US 8,299,048 B2Granted

Hexahydrocyclopentyl[f]indazole sulfonamides and derivatives thereof as selective glucocorticoid receptor modulators

AssigneeMerck Sharp & Dohme Corp.

InventorsWilliam P. Dankulich, Mildred L. Kaufman, Danielle M. McMaster, Robert S. Meissner, Helen J. Mitchell

Life of this patent

Estimating the term…

Abstract

The present invention is directed to hexahydrocyclopentylf]indazole 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.

Claims14

Dependent claims

A compound of Formula I

or a pharmaceutically acceptable salt thereof, wherein
R1 is selected from the group consisting of:
(a) C1-6alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) —CF3,
(3) hydroxyl,
(4) oxo,
(5) —CN, and
(6) pyridine,
(b) C2-6alkenyl, optionally mono-, di- or tri substituted with fluoro,
(c) —C3-6cycloalkyl,
(d) —C1-2alkylC3-6cycloalkyl,
(e) heterocycle,
(f) —C1-2alkylheterocycle,
(g) aryl selected from phenyl or naphthyl,
(h) —C1-2alkylaryl,
(i) —C2-4alkenylaryl,
(j) heteroaryl,
(k) —C1-2alkylheteroaryl,
(l) —Oheteroaryl,
(m) —OC1-6alkyl optionally mono-, di- or tri substituted with fluoro,
(n) —C1-4alkyl-O—C1-6alkyl, optionally substituted with hydroxy, or —O—S(O)2—C1-2alkyl-CF3,
(o) —OC3-6cycloalkyl, and
(p) —Oaryl,
wherein the heteroaryl, aryl and heterocycle of choices (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) —CF3,
(5) —C1-4alkyl,
(6) —OC1-4alkyl,
(7) —O—CH2CF3,
(8) heteroaryl selected from pyrazole, thiophene, imidazole, and oxazole, optionally substituted with 1, 2 or 3 substitutents independently selected from methyl CF3 and halo,
(9) —NH—OCH3,
(10) phenyl,
(11) —O-phenyl,
(12) pyridine,
(13) —O-pyridine,
(14) —NH—C(O)—NH—CH3,
(15) —NH—C(O)—C1-4alkyl,
(16) —NH—C(O)—C3-6cycloalkyl,
(17) —C1-3alkyl-C(O)—OH,
(18) —C1-3alkyl-C(O)—O—CH3,
(19) —C(O)—NH2,
(20) —C(O)—C1-4alkyl-NH2,
(21) —C(O)—NH—C3-6cycloalkyl,
(22) —C(O)—OH,
(23) —C(O)—O—C1-4alkyl,
(24) —C1-2alkyl-heterocycle,
(25) —C2-4alkenyl-C(O)-phenyl, and
(26) —O—S(O)2—C1-2alkyl-CF3;
R2 is selected from the group consisting of:
(a) H,
(b) OH,
(c) C1-8alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxyl,
(3) oxo,
(4) —CN,
(5) CHF2,
(6) CF3,
(7) pyridyl,
(8) —O—S(O)2—CF3, and
(9) —O—S(O)2—C1-2alkyl-CF3,
(d) C2-6alkenyl, optionally mono-, di- or tri substituted with fluoro,
(e) —C1-2alkylC3-6cycloalkyl,
(f) heterocycle,
(g) —C1-2alkylheterocycle,
(h) aryl selected from phenyl or naphthyl,
(i) —C1-3alkylaryl,
(j) —C2-4alkenylaryl,
(k) heteroaryl,
(l) —C1-2alkylheteroaryl,
(m) —CH2pyridyl, and
(o) —C1-4alkyl-O—C1-6alkyl, optionally substituted with hydroxy, or —O—S(O)2—C1-2alkyl-CF3,
wherein the cycloalkyl, heteroaryl, aryl and heterocycle of choices (e), (f), (g), (h), (i), (j), (k), (l) and (m) are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(1) hydroxyl,
(2) halo,
(3) —CN,
(4) —CF3,
(5) —C1-4alkyl,
(6) —OCH3,
(7) —O—CH2CF3,
(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—OCH3,
(10) phenyl,
(11) —O-phenyl,
(12) pyridine,
(13) —O-pyridine,
(14) —NH—C(O)—NH—CH3,
(15) —NH—C(O)—C1-4alkyl,
(16) —NH—C(O)—C3-6cycloalkyl,
(17) —C1-3alkyl-C(O)—OH,
(18) —C1-3alkyl-C(O)—O—CH3,
(19) —C(O)—NH2,
(20) —C(O)—C1-4alkyl-NH2,
(21) —C(O)—NH—C3-6cycloalkyl,
(22) —C(O)—OH,
(23) —C(O)—O—C1-4alkyl,
(24) —C1-2alkyl-heterocycle,
(25) —C2-4alkenyl-C(O)-phenyl, and
(26) —O—S(O)2—C1-2alkyl-CF3;
R3 is selected from
(a) H,
(b) C1-6alkyl,
(c) C3-6cycloalkyl, and
(d) C1-6fluoroalkyl;
and
R4 is hydrogen or F.

106 more elements

A compound selected from

N-{[(4αR,5S)-1-(4-Fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-pyridin-3-yl-N-(2-pyridin-2-ylethyl)methanesulfonamide,
N-(cyclopropylmethyl)-2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-allyl-2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-(cyclopropylmethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-2-(trifluoromethyl)benzenesulfonamide,
2-chloro-N-(cyclopropylmethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-5-(trifluoromethyl)benzenesulfonamide,
N-{4-[((cyclopropylmethyl){[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}amino)sulfonyl]phenyl}acetamide,
(5-chloro-N-(cyclopropylmethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1,3-dimethyl-1H-pyrazole-4-sulfonamide,
N-(cyclopropylmethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-4-methyl-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide,
N-(cyclopropylmethyl)-N-{[(4αR,5S-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-4-pentylbenzenesulfonamide,
N-(cyclopropylmethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}biphenyl-4-sulfonamide,
N-(cyolopropylmethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-3,5-dimethylisoxazole-4-sulfonamide,
2-chloro-N-(cyclopropylmethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
(E)-N-(cyclopropylmethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-2-phenylethylenesulfonamide,
2-chloro-N-(cyclopropylmethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-4-{[(methylamino)carbonyl]amino}benzenesulfonamide,
3-chloro-N-(cyclopropylmethyl)-4-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-(2-cyanoethyl)-2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2 -hydroxyethyl)benzenesulfonamide,
methyl 2-[((cyolopropylmethyl){[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}amino)sulfonyl]benzoate,
3-chloro-4-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)benzenesulfonamide,
3-chloro-N-(cyanomethyl)-4-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4a,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-(cyolopropylmethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-phenylmethanesulfonamide,
2-chloro-N-(cyclopropylmethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-5-methylisoxazole-4-sulfonamide,
4,5-dichloro-N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}thiophene-2-sulfonamide,
N-(cyanomethyl)-3,4-difluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
2,3-dichloro-N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
4-chloro-N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-3-(trifluoromethyl)benzenesulfonamide,
4-cyano-N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
4-chloro-N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-2,5-dimethylbenzenesulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-[3-(trifluoromethyl)phenyl]methanesulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-5-methylthiophene-2-sulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonamide,
(4αR,5S)-5-({(cyanomethyl)[(2,5-dimethyl-3-furyl)sulfonyl]amino}methyl)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-2-ium,
methyl 3-[((cyanomethyl){[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}amino)sulfonyl]thiophene-2-carboxylate,
(N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-5-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]thiophene-2-sulfonamide,
3-cyano-N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide,
4-(3-chloro-2-cyanophenoxy)-N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f ]indazol-5-yl]methyl}-4-methyl-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}naphthalene-1-sulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-2,5-bis(2,2,2-trifluoroethoxy)benzenesulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}biphenyl-4-sulfonamide,
N-(cyanomethyl)-2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-(cyanomethyl)-3,5-difluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-(cyanomethyl)N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-4-(pyridin-2-yloxy)benzenesulfonamide,
N-(cyanomethyl)-4-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-(cyanomethyl)-2,4,5-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methly}-1-phenylmethanesulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}2-methylbenzenesulfonamide,
2-chloro-N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-(cyanomethyl)-2,4-difluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
5-chloro-N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1,3-dimethyl-1H-pyrazole-4-sulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}biphenyl-2-sulfonamide,
N-(cyanomethyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-2-(trifluoromethyl)benzenesulfonamide,
2-cyano-N-(cyanomethyl)-N-{[(4αR ,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-5-methylisoxazole-4-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-5-(1,3-oxazol-5-yl)thiophene-2-sulfonamide,
3,4-diflouro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)benzenesulfonamide,
2-chloro-4-cyano-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)benzenesulfonamide,
2,3-dichloro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)benzenesulfonamide,
4-cyano-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)benzenesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-1-[3-(trifluoromethyl)phenyl]methanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-5- methylthiophene-2-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-1-methyl-3-(trifluoromethyl-1H-pyrazole-4-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-2,5-dimethylfuran-3-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-5-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]thiophene-2-sulfonamide,
3-cyano-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)benzenesulfonamide,
4-(3-chloro-2-cyanophenoxy)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)benzenesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-2-(trifluoromethyl)benzenesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-3,5-dimethylisoxazole-4-sulfonamide,
3,5-difluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)benzenesulfonamide,
methyl 2-{[{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}(2-hydroxyethyl)amino]sulfonyl}benzoate,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-4-(pyridin-2-yloxy)benzenesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-1-phenylmethanesulfonamide,
2-chloro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,4,4 ,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-4-{[(methylamino)carbonyl]amino}benzenesulfonamide,
N-{[(4αR ,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-2-methylbenzenesulfonamide,
2-cyano-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)benzenesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-4-phenoxybenzenesulfonamide,
2-chloro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-5-(trifluoromethyl)benzenesulfonamide,
2-chloro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)benzenesulfonamide,
2,4-difluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)benzenesulfonamide,
5-chloro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)-1,3-dimethyl-1H-pyrazole-4-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxyethyl)biphenyl-2-sulfonamide,
N-(4-{[{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}(2-hydroxyethyl)amino]sulfonyl}phenyl)acetamide,
2-fluoro-N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}propane-1-sulfonamide,
N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR ,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-[3-(trifluoromethyl)phenyl]methanesulfonamide,
2,2,2-trifluoro-N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}ethanesulfonamide,
2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(2-methoxyphenyl)ethyl]benzenesulfonamide,
2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(4-methylphenyl)ethyl]benzenesulfonamide,
N-[2-(2-chlorophenyl)ethyl]-2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
2,2,2-trifluoro-N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR)-1-(4-fluorophenyl)-4α-methyl-l,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}ethanesulfonamide,
2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-methoxyethyl)benzenesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-methoxyethyl)propane-1-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-methoxyethyl)methanesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-methoxyethyl)ethanesulfonamide,
N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR ,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonamide,
N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR ,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-2-(trifluoromethyl)benzenesulfonamide,
2-chloro-N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}benzenesulfonamide,
N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}cyclopropanesulfonamide,
N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}butane-1-sulfonamide,
N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-2-methylpropane-1-sulfonamide,
N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}octane-1-sulfonamide,
1-(2,4-dichlorophenyl)-N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}methanesulfonamide,
1-(3-chlorophenyl)-N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}methanesulfonamide,
1-(2-chlorophenyl)-N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}methanesulfonamide,
N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-[2-(trifluoromethyl)phenyl]methanesulfonamide,
N-(cyclopropylmethyl)-2,2,2-trifluoro-N-{1-[(4αR)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]ethyl}ethanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(tetrahydrofuran-2-ylmethyl)-1-[3-(trifluoromethyl)phenyl]methanesulfonamide,
1-(3,4-dichlorophenyl)-N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}methanesulfonamide,
3-chloro-4-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[(2S)-2-hydroxypropyl]benzenesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[(2S)-2-hydroxypropyl]ethanesulfonamide,
(1S)-2-{{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2,2,2-trifluoroethyl)sulfonyl]amino}-1-methylethyl 2,2,2-trifluoroethanesulfonate,
3-chloro-4-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[(2R)-2-hydroxypropyl]benzenesulfonamide,
2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(2-hydroxyphenyl)ethyl]benzenesulfonamde,
2-{[{[(4αR ,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl ]methyl}(2-hydroxyethyl)amino]sulfonyl}benzamide,
2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-methoxyethyl)ethanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(2-methoxyphenyl)ethyl]-1-[3-(trifluoromethyl)phenyl]methanesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(2-methoxyhenyl)ethyl]ethanesulfonamide,
2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}ethanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(2-hydroxyphenyl)ethyl]-1-[3-(trifluoromethyl)phenyl]methanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(2-hydroxyphenyl)ethyl]-3,5-dimethylisoxazole-4-sulfonamide,
N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-pyridin-3-ylmethanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(2-methoxyphenyl)ethyl]-1-pyridin-3-ylmethanesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(3-methoxyphenyl)ethyl]ethanesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(4-methoxyphenyl)ethyl]ethanesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-pyridin-2-ylethyl)ethanesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-pyridin-4-ylethyl)ethanesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(4-hydroxyphenyl)ethyl]ethanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[2-(2-hydroxyphenyl)ethyl]-1-pyridin-3-ylmethanesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(pyridazin-3-ylmethyl)ethanesulfonamide,
N-(3,3-difluoro-2-hydroxypropyl)-2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}ethanesulfonamide,
2,2-difluoro-1-({{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2,2,2-trifluoroethyl)sulfonyl]amino}methyl)ethyl 2,2,2-trifluoroethanesulfonate,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[(1-hydroxycyclopropyl)methyl]ethanesulfonamide,
1-({{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2,2,2-trifluoroethyl)sulfonyl]amino}methyl)cyclopropyl 2,2,2-trifluoroethanesulfonate,
2,2,2-trifluoro-N-[2-(2-fluorophenyl)ethyl]-N-{[(4αR,5S)-4α-methyl-1-phenyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}ethanesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-4α-methyl-1-phenyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-pyridin-2-ylethyl)ethanesulfonamide,
2,2,2-trifluoro-N-[2-(2-methoxyphenyl)ethyl]-N-{[(4αR,5S)-4α-methyl-1phenyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}ethanesulfonamide,
N-{[(4αR,5S)-4α-methyl-1-phenyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-pyridin-3-yl-N-(2-pyridin-2-ylethyl)methanesulfonamide,
N-[2-(2-hydroxyphenyl)ethyl]-N-{[(4αR,5S)-4α-methyl-1-phenyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-pyridin-3-ylmethanesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxy-2-pyridin-2-ylethyl)ethanesulfonamide,
2,2,2-trifluoro-N-{[(4αR ,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxy-2-pyridin-3-ylethyl)ethanesulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxy-2-pyridin-4-ylethyl)ethanesulfonamide,
2-{{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2,2,2-trifluoroethyl)sulfonyl]amino}-1-pyridin-2-ylethyl 2,2,2-trifluoroethanesulfonate,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-pyridin-3-ylpropyl)ethanesulfonamide,
N-(3-amino-4,4,4-trifluorobutyl)-2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}ethanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(3,3,3-trifluoro-2- hydroxypropyl)propane-1-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-pyridin-3-yl-N-(3,3,3-trifluoro-2-hydroxypropyl)methanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-methyl-N-(2-pyridin-2-ylethyl)-3-(trifluoromethyl)-1H-pyrazole-4-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-pyridin-2-ylethyl)propane-1-sulfonamide,
2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-pyridin-2-ylethyl)ethanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-pyridin-2-ylethyl)-1-[2-(trifluoromethyl)phenyl]methanesulfonamide,
N-(3,3-difluoro-2-hydroxypropyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-pyridin-3-ylmethanesulfonamide,
N-(3,3-difluoro-2-hydroxypropyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}propane-1-sulfonamide,
N-(3,3-difluoro-2-hydroxypropyl)-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonaimde,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxy-2-pyridin-2-ylethyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonamide,
2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-oxoethyl)benzenesulfonamide,
methyl 2-(2-{{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1-,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2,2,2-trifluoroethyl)sulfonyl]amino}ethyl)benzoate,
methyl 5-chloro-2-(2-{{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2,2,2-trifluoroethyl)sulfonyl]amino}ethyl)benzoate,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-3,5-dimethylisoxazole-4-sulfonamide,
methyl 2-{[{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}(3,3,3-trifluoro-2-hydroxypropyl)amino]sulfonyl}methyl)benzoate,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-{2-[2-(hydroxymethyl)phenyl]ethyl}ethanesulfonamide,
2-({[{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}(3,3,3-trifluoro-2-hydroxypropyl)amino]sulfonyl}methyl)benzoic acid,
N-{[(4αR ,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-pyridin-2-yl-N-(2-pyridin-2-ylethyl)methanesulfonaimde,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methly}-1-pyridin-4-yl-N-(2-pyridin-2-ylethyl)methanesulfonamide,
2-({[{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,4,5,6,7-hexahydrocyclopenta[f]1indazol-5-yl ]methyl}(3,3,3-trifluoro-2-hydroxypropyl)amino]sulfonyl}methyl)benzamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[(2R)-2-hydroxypropyl]-3,5-dimethylisoxazole-4-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-pyridin-3-ylmethanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-3,5-dimethyl-N-(tetrahydrofuran-2-ylmethyl)isoxazole-4-sulfoanmide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-methoxyethyl)ethanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-methoxyethyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-methoxyethyl)-3,5-dimethylisoxazole-4-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(tetrahydrofuran-2-ylmethyl)ethanesulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-1-methyl-N-(tetrahydrofuran-2-ylmethyl)-3-(trifluoromethyl)-1H-pyrazole-4-sulfonamide,
N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N,3,5-trimethylisoxazole-4-sulfonamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-methylethanesulfonamide,
N-ethyl-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-3,5-dimethylisoxazole-4-sulfonamide,
N-ethyl-2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}ethansulfonamide,
methyl 2-[({{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl,1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2R)-2-hydroxypropyl]amino}sulfonyl)methyl]benzoate,
methyl 2-[({{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl,1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2S)-2-hydroxypropyl]amino}sulfonyl)methyl]benzoate,
methyl 2-({[{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}(3,3,3-trifluoro-2-hydroxypropyl)amino]sulfonyl}methyl)benzoate,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-{2-[2-(hydroxymethyl)phenyl]ethyl}ethanesulfonamide,
2-[({{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2R)-2-hydroxypropyl]amino}sulfonyl)methyl]benzoic acid,
2-[({{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2R)-2-hydroxypropyl]amino}sulfonyl)methyl]benzoic acid,
2-[({{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2R)-2-hydroxypropyl]amino}sulfonyl)methyl]benzamide,
2-[({{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2R)-2-hydroxypropyl]amino}sulfonyl)methyl]benzamide,
methyl 2-({{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2R)-2-hydroxypropyl]amino}sulfonyl)benzoate,
methyl 2-({{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}[(2R)-2-hydroxypropyl]amino}sulfonyl)benzoate,
methyl 2-{[([(2-(2-fluorophenyl)ethyl]{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}amino)sulfonyl]methyl}benzoate,
methyl 2-[([2-(2-fluorophenyl)ethyl]{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}amino)sulfonyl]benzoate,
2-{[([2-(2-fluorophenyl)ethyl]{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}amino)sulfonyl]methyl}benzamide,
4-{[{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}(tetrahydrofuran-2-ylmethyl)amino]sulfonyl}benzamide,
3-[((2-fluorobenzyl){[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}amino)sulfonyl]benzamide,
2,2,2-trifluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(3-phenylpropyl)ethanesulfonamide,
N-{[(4αR,55)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-3,5-dimethyl-N-(3-phenylpropyl)isoxazole-4-sulfonamide,
2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(3-phenylpropyl)benzenesulfonamide,
2-({[{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}(2-pyridin-2-ylethyl)amino]sulfonyl}methyl)benzamide,
N-{1-[(4αR)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]ethyl}-1-pyridin-3-yl-N-(2-pyridin-2-ylethyl)methanesulfonamide,
2-({[{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}(2-hydroxyethyl)amino]sulfonyl}methyl)benzamide,
2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-(2-hydroxy-2-methylpropyl)benzenesulfonamide, and
2-fluoro-N-{[(4αR,5S)-1-(4-fluorophenyl)-4α-methyl-1,4,4α,5,6,7-hexahydrocyclopenta[f]indazol-5-yl]methyl}-N-[(1-hydroxycyclopropyl)methyl]benzenesulfonamide,
or a pharmaceutically acceptable salt thereof.

199 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/921,243Filed 24 Feb 2009 · us provisional application
Priority: 6 Mar 2008
Published: US 2011/0105440 A15 May 2011
Granted: 30 Oct 2012
Term ends: Not estimatedThe source records don’t support an estimate.

Classification44 codes

C07D 231/54
Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings: condensed with carbocyclic rings or ring systems
A61P 1/02
Drugs for disorders of the alimentary tract or the digestive system: stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 3/00
Drugs for disorders of the metabolism

Family

Application61/068,370Us provisional application · filed 6 Mar 2008
US 2011/0105440 A1Pre-grant publication · published 5 May 2011
US 8,299,048 B2This patent

From the US filing history. Foreign family members aren’t listed.

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

A compound of Formula I

or a pharmaceutically acceptable salt thereof, wherein
R1 is selected from the group consisting of:
(a) C1-6alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) —CF3,
(3) hydroxyl,
(4) oxo,
(5) —CN, and
(6) pyridine,
(b) C2-6alkenyl, optionally mono-, di- or tri substituted with fluoro,
(c) —C3-6cycloalkyl,
(d) —C1-2alkylC3-6cycloalkyl,
(e) heterocycle,
(f) —C1-2alkylheterocycle,
(g) aryl selected from phenyl or naphthyl,
(h) —C1-2alkylaryl,
(i) —C2-4alkenylaryl,
(j) heteroaryl,
(k) —C1-2alkylheteroaryl,
(l) —Oheteroaryl,
(m) —OC1-6alkyl optionally mono-, di- or tri substituted with fluoro,
(n) —C1-4alkyl-O—C1-6alkyl, optionally substituted with hydroxy, or —O—S(O)2—C1-2alkyl-CF3,
(o) —OC3-6cycloalkyl, and
(p) —Oaryl,
wherein the heteroaryl, aryl and heterocycle of choices (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) —CF3,
(5) —C1-4alkyl,
(6) —OC1-4alkyl,
(7) —O—CH2CF3,
(8) heteroaryl selected from pyrazole, thiophene, imidazole, and oxazole, optionally substituted with 1, 2 or 3 substitutents independently selected from methyl CF3 and halo,
(9) —NH—OCH3,
(10) phenyl,
(11) —O-phenyl,
(12) pyridine,
(13) —O-pyridine,
(14) —NH—C(O)—NH—CH3,
(15) —NH—C(O)—C1-4alkyl,
(16) —NH—C(O)—C3-6cycloalkyl,
(17) —C1-3alkyl-C(O)—OH,
(18) —C1-3alkyl-C(O)—O—CH3,
(19) —C(O)—NH2,
(20) —C(O)—C1-4alkyl-NH2,
(21) —C(O)—NH—C3-6cycloalkyl,
(22) —C(O)—OH,
(23) —C(O)—O—C1-4alkyl,
(24) —C1-2alkyl-heterocycle,
(25) —C2-4alkenyl-C(O)-phenyl, and
(26) —O—S(O)2—C1-2alkyl-CF3;
R2 is selected from the group consisting of:
(a) H,
(b) OH,
(c) C1-8alkyl, optionally mono-, di- or tri substituted with substituents independently selected from
(1) halo,
(2) hydroxyl,
(3) oxo,
(4) —CN,
(5) CHF2,
(6) CF3,
(7) pyridyl,
(8) —O—S(O)2—CF3, and
(9) —O—S(O)2—C1-2alkyl-CF3,
(d) C2-6alkenyl, optionally mono-, di- or tri substituted with fluoro,
(e) —C1-2alkylC3-6cycloalkyl,
(f) heterocycle,
(g) —C1-2alkylheterocycle,
(h) aryl selected from phenyl or naphthyl,
(i) —C1-3alkylaryl,
(j) —C2-4alkenylaryl,
(k) heteroaryl,
(l) —C1-2alkylheteroaryl,
(m) —CH2pyridyl, and
(o) —C1-4alkyl-O—C1-6alkyl, optionally substituted with hydroxy, or —O—S(O)2—C1-2alkyl-CF3,
wherein the cycloalkyl, heteroaryl, aryl and heterocycle of choices (e), (f), (g), (h), (i), (j), (k), (l) and (m) are optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
(1) hydroxyl,
(2) halo,
(3) —CN,
(4) —CF3,
(5) —C1-4alkyl,
(6) —OCH3,
(7) —O—CH2CF3,
(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—OCH3,
(10) phenyl,
(11) —O-phenyl,
(12) pyridine,
(13) —O-pyridine,
(14) —NH—C(O)—NH—CH3,
(15) —NH—C(O)—C1-4alkyl,
(16) —NH—C(O)—C3-6cycloalkyl,
(17) —C1-3alkyl-C(O)—OH,
(18) —C1-3alkyl-C(O)—O—CH3,
(19) —C(O)—NH2,
(20) —C(O)—C1-4alkyl-NH2,
(21) —C(O)—NH—C3-6cycloalkyl,
(22) —C(O)—OH,
(23) —C(O)—O—C1-4alkyl,
(24) —C1-2alkyl-heterocycle,
(25) —C2-4alkenyl-C(O)-phenyl, and
(26) —O—S(O)2—C1-2alkyl-CF3;
R3 is selected from
(a) H,
(b) C1-6alkyl,
(c) C3-6cycloalkyl, and
(d) C1-6fluoroalkyl;
and
R4 is hydrogen or F.

106 more elements

Facts

Application

12/921,243Filed 24 Feb 2009 · us provisional application

Priority

6 Mar 2008

Published

US 2011/0105440 A15 May 2011

Granted

30 Oct 2012

Term ends

Not estimatedThe source records don’t support an estimate.

Classification44 codes

C07D 231/54
Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings: condensed with carbocyclic rings or ring systems
A61P 1/02
Drugs for disorders of the alimentary tract or the digestive system: stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 3/00
Drugs for disorders of the metabolism