Nuclear Hormone Receptor Modulators
The invention provides a compound of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.
1 . A compound of Formula (I)
pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, isomers, and stereoisomers wherein
Ring A is optionally substituted aryl, optionally substituted saturated or partially unsaturated (C 5 -C 6 )carbocyclyl or optionally substituted heteroaryl;
Ring C is optionally substituted saturated or partially unsaturated (C 5 -C 6 )carbocyclyl or optionally substituted heterocyclyl;
Q and T are independently C or N, provided that both are not N;
Ring B is a seven membered ring wherein
X is —C(R 5 ) 2 —, —C(R 5 )—, —C(═O)—, —N(R a )—, —O—, —S—, —S(O)—, or —S(O) 2 —; or
when X is —C(R 5 ) 2 —, it can form a cyclopropyl ring spiro to the carbon atom to which it is attached;
Y is —C(R 5 ) 2 C(R 5 ) 2 —, —C(R 5 )C(R 5 ) 2 —, —C(R 5 ) 2 C(R 5 )—, —OC(R 5 ) 2 —, —N(R a )C(R 5 ) 2 —, —C(R 5 ) 2 N(R a )—, —C(═O)C(R 5 ) 2 —, —C(R 5 ) 2 C(═O)—, —O—C(═O)—, —C(═O)—O—, or —C(R 5 ) 2 —O—; or
Y is —C(R 5 ) 2 — when Q or T is N;
Z is CR 4 or N; or
Ring B is a six membered ring wherein
Y is —C(R 5 ) 2 —;
Q or T must be N;
Z is CR 4 or N; or
when X is —C(R 5 ) 2 —, it can form a cyclopropyl ring spiro to the carbon atom to which it is attached;
provided that X—Y or Y—Z do not form O—O, N—N, N—O, C(═O)—C(═O), N—C—O or O—C—O bonds; and
provided that in X—Y a sulfur atom is not adjacent to an oxygen atom or —C(═O);
provided that X—Y does not form —O—C(R 5 ) 2 —O—, —N—C(R 5 ) 2 —O— or —S—C(R 5 ) 2 —O—;
R 1 is H, Br, Cl, F, —COOR a , —OR a , —O-optionally substituted (C 1 -C 3 )alkylene-optionally substituted aryl, —O-optionally substituted (C 1 -C 3 )alkylene-optionally substituted heteroaryl, —O-optionally substituted (C 1 -C 3 )alkylene-optionally substituted heterocyclyl, optionally substituted (C 1 -C 3 )alkyl, optionally substituted aryl, optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —C(O)N(R a )(CH 2 ) r —R b , —N(R a )C(O)(CH 2 ) r —R b , —S(O) 2 N(R a )—R b —N(R a )S(O) 2 —R b , —O—S(O) 2 —CF 3 , —N(R a )-optionally substituted (C 3 -C 6 )cycloalkyl, —N(R a )-optionally substituted heterocyclyl, —N(R a )-optionally substituted heteroaryl, —N(R a )-optionally substituted aryl,
R 2 is —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl;
R 3 is independently H, deuterium, —CD 3 , —CF 3 , optionally substituted (C 2 -C 6 )alkynyl, oxo, —OR a , —OP(═O)(OH)(OH), optionally substituted (C 1 -C 4 )alkyl, —(C(R a ) 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, —(C(R a ) 2 ) r -optionally substituted aryl, —(C(R a ) 2 ) r -optionally substituted heteroaryl, —(C(R a ) 2 ) r —N(R a )-optionally substituted heteroaryl, a carbocyclic or heterocyclic spirocyclic moiety attached to ring C;
R 4 is H, optionally substituted (C 1 -C 3 )alkyl, OH or —O-optionally substituted (C 1 -C 3 )alkyl;
R 5 is independently H, F, N(R a ), OR a , optionally substituted (C 3 -C 6 )cycloalkyl, or optionally substituted (C 1 -C 3 )alkyl;
R a is independently H, optionally substituted (C 3 -C 6 )cycloalkyl or optionally substituted (C 1 -C 3 )alkyl;
R b is H, optionally substituted (C 1 -C 3 )alkyl, optionally substituted aryl, optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted heteroaryl or optionally substituted heterocyclyl;
m is 1, 2, 3 or 4;
n is 1, 2, 3 or 4; and
r is independently 0, 1 or 2.
2 . The compound of claim 1 wherein the compound is of Formula (I)a or Formula (I)b
3 . The compound of claim 2 wherein Ring A is optionally substituted phenyl, optionally substituted pyrrolyl, or optionally substituted pyrazolyl.
4 . The compound of claim 3 wherein Ring C is optionally substituted cyclohexyl or optionally substituted cyclohexenyl.
5 . The compound of claim 4 wherein X is —C(R 5 ) 2 —, —C(R 5 )—, —C(═O)—, —O— or —N(R a )—.
6 . The compound of claim 5 wherein R 1 is —COOR a , OR a , optionally substituted (C 1 -C 3 )alkyl, —C(O)N(R a )(CH 2 ) r —R b , —N(R a )C(O)(CH 2 ) r —R b , optionally substituted azabenzimidazolyl, optionally substituted benzimidazolyl, —O-optionally substituted (C 1 -C 3 )alkylene-optionally substituted phenyl, or —O-optionally substituted (C 1 -C 3 )alkylene-optionally substituted pyridinyl.
7 . The compound of claim 6 wherein R 2 is —CH 2 CF 3 , —(CH 2 ) r -optionally substituted aryl, or optionally substituted (C 1 -C 3 )alkyl.
8 . The compound of claim 7 wherein R 3 is independently H, —CF 3 , —C≡CCH 3 , oxo, —OR a , —OP(═O)(OH)(OH), optionally substituted (C 1 -C 4 )alkyl, —(C(R a ) 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, or —(CH 2 ) r -optionally substituted aryl.
9 . The compound of claim 8 wherein R 3 is independently H, —CF 3 , —C≡CCH 3 , oxo, —OR a , optionally substituted (C 1 -C 4 )alkyl, —CH 2 -optionally substituted cyclopropyl, —CH 2 -optionally substituted phenyl, or -optionally substituted phenyl.
10 . The compound of claim 9 wherein R b is H, optionally substituted azetidinyl, optionally substituted phenyl, optionally substituted piperidinyl, optionally substituted pyrimidinyl, optionally substituted pyridinyl, optionally substituted pyrazolyl, optionally substituted pyrrolidinyl or optionally substituted tetrazolyl.
11 . The compound of claim 10 wherein Q is C.
12 . The compound of claim 11 wherein T is C.
13 . A compound of Formula (I) wherein the compound is
(4aR,11bS)-11b-benzyl-9-hydroxy-1,2,4,4a,5,6,7,11b-octahydro-dibenzo[a,c]cyclohepten-3-one; compound with (4aS,11bR)-11b-benzyl-9-hydroxy-1,2,4,4a,5,6,7,11b-octahydro-dibenzo[a,c]cyclohepten-3-one;
(3R,4aS,11bS)-11b-Benzyl-3-methyl-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cycloheptene-3,9-diol; compound with (3S,4aR,11bR)-11b-benzyl-3-methyl-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cycloheptene-3,9-diol;
(3R,4aR,11bR)-11b-benzyl-3-methyl-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cycloheptene-3,9-diol; compound with (3S,4aS,11bS)-11b-benzyl-3-methyl-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cycloheptene-3,9-diol;
(7aS,11aS)-11a-Benzyl-9-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,11aR)-11a-benzyl-9-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aS)-11a-benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9R,11aR)-11a-benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aR)-11a-benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aS)-11a-Benzyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9R,11aR)-11a-benzyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-benzyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-methoxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-benzyl-9-hydroxy-9-methoxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,11aS)-11a-Benzyl-9-hydroxy-N-(2-methylpyridin-3-yl)-6-oxo-9-(trifluoromethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[b,d]azepine-3-carboxamide;
(4aS,11bS)-11b-benzyl-3-hydroxy-N-(2-methylpyridin-3-yl)-7-oxo-3-(trifluoromethyl)-2,3,4,4 a,5,6,7,11b-octahydro-1H-dibenzo[c,e]azepine-9-carboxamide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-5-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-benzyl-9-ethyl-9-hydroxy-5-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-5-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aR)-11a-benzyl-9-ethyl-9-hydroxy-5-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aS)-9-Ethyl-9-hydroxy-11a-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aS,9R,11aR)-9-ethyl-9-hydroxy-11a-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9R,11aS)-9-ethyl-9-hydroxy-11a-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aS,9S,11aR)-9-ethyl-9-hydroxy-11a-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(3S,4aS,11bS)-11b-Benzyl-3-prop-1-ynyl-2,3,4,4 a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cycloheptene-3,9-diol; compound with (3R,4 aR,11bR)-11b-benzyl-3-prop-1-ynyl-2,3,4,4 a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cycloheptene-3,9-diol;
(7aS,9S,11aS)-11a-Benzyl-9-hydroxy-9-prop-1-ynyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9R,11aR)-11a-benzyl-9-hydroxy-9-prop-1-ynyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-methyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-benzyl-9-hydroxy-9-methyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-benzyl-9-hydroxy-9-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aS)-11a-Benzyl-9-ethynyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aS,9S,11aS)-11a-benzyl-9-ethynyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethoxymethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-benzyl-9-ethoxymethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-9-Benzyl-9-hydroxy-11a-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aS)-9-benzyl-9-hydroxy-11a-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aR)-9-benzyl-9-hydroxy-11a-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9R,11aS)-9-benzyl-9-hydroxy-11a-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(6aS,8R,10aS)-10a-Benzyl-8-ethyl-1-methyl-1,4,5,6,6a,7,8,9,10,10a-decahydro-1,2-diaza-benzo[e]azulen-8-ol; compound with (6aR,8S,10aR)-10a-benzyl-8-ethyl-1-methyl-1,4,5,6,6a,7,8,9,10,10a-decahydro-1,2-diaza-benzo[e]azulen-8-ol;
(6aS,8S,10aS)-10a-Benzyl-8-ethyl-1-methyl-1,4,5,6,6a,7,8,9,10,10a-decahydro-1,2-diaza-benzo[e]azulen-8-ol; compound with (6aR,8R,10aR)-10a-benzyl-8-ethyl-1-methyl-1,4,5,6,6a,7,8,9,10,10a-decahydro-1,2-diaza-benzo[e]azulen-8-ol;
(6aS,8R,10 aS)-10a-Benzyl-8-ethyl-2-methyl-2,4,5,6,6a,7,8,9,10,10a-decahydro-1,2-diaza-benzo[e]azulen-8-ol; compound with (6aR,8S,10aR)-10a-benzyl-8-ethyl-2-methyl-2,4,5,6,6a,7,8,9,10,10a-decahydro-1,2-diaza-benzo[e]azulen-8-ol;
(6aS,8S,10 aS)-10a-benzyl-8-ethyl-2-methyl-2,4,5,6,6a,7,8,9,10,10a-decahydro-1,2-diaza-benzo[e]azulen-8-ol; compound with (6aR,8R,10aR)-10a-benzyl-8-ethyl-2-methyl-2,4,5,6,6a,7,8,9,10,10a-decahydro-1,2-diaza-benzo[e]azulen-8-ol;
(2R,3R,4aS,11bR)-11b-Benzyl-3-phenyl-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cycloheptene-2,3,9-triol compound with (2S,3S,4aR,11bS)-11b-benzyl-3-phenyl-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cycloheptene-2,3,9-triol;
(7aS,9R,10R,11aR)-11a-Benzyl-9,10-dihydroxy-9-phenyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,10S,11aS)-11a-benzyl-9,10-dihydroxy-9-phenyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aS)-11a-Ethyl-9-hydroxy-9-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-11a-Ethyl-9-hydroxy-9-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aS)-9,11a-Diethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-9,11a-Diethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9R,11aS)-11a-Ethyl-9-hydroxy-9-isobutyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aR)-11a-Ethyl-9-hydroxy-9-isobutyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9R,11aS)-9-Cyclopropylmethyl-11a-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aR)-9-Cyclopropylmethyl-11a-ethyl-9-hydroxy-6,7,7a, 8,9,10,11,11a-octahydro-5H-dibenzo[a,e]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-9-Hydroxy-9-propyl-11a-(2,2,2-trifluoro-ethyl)-6,7,7a, 8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-9-hydroxy-9-propyl-11a-(2,2,2-trifluoro-ethyl)-6,7,7a, 8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aR)-11a-Ethyl-9-hydroxy-9-isobutyl-6,7,7a,8,9,10,11,11a-octahydro-5-oxa-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9R,11aS)-11a-Ethyl-9-hydroxy-9-isobutyl-6,7,7a,8,9,10,11,11a-octahydro-5-oxa-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aR)-9-Cyclopropylmethyl-11a-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5-oxa-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9R,11aS)-9-Cyclopropylmethyl-11a-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5-oxa-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aR)-11a-Ethyl-9-hydroxy-9-isobutyl-6,7,7a,8,9,10,11,11a-octahydro-5-oxa-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9R,11aS)-11a-Ethyl-9-hydroxy-9-isobutyl-6,7,7a,8,9,10,11,11a-octahydro-5-oxa-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aR)-9-Cyclopropylmethyl-11a-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5-oxa-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-9-Cyclopropylmethyl-11a-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5-oxa-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-9-Hydroxy-9-propyl-11a-(2,2,2-trifluoro-ethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aR)-9-Hydroxy-9-propyl-11a-(2,2,2-trifluoro-ethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aS)-11a-Ethyl-9-hydroxy-9-methyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-11a-ethyl-9-hydroxy-9-methyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9R,11aS)-11a-Ethyl-9-hydroxy-5-oxo-9-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aR)-11a-Ethyl-9-hydroxy-5-oxo-9-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aS)-9-Hydroxy-9-isobutyl-11a-(2,2,2-trifluoro-ethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9R,11aR)-9-hydroxy-9-isobutyl-11a-(2,2,2-trifluoro-ethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-9-Cyanomethyl-11a-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aS)-9-cyanomethyl-11a-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-cyanomethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-Benzyl-9-cyanomethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-cyanomethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aR)-11a-Benzyl-9-cyanomethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2,4-dimethyl-pyrimidin-5-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (3,5-dimethyl-pyrazin-2-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (3-methyl-pyridin-4-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2,6-dimethyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c a,c]cycloheptene-3-carboxylic acid (3-methyl-pyridin-2-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid [1,3,4]thiadiazol-2-ylamide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-2H-pyrazol-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2,5-dimethyl-2H-pyrazol-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2,4-dimethyl-pyrimidin-5-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (1-methyl-1H-tetrazol-5-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (5-methyl-2H-pyrazol-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-ylmethyl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-morpholin-4-yl-ethyl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (1-methyl-4-oxo-4,5-dihydro-1H-imidazol-2-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-ethyl-2H-pyrazol-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid [2-methyl-6-(2H-pyrazol-3-yl)-pyridin-3-yl]-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid [2-methyl-6-(1H-pyrazol-4-yl)-pyridin-3-yl]-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid methyl-(2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-11a-Ethyl-9-hydroxy-9-(2,2,2-trifluoro-ethoxymethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide: compound with (7aR,9S,11aS)-11a-ethyl-9-hydroxy-9-(2,2,2-trifluoro-ethoxymethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethoxymethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aR)-11a-Benzyl-9-ethoxymethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-(2,2,2-trifluoro-ethoxymethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR-11a-Benzyl-9-hydroxy-9-(2,2,2-trifluoro-ethoxymethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-(oxetan-3-ylmethoxymethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-Benzyl-9-hydroxy-9-(oxetan-3-ylmethoxymethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-isopropoxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-Benzyl-9-hydroxy-9-isopropoxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-prop oxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aR-11a-Benzyl-9-hydroxy-9-prop oxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-(2,2,2-trifluoro-1-methyl-ethoxymethyl)-5,7,7a,8,9,10,11,11a-octahydro-dibenzo[c,e]oxepine-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-Benzyl-9-hydroxy-9-(2,2,2-trifluoro-1-methyl-ethoxymethyl)-5,7,7a,8,9,10,11,11a-octahydro-dibenzo[c,e]oxepine-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-prop oxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR-11a-Benzyl-9-hydroxy-9-propoxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-(tetrahydro-pyran-4-yloxymethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-Benzyl-9-hydroxy-9-(tetrahydro-pyran-4-yloxymethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-phenoxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-Benzyl-9-hydroxy-9-phenoxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-hydroxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-Benzyl-9-hydroxy-9-hydroxymethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-9-(2-methanesulfonyl-ethoxymethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-Benzyl-9-hydroxy-9-(2-methanesulfonyl-ethoxymethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-9-Ethoxymethyl-11a-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aS)-9-ethoxymethyl-11a-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-9-Ethoxymethyl-11a-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aS)-9-ethoxymethyl-11a-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(4aS,11bS)-11b-Benzyl-6-methyl-N-(2-methylpyridin-3-yl)-3-oxo-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[c,e]azepine-9-carb oxamide;
(3S,4aS,11bS)-11b-benzyl-3-hydroxy-6-methyl-N-(2-methylpyridin-3-yl)-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[c,e]azepine-9-carboxamide;
(7aS,11aS)-11a-Benzyl-N-(2-methylpyridin-3-yl)-7,9-dioxo-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-N-(2-methylpyridin-3-yl)-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-N-(2-methylpyridin-3-yl)-5-oxo-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide;
(7aR,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-11a-Ethyl-9-hydroxy-N-(2-methylpyridin-3-yl)-9-propyl-6,7,7a,8,9,10,11,11a-octahydrodibenzo[b,d]oxepine-3-carboxamide; compound with (7aR,9S,11aS)-11a-ethyl-9-hydroxy-N-(2-methylpyridin-3-yl)-9-propyl-6,7,7a,8,9,10,11,11a-octahydrodibenzo[b,d]oxepine-3-carboxamide;
(7aR,9S,11aS)-11a-ethyl-9-hydroxy-N-(2-methylpyridin-3-yl)-9-propyl-6,7,7a,8,9,10,11,11a-octahydrodibenzo[b,d]oxepine-3-carboxamide;
(7aS,9R,11aR)-11a-ethyl-9-hydroxy-N-(2-methylpyridin-3-yl)-9-propyl-6,7,7a,8,9,10,11,11a-octahydrodibenzo[b,d]oxepine-3-carboxamide;
(7aS,9R,11aR)-11a-Ethyl-9-hydroxy-9-phenyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aS)-11a-ethyl-9-hydroxy-9-phenyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,10R,11aR)-11a-Ethyl-9,10-dihydroxy-9-phenyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,10S,11aS)-11a-Ethyl-9,10-dihydroxy-9-phenyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-amino-phenyl)-amide;
(3R,4aS,11bS)-9-(1H-benzoimidazol-2-yl)-11b-benzyl-3-ethyl-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cyclohepten-3-ol;
(7aS,9R,11aR)-11a-Ethyl-9-hydroxy-9-propyl-7a,8,9,10,11,11a-hexahydro-7H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide compound with (7aR,9S,11aS)-11a-ethyl-9-hydroxy-9-propyl-7a,8,9,10,11,11a-hexahydro-7H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-11a-Ethyl-9-hydroxy-9-propyl-7a,8,9,10,11,11a-hexahydro-7H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aS)-11a-ethyl-9-hydroxy-9-propyl-7a,8,9,10,11,11a-hexahydro-7H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-7a,8,9,10,11,11a-hexahydro-7H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aR)-11a-Benzyl-9-ethyl-9-hydroxy-7a,8,9,10,11,11a-hexahydro-7H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aR)-11a-Ethyl-9-hydroxy-9-(3,3,3-trifluoro-propyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9R,11aS)-11a-ethyl-9-hydroxy-9-(3,3,3-trifluoro-propyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-11a-Ethyl-9-hydroxy-N-(2-methylpyridin-3-yl)-9-phenyl-6,7,7a,8,9,10,11,11a-octahydrodibenzo[b,d]oxepine-3-carboxamide; compound with (7aR,9S,11aS)-11a-ethyl-9-hydroxy-N-(2-methylpyridin-3-yl)-9-phenyl-6,7,7a,8,9,10,11,11a-octahydrodibenzo[b,d]oxepine-3-carboxamide;
(7aS,9R,10R,11aR)-11a-Ethyl-9,10-dihydroxy-N-(2-methylpyridin-3-yl)-9-phenyl-6,7,7a,8,9,10,11,11a-octahydrodibenzo[b,d]oxepine-3-carboxamide; compound with (7aR,9S,10S,11aS)-11a-ethyl-9,10-dihydroxy-N-(2-methylpyridin-3-yl)-9-phenyl-6,7,7a,8,9,10,11,11a-octahydrodibenzo[b,d]oxepine-3-carboxamide;
(7aS,9R,11aR)-11a-Ethyl-9-propyl-9-hydroxy-N-(2-methylpyridin-3-yl)-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide; compound with (7aR,9S,11aS)-11a-ethyl-9-propyl-9-hydroxy-N-(2-methylpyridin-3-yl)-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide;
(7aR,9S,11aS)-11a-ethyl-9-propyl-9-hydroxy-N-(2-methylpyridin-3-yl)-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide;
(7aS,9R,11aR)-11a-Ethyl-9-propyl-9-hydroxy-N-(2-methylpyridin-3-yl)-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide;
(7aS,9S,11aR)-11a-Ethyl-9-hydroxy-9-isobutyl-5,7,7a,8,9,10,11,11a-octahydro-dibenzo[c,e]oxepine-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-9,11a-diethyl-9-hydroxy-N-(2-methylpyridin-3-yl)-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide;
(7aR,9S,11aS)-9,11a-diethyl-9-hydroxy-N-(2-methylpyridin-3-yl)-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide;
(7aR,9S,11aS)-9,11a-diethyl-9-hydroxy-N-(2-methylpyridin-3-yl)-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (4-amino-phenyl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (3-amino-phenyl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-benzo[c]pyrrolo[1,2-a]azepine-2-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-benzo[c]pyrrolo[1,2-a]azepine-2-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-amino-phenyl)-amide; compound with (7aR,9S,11aR)-11a-benzyl-9-ethyl-9-hydroxy-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-amino-phenyl)-amide;
(3R,4aS,11bS)-9-(1H-Benzoimidazol-2-yl)-11b-benzyl-3-ethyl-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cyclohepten-3-ol; compound with (3S,4aR,11bR)-9-(1H-benzoimidazol-2-yl)-11b-benzyl-3-ethyl-2,3,4,4 a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cyclohepten-3-ol;
(3R,4aS,11bS)-9-(1H-Benzoimidazol-2-yl)-11b-benzyl-3-ethyl-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cyclohepten-3-ol;
(3S,4aR,11bR)-9-(1H-benzoimidazol-2-yl)-11b-benzyl-3-ethyl-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[a,c]cyclohepten-3-ol;
(7aS,9R,11aR)-11a-Ethyl-9-hydroxy-9-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-amino-pyridin-3-yl)-amide; compound with (7aR,9S,11aS)-11a-Ethyl-9-hydroxy-9-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-amino-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Cyclopropylmethyl-9-hydroxy-9-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aR,9S,11aR)-11a-cyclopropylmethyl-9-hydroxy-9-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; or
(7aS,9R,11aR)-11a-Ethyl-9-hydroxy-9-propyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-chloro-phenyl)-amide.
14 . The compound of claim 1 wherein the compound is of Formula (I)c or Formula (I)d
15 . The compound of claim 14 wherein Ring A is optionally substituted phenyl, optionally substituted pyrazolyl or optionally substituted pyrrolyl.
16 . The compound of claim 15 wherein Ring C is optionally substituted cyclohexyl or optionally substituted cyclohexenyl.
17 . The compound of claim 16 wherein X is —C(R 5 ) 2 —, —C(R 5 )—, —C(═O)—, —O— or —N(R a )—.
18 . The compound of claim 17 wherein Y is —C(R 5 ) 2 C(R 5 ) 2 —, —C(R 5 )C(R 5 ) 2 —, —C(R 5 ) 2 C(R 5 )—, —OC(R 5 ) 2 —, —N(R a )C(R 5 ) 2 —, —C(R 5 ) 2 N(R a )—, —C(═O)C(R 5 ) 2 —, —C(R 5 ) 2 C(═O)—, —O—C(═O)—, —C(═O)—O—, —C(R 5 ) 2 —O—, —O—C(R 5 ) 2 — or —O—C(R 5 )(R b ).
19 . The compound of claim 18 wherein R 1 is —COOR a , OR a , —O-optionally substituted (C 1 -C 3 )alkylene-optionally substituted phenyl, —O-optionally substituted (C 1 -C 3 )alkylene-optionally substituted pyridinyl, optionally substituted (C 1 -C 3 )alkyl, —C(O)N(R a )(CH 2 ) r —R b , or —N(R a )C(O)(CH 2 ) r —R b .
20 . The compound of claim 19 wherein R 2 is —(CH 2 ) r -optionally substituted phenyl, -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl.
21 . The compound of claim 20 wherein R 3 is independently H, —CF 3 , optionally substituted (C 2 -C 6 )alkynyl, oxo, —OR a , —OP(═O)(OH)(OH), optionally substituted (C 1 -C 4 )alkyl, —CH 2 -optionally substituted cyclopropyl, or optionally substituted phenyl.
22 . The compound of claim 21 wherein R b is optionally substituted phenyl, -optionally substituted pyrimidinyl, optionally substituted pyridinyl, optionally substituted pyrazolyl or optionally substituted tetrazolyl.
23 . The compound of claim 22 wherein Q is C.
24 . The compound of claim 23 wherein T is C.
25 . A compound of Formula (I) wherein the compound is
(4aS,11bS)-11b-Benzyl-9-hydroxy-1,2,4,4 a,5,6,7,11b-octahydro-dibenzo[a,c]cyclohepten-3-one; compound with (4aR,11bR)-11b-benzyl-9-hydroxy-1,2,4,4a,5,6,7,11b-octahydro-dibenzo[a,c]cyclohepten-3-one;
(7aR,11aS)-11a-Benzyl-9-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aS,11aR)-11a-benzyl-9-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9R,11aS)-11a-Benzyl-9-hydroxy-9-methyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aS,9S,11aR)-11a-benzyl-9-hydroxy-9-methyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9S,11aS)-11a-benzyl-9-hydroxy-9-methyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (7aS,9R,11aR)-11a-benzyl-9-hydroxy-9-methyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aS)-11a-Benzyl-9-hydroxy-N-(2-methylpyridin-3-yl)-6-oxo-9-(trifluoromethyl)-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[b,c1]azepine-3-carboxamide;
(7aR,9R,11aS)-11a-Benzyl-9-hydroxy-9-trifluoromethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-2H-pyrazol-3-yl)-amide;
(7aR,9R,11aS)-11a-Benzyl-9-hydroxy-9-trifluoromethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (3-methyl-pyridin-4-yl)-amide;
(7aS,9S,11aR)-11a-Benzyl-9-hydroxy-9-trifluoromethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-2H-pyrazol-3-yl)-amide;
(7aS,9R,11aS)-11a-benzyl-9-hydroxy-9-methyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9R,11aR)-11a-benzyl-9-hydroxy-9-methyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aR,9R,11aS)-11a-Benzyl-9-hydroxy-9-trifluoromethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(7aS,9S,11aR)-11a-Benzyl-9-hydroxy-9-trifluoromethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide;
(3R,4aR,11bS)-11b-Benzyl-3-ethyl-3-hydroxy-6-methyl-N-(2-methylpyridin-3-yl)-7-oxo-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[c,e]azepine-9-carboxamide;
(7aR,9R,11aS)-11a-Benzyl-9-hydroxy-N-(2-methylpyridin-3-yl)-5-oxo-9-(trifluoromethyl)-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide;
(7aR,9R,11aS)-11a-Benzyl-9-hydroxy-N-(2-methylpyridin-3-yl)-9-(trifluoromethyl)-5,7,7a,8,9,10,11,11a-octahydrodibenzo[c,e]oxepine-3-carboxamide;
(3R,4aR,11bS)-11b-Benzyl-3-hydroxy-6-methyl-N-(2-methylpyridin-3-yl)-3-(trifluoromethyl)-2,3,4,4a,5,6,7,11b-octahydro-1H-dibenzo[c,e]azepine-9-carboxamide; or
(7aR,9R,11aS)-11a-Benzyl-9-hydroxy-5-oxo-9-trifluoromethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide.
26 . The compound
11b-Benzyl-9-methoxy-1,2,5,6,7,11b-hexahydro-dibenzo[a,c]cyclohepten-3-one;
11b-Benzyl-9-hydroxy-1,2,5,6,7,11b-hexahydro-dibenzo[a,c]cyclohepten-3-one;
(9R,11aS)-11a-Benzyl-9-hydroxy-9-methyl-6,7,9,10,11,11a-hexahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; compound with (9S,11aR)-11a-benzyl-9-hydroxy-9-methyl-6,7,9,10,11,11a-hexahydro-5H-dibenzo[a,c]cycloheptene-3-carboxylic acid (2-methyl-pyridin-3-yl)-amide; or
(4aS,9aS)-4a-Benzyl-octahydro-benzocycloheptene-2,5-dione; compound with (4aR,9aR)-4a-benzyl-octahydro-benzocycloheptene-2,5-dione.
27 . A pharmaceutical composition comprising a compound of Formula (I) and a pharmaceutically acceptable carrier or excipient.
28 . A method of treating a disease or condition comprising administering a therapeutically effective amount of a compound of Formula (I).
29 . The method of claim 28 wherein the disease or condition to be treated is acquired immunodeficiency syndrome (AIDS), acute adrenal insufficiency, addiction, Addison's Disease, adrenal function, allergic rhinitis, allergies, Alzheimer's, anorexia, angioneurotic edema, ankylosing spondylitis, anxiety, asthma, auto-immunity, autoimmune chronic active hepatitis, autoimmune diseases, blepharitis, bursitis, cachexia, cardiovascular disease, cerebral edema, choroidal neovascularization due to age-related macular degeneration, chronic kidney disease, chronic obstructive pulmonary disease, chronic primary adrenal insufficiency, chronic retinal detachment, compulsive behavior, congenital adrenal hyperplasia, cognitive dysfunction, conjunctivitis, cirrhosis, Crohn's disease, Cushing's syndrome, depression, diabetes, diabetes mellitus, diabetic microangiopathy, diabetic neuropathy, diabetic retinopathy, dry eye syndrome, frailty, giant cell arteritis, glaucoma, granulomatous polyarteritis, hay fever, hepatitis, HPA axis suppression and regulation, human immunodeficiency virus (HIV), hypercalcemia, hypercortisolemia, hypergylcemia, hypertension, immune proliferation/apoptosis, immunodeficiency, immunomodulation, inflammation, inflammation of the eye, inflammatory bowel disease, inhibition of myeloid cell lines, insulin dependent diabetes mellitus, insulin-dependent diabetes mellitus glaucoma, insulin resistance, iridocyclitis, juvenile idiopathic arthritis, juvenile rheumatoid arthritis, leukemia, Little's syndrome, lupus, lymphoma, macular degeneration, macular edema, a malignancy, medical catabolism, multi-drug resistance, multiple sclerosis, neurodgeneration, obesity, ocular or macular edema, ocular neovascular disease, organ transplantation, modulation of the Th1/Th2 cytokine balance, optic neuritis, optic pits, neuropathy, osteoarthritis, osteoporosis, Parkinson's, plaque psoriasis, polyarteritis nodosa, post-laser treatment complications, post-surgical bone fracture, post-traumatic stress syndrome, prevention of muscle frailty, psoriasis, psoriatic arthritis, psychosis, regulation of carbohydrate, protein and lipid metabolism, regulation of electrolyte and water balance, regulation of functions of the cardiovascular, kidney, central nervous, immune, or skeletal muscle systems, retinopathy of prematurity, rheumatic fever, rheumatoid arthritis, rhinitis, scleritis, secondary adrenal insufficiency, stroke and spinal cord injury, sympathetic ophthalmia, systemic lupus erythematosus, Syndrome X, tendonitis, thrombocytopenia, tissue rejection, ulcerative colitis, urticaria, uveitis, viral infection, Wegener's granulomatosis or wound healing.
30 . A process for the preparation of a compound of Formula 2
comprising the step of reacting compound of Formula 1
with a base until the reaction is substantially complete, then reacting the anion with acetaldehyde to form a compound of Formula 2
wherein
R′ is alkoxy and
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl;
wherein r is independently 0, 1 or 2.
31 . The process according to claim 30 , further comprising the step of warming.
32 . A process for the preparation of a compound of Formula 3
comprising the step of reacting compound of Formula 2
with a catalyst and hydrogen until the reaction is substantially complete to form a compound of Formula 3
wherein
R′ is alkoxy and
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl;
wherein r is independently 0, 1 or 2.
33 . A process for the preparation of a compound of Formula 4
comprising the step of reacting compound of Formula 3
with a ketone and a base until the reaction is substantially complete to form a compound of Formula 4
wherein
R′ is alkoxy and
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl.
34 . A process for the preparation of a compound of Formula 6
comprising the step of reacting compound of Formula 5
with 1-(bromomethyl)-2-fluoro-4-(trifluoromethyl)benzene until the reaction is substantially complete to form a compound of Formula 6
wherein R″″ is arylhalide.
35 . A process for the preparation of compounds of Formulas 3a and 3b
comprising reacting a compound of Formula 3
with an eneone, a base and a compound of Formula 6
until the reaction is substantially complete to form compounds of Formulas 3a and 3b
wherein
R′ is alkoxy;
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl; and
R″″ is arylhalide.
36 . A process for preparing compounds of Formula 3c and 3d
comprising reacting compounds of Formulas 3a and 3b
with a base until the reaction is substantially complete to form a compound of Formulas 3c and 3d
wherein
R′ is alkoxy and
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl.
37 . A process for preparing a compound of Formula 4a
comprising fractional crystallization of formulas 3c and 3d
until the reaction is substantially complete to form a compound of Formula 4a
wherein
R′ is alkoxy and
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl.
38 . A process for preparing a compound of Formula 7
comprising reacting a compound of Formula 4a
with an acid and methionine until the reaction is substantially complete to form a compound of Formula 7
wherein
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl.
39 . The process according to claim 38 , wherein the acid is methanesulfonic acid.
40 . A process for preparing a compound of Formula 8
comprising reacting a compound of Formula 7
with hydrogen and a catalyst until the reaction is substantially complete to form a compound of Formula 8
wherein
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl.
41 . A process for preparing a compound of Formula 9
comprising reacting a comnound of Formula 8
with a triflating reagent N-phenylbis(trifluoromethanesulfonimide and a base until the reaction is substantially complete to form a compound of Formula 9
wherein
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl.
42 . The process according to claim 41 wherein the triflating reagent is N-phenylbis(trifluoromethanesulfonimide.
43 . A process for preparing a compound of Formula 10
comprising reacting a compound of Formula 9
with carbon monoxide and a catalyst until the reaction is substantially complete to form a compound of Formula 10
wherein
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl and
R′″ is optionally substituted aminoaryl, optionally substituted aminoheterocyclyl, optionally substituted aminoheteroaryl or optionally substituted aminocycloalkyl.
44 . A process for preparing a compound of Formula 11
comprising reacting a compound of Formula 10
with a base until the reaction is substantially complete, then coupling to an amine to form a compound of Formula 11
wherein
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl and
R′″ is optionally substituted aminoaryl, optionally substituted aminoheterocyclyl, optionally substituted aminoheteroaryl or optionally substituted aminocycloalkyl.
45 . A process for preparing a compound of Formula 12
comprising reacting a compound of Formula 11
with a base and trimethylsulfoxonium halide until the reaction is substantially complete to form a compound of Formula 12
wherein
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl and
R′″ is optionally substituted aminoaryl, optionally substituted aminoheterocyclyl, optionally substituted aminoheteroaryl or optionally substituted aminocycloalkyl.
46 . A process for preparing a compound of Formula 13
comprising reacting a compound of Formula 12
with a metal halide until the reaction is substantially complete to form a compound of Formula 13
wherein
R″ is CF 3 , —(CH 2 ) r -optionally substituted aryl, —(CH 2 ) r -optionally substituted (C 3 -C 6 )cycloalkyl, optionally substituted (C 1 -C 3 )alkyl, or —(CH 2 ) r -optionally substituted heteroaryl;
R′″ is optionally substituted aminoaryl, optionally substituted aminoheterocyclyl, optionally substituted aminoheteroaryl or optionally substituted aminocycloalkyl and
R IV is H, optionally substituted (C 1 -C 3 )alkyl, OH or —O-optionally substituted (C 1 -C 3 )alkyl.