyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
37
(4αR,5S)-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-4α-methyl-N-propyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
38
(4αR,5S)-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-4α-methyl-N-pentyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
39
(4αR,5S)-N-butyl-1-(4-fluorophenyl)-4α-methyl-N-(2-oxoethyl)-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
40
(4αR,5S)-N-butyl-1-(4-fluorophenyl)-N-(2-hydroxypropyl)-4α-methyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
41
(4αR,5S)-N-(cyanomethyl)-1-(4-fluorophenyl)-N,4α-dimethyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
42
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-5-{[4-(trifluoromethyl)piperidin-1-
yl]carbonyl}-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole
43
(4αR,5S)-1-(4-fluorophenyl)-5-{[(2R)-2-(methoxymethyl)pyrrolidin-1-
yl]carbonyl}-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole
44
(4αR,5S)-N-cyclohexyl-1-(4-fluorophenyl)-N,4α-dimethyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
45
(4αR,5S)-1-(4-fluorophenyl)-N-(4-methoxybenzyl)-N-(2-methoxyethyl)-4α-
methyl-1,4,4α5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
46
(4αR,5S)-1-(4-fluorophenyl)-N,4α-dimethyl-N-[3-(trifluoromethyl)benzyl]-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
47
(4αR,5S)-1-(4-fluorophenyl)-N-(3-methoxybenzyl)-N,4α-dimethyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
48
(4αR,5S)-1-(4-fluorophenyl)-N,4α-dimethyl-N-(2-phenoxyethyl)-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
49
(4αR,5S)-N-benzyl-1-(4-fluorophenyl)-4α-methyl-N-(2-phenylethyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
50
(4αR,5S)-1-(4-fluorophenyl)-N-(2-methoxybenzyl)-N,4α-dimethyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
51
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-5-{[4-(phenylsulfonyl)piperidin-1-
yl]carbonyl}-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole
52
(4αR,5S)-N-benzyl-N-ethyl-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
53
(4αR,5S)-5-[(3,5-dimethylpiperidin-1-yl)carbonyl]-1-(4-fluorophenyl)-4α-
methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole
54
(4αR,5S)-1-(4-fluorophenyl)-N-isobutyl-N,4α-dimethyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
55
(4αR,5S)-N,N-diethyl-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
56
(4αR,5S)-N-butyl-1-(4-fluorophenyl)-4α-methyl-N-propyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
57
(4αR,5S)-1-(4-fluorophenyl)-N-isopropyl-4α-methyl-N-propyl-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
58
(4αR,5S)-1-(4-fluorophenyl)-N-isobutyl-4α-methyl-N-(3,3,3-trifluoro-2-
hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
59
(4αR,5S)-N-(2-fluorobenzyl)-1-(4-fluorophenyl)-4α-methyl-N-(3,3,3-trifluoro-
2-hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
60
(4αR,5S)-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-4α-methyl-N-(3,3,3-trifluoro-
2-hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
61
(4αR,5S)4-(4-fluorophenyl)-4α-methyl-N-propyl-N-(3,3,3-trifluoro-2-
hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
62
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-N-propyl-N-(tetrahydrofuran-2-
ylmethyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
63
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-N-propyl-N(tetrahydrofuran-2-
ylmethyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
64
(4αR,5S)-N-(cyclobutylmethyl)-1-(4-fluorophenyl)-4α-methyl-N-
(tetrahydrofuran-2-ylmethyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
65
(4αR,5S)-1-(4-fluorophenyl)-N-[(2S)-2-hydroxypropyl]-4α-methyl-N-propyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
66
(4αR,5S)-1-(4-fluorophenyl)-N-[(2S)-2-hydroxypropyl]-N-isobutyl-4α-methyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
67
(4αR,5S)-1-(4-fluorophenyl)-N-[(2R)-2-hydroxypropyl]-N-isobutyl-4α-methyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
68
(4αR,5S)-1-(4-fluorophenyl)-N-(2-hydroxyethyl)-4α-methyl-N-phenyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
69
(4αR,5S)-1-(4-fluorophenyl)-N-[2-(2-fluorophenyl)ethyl]-N-[(2S)-2-
hydroxypropyl]-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
70
(4αR,5S)-1-(4-fluorophenyl)-N,4α-dimethyl-N-(3,3,3-trifluoro-2-
hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
71
(4αR,5S)-N-ethyl-1-(4-fluorophenyl)-4α-methyl-N-(3,3,3-trifluoro-2-
hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
72
(4αR,5S)-N-ethyl-1-(4-fluorophenyl)-4α-methyl-N-(3,3,3-trifluoro-2-
hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
73
(4αR,5S)-1-(4-fluorophenyl)-N-[(2S)-2-hydroxypropyl]-4α-methyl-N-(3,3,3-
trifluoropropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
74
(4αR,5S)- N,4α-dimethyl-1-phenyl-N-(3,3,3-trifluoro-2-hydroxypropyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
75
(4αR,5S)-N,4α-dimethyl-1-phenyl-N-(3,3,3-trifluoro-2-hydroxypropyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
76
(4αR,5S)-N-ethyl-4α-methyl-1-phenyl-N-(3,3,3-trifluoro-2-hydroxypropyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
77
(4αR,5S)-N-ethyl-4α-methyl-1-phenyl-N-(3,3,3-trifluoro-2-hydroxypropyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
78
(4αR,5S)-4α-methyl-1-phenyl-N-propyl-N-(3,3,3-trifluoro-2-hydroxypropyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
79
(4αR,5S)-N-butyl-4α-methyl-1-phenyl-N-(3,3,3-trifluoro-2-hydroxypropyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
80
(4αR,5S)-N-isobutyl-4α-methyl-1-phenyl-N-(3,3,3-trifluoro-2-hydroxypropyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
81
(4αR,5S)-N-(cyclopropylmethyl)-4α-methyl-1-phenyl-N-(3,3,3-trifluoro-2-
hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
82
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-N-[2-(4-methylphenyl)ethyl]-N-(3,3,3-
trifluoro-2-hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
83
(4αR,5S)-1-(4-fluorophenyl)-N-[2-(2-methoxyphenyl)ethyl]-4α-methyl-N-
(3,3,3-trifluoro-2-hydroxypropyl)-1,4,4α,5,6,7-
hexahydrocyclopenta[f]indazole-5-carboxamide
84
(4αR,5S)-1-(4-fluorophenyl)-N-[2-(2-fluorophenyl)ethyl]-4α-methyl-N-(3,3,3-
trifluoro-2-hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
85
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-N-[2-(4-methylphenyl)ethyl]-N-(4,4,4-
trifluoro-2-hydroxybutyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
86
(4αR,5S)-1-(4-fluorophenyl)-N-[2-(2-methoxyphenyl)ethyl]-4α-methyl-N-
(4,4,4-trifluoro-2-hydroxybutyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-
5-carboxamide
87
(4αR,5S)-1-(4-fluorophenyl)-N-[2-(2-fluorophenyl)ethyl]-4α-methyl-N-(4,4,4-
trifluoro-2-hydroxybutyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
88
(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-N-propyl-N-(3,3,3-trifluoropropyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
89
(4αR,5S)-1-(4-fluorophenyl)-N-[(2R)-2-methoxypropyl]-N,4α-dimethyl-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
90
(4αR,5S)-1-(4-fluorophenyl)-N,4α-dimethyl-N-(3,3,3-trifluoropropyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
91
(4αR,5S)-N-ethyl-1-(4-fluorophenyl)-4α-methyl-N-(3,3,3-trifluoropropyl)-
1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-carboxamide
92
(4αR,5S)-1-(4-fluorophenyl)-N-[2-(2-fluorophenyl)ethyl]-4α-methyl-N-(3,3,3-
trifluoro-2-hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
93
(4αR,5S)-1-(4-fluorophenyl)-N-[2-(2-fluorophenyl)ethyl]-4α-methyl-N(3,3,3-
trifluoro-2-hydroxypropyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
94
(4αR,5S)-1-(4-fluorophenyl)-N-[2-(2-fluorophenyl)ethyl]-4α-methyl-N-(4,4,4-
trifluoro-2-hydroxybutyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
95
(4αR,5S)-1-(4-fluorophenyl)-N-[2-(2-fluorophenyl)ethyl]-4α-methyl-N-(4,4,4-
trifluoro-2-hydroxybutyl)-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazole-5-
carboxamide
or a pharmaceutically acceptable salt of any of the above.
11. A pharmaceutical composition comprising a compound according to claim 1 in combination with a pharmaceutically acceptable carrier.