US2018200247A1PendingUtilityA1
Substituted Tetrahydroquinolinone Compounds as ROR Gamma Modulators
Assignee: AURIGENE DISCOVERY TECH LTDPriority: May 15, 2015Filed: May 13, 2016Published: Jul 19, 2018
Est. expiryMay 15, 2035(~8.8 yrs left)· nominal 20-yr term from priority
C07D 401/14C07D 239/26C07D 401/04C07D 405/04C07D 487/04C07D 409/04C07D 403/04A61K 31/4725A61K 31/4985A61K 31/501A61P 37/00A61K 31/4709A61P 29/00A61K 31/506C07D 471/04C07D 239/84A61P 37/06A61P 25/28A61P 21/04A61P 17/06A61P 11/06A61P 11/00A61P 9/10A61P 9/00A61P 7/04A61P 3/10A61P 1/16A61P 1/00A61P 35/00A61P 19/02A61P 17/00
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Claims
Abstract
The present invention provides substituted tetrahydroquinolinone and related compounds of formula (I), which are therapeutically useful as modulators of Retinoic acid receptor-related orphan receptors (RORs), more particularly as RORγ modulators. These compounds are useful in the treatment and prevention of diseases and/or disorder, in particular their use in diseases and/or disorder mediated by RORγ receptor. The present invention also provides preparation of the compounds and pharmaceutical formulations comprising at least one of the substituted tetrahydroquinolinone or related compounds of formula (I), together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
Claims
exact text as granted — not AI-modified1 . A compound of formula (I):
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein,
ring Het is heterocyclyl;
each Y 1 , Y 2 and Y 3 are independently CR a or N, wherein 0-2 of Y 1 , Y 2 and Y 3 are N;
each Z 1 , Z 2 , Z 3 , Z 4 and Z 5 are independently CR a or N, wherein 0-3 of Z 1 , Z 2 , Z 3 , Z 4 and Z 5 are N;
L is .—NR b —C(O)—(CR b R c ) n —, .—C(O)—NR b —(CR b R c ) n —, .—NR b —S(O) 2 —(CR b R c ) n — or .—S(O) 2 —NR b —(CR b R c ) n —; wherein the group marked with . is connected to the ring containing Y 1 , Y 2 and Y 3 ;
each R 1 , R 2 , R 6 and R 7 are independently hydrogen, halo, alkyl, hydroxy, hydroxyalkyl, cyano, alkoxy, haloalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, —COR d or —COOR d ;
R 3 at each occurrence is independently hydroxy, halo, alkyl, alkylamino, alkoxy, haloalkyl, haloalkoxy or cycloalkyl; alternatively, two R 3 on the same carbon together form an oxo (═O) group;
R 4 is hydrogen, alkyl or alkoxy;
R 5 is alkyl, —(CH 2 ) n NR b R c , hydroxyalkyl, cycloalkyl, aryl or heterocyclyl;
R a is hydrogen, alkyl, alkoxy, halo, cycloalkyl or aryl;
R b and R c are each independently hydrogen, alkyl or alkoxyalkyl;
alternatively, R b and R c on the same atom together form a ring;
R d is hydrogen, alkyl, alkoxy or cycloalkyl;
m is 0 to 3; and
n is0 to 3.
2 . The compound according to claim 1 , is a compound of formula (IA):
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein,
ring Het, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R a , L, Z 1 , Z 2 , Z 3 , Z 4 , Z 5 and m are same as defined in claim 1 .
3 . The compound according to claim 1 , is a compound of formula (IB):
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein,
ring Het, R 1 , R 2 , R 3 , R 4 , R 5 , Y 1 , Y 2 , Y 3 and m are same as defined in claim 1 .
4 . The compound according to claim 1 , is a compound of formula (IC):
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein,
ring Het, R 1 , R 2 , R 3 , R 4 , R 5 , R a and m are same as defined in claim 1 .
5 . The compound according to claim 1 , is a compound of formula (ID):
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein,
L, R 1 , R 2 , R 3 , R 4 , R 5 , Y 1 , Y 2 , Y 3 , Z 1 , Z 2 , Z 3 , Z 4 , Z 5 and m are same as defined in claim 1 .
6 . The compound according to claim 1 , is a compound of formula (IE):
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein,
L, R 1 , R 2 , R 3 , R 4 , R 5 , Z 1 , Z 2 , Z 3 , Z 4 , Z 5 and m are same as defined in claim 1 .
7 . The compound according to claim 1 , is a compound of formula (IF):
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein,
L, R 1 , R 2 , R 3 , R 4 , R 5 , Y 1 , Y 2 , Y 3 , Z 1 , Z 2 , Z 3 , Z 4 , Z 5 and m are same as defined in claim 1 .
8 . The compound according to claim 1 , is a compound of formula (IG):
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein,
L, R 1 , R 2 , R 3 , R 4 , R 5 , Y 1 , Y 2 , Y 3 , Z 1 , Z 2 , Z 3 , Z 4 and Z 5 are same as defined in claim 1 .
9 . The compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein ring Het is pyridyl, pyridazinyl, pyridazinone, pyrimidinyl, pyrazinyl, pyrazolyl, imidazopyrazinyl, imidazopyridyl, pyrrolopyrazinyl, thienyl, benzodioxolyl, benzimidazolyl, imidazolyl, imidazopyridazinyl or tetrahydroisoquinolinonyl.
10 . The compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof wherein,
11 . The compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof wherein
12 . The compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof wherein L is .—NHCOCH 2 — or .—CONHCH 2 — wherein the group marked with . is connected to the ring containing Y 1, Y 2 and Y 3 .
13 . The compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof wherein each R 1 , R 2 , R 6 and R 7 are hydrogen; R 4 is alkyl.
14 . The compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof wherein R 5 is alkyl.
15 . The compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof wherein R a is hydrogen or alkyl.
16 . A compound that is selected from the group consisting of:
Compound
No.
IUPAC Name
1
N-(4,6-dimethyl-5-oxo-6-(pyridin-2-yl)-5,6,7,8-tetrahydroquinolin-2-yl)-2-(4-
(ethylsulfonyl)phenyl)acetamide;
2
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridin-3-yl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
3
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(6-(trifluoromethyl)pyridin-
3-yl)-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
4
2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyridin-2-yl)-7,7-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
5
2-(4-(ethylsulfonyl)phenyl)-N-(6-(4-methoxypyridin-2-yl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
6
2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-a]pyrazin-8-yl)-6-methyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
7
N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
8
N-(6-methyl-5-oxo-6-(5-(trifluoromethyl)pyridin-2-yl)-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;
9
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(2-methylimidazo[1,2-a]pyrazin-
8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
10
N-(6-(5-chloropyridin-2-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-
2-(4-(methylsulfonyl)phenyl)acetamide;
11
2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-a]pyrazin-8-yl)-3,6-dimethyl-
5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
12
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridazin-3-yl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
13
N-(6-(imidazo[1,2-a]pyridin-8-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;
14
N-(6-ethyl-6-(imidazo[1,2-a]pyrazin-8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-
2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
15
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(pyrrolo[1,2-a]pyrazin-1-
yl)-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
16
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(6-methylimidazo[1,2-a]pyrazin-
8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
17
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridin-3-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
18
N-(4,6-dimethyl-5-oxo-6-(pyridin-3-yl)-5,6,7,8-tetrahydroquinolin-2-yl)-2-(4-
(ethylsulfonyl)phenyl)acetamide;
19
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
20
2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyridin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
21
2-(4-(ethylsulfonyl)phenyl)-N-(6-(4-methoxypyrimidin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
22
2-(4-(ethylsulfonyl)phenyl)-N-(6-(4-methoxypyridin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
23
2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-fluoropyridin-2-yl)-4,6-dimethyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
24
N-(6-(5-chloro-3-methoxypyridin-2-yl)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
25
2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-methoxypyrimidin-5-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
26
2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-a]pyrazin-8-yl)-4,6-dimethyl-
5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
27
2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyrazin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
28
N-(6-(2,6-dimethylpyrimidin-4-yl)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
29
N-(6-(4,6-dimethylpyrimidin-2-yl)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
30
2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-methoxypyrimidin-4-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
31
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridazin-3-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
32
N-(4,6-dimethyl-5-oxo-6-(5-(trifluoromethyl)pyridin-2-yl)-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;
33
N-(6-(imidazo[1,2-a]pyrazin-8-yl)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;
34
N-(4,6-dimethyl-6-(6-methylpyridazin-3-yl)-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
35
N-(6-(6-methoxypyridazin-3-yl)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;
36
2-(4-(ethylsulfonyl)phenyl)-N-(6-(4-hydroxypyrimidin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
37
2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-hydroxypyridin-4-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
38
N-(6-(5-chloro-3-hydroxypyridin-2-yl)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
39
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-hydroxypyridin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
40
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-hydroxypyridin-3-yl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
41
N-(6-(6-ethylpyridazin-3-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-
yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
42
N-(6-(benzo[d][1,3]dioxol-5-yl)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
43
N-(4,6-dimethyl-6-(1-methyl-1H-benzo[d]imidazol-5-yl)-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
44
N-(4,6-dimethyl-6-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
45
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(5-methylthiophen-2-yl)-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
46
N-(6-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
47
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(1H-pyrazol-1-yl)-5,6,7,8-
tetrahydroquinolin-2-yl)acetamide;
48
2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-a]pyrazin-8-yl)-6,8-dimethyl-
5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
49
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(3-methylimidazo[1,2-a]pyrazin-
8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
50
2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-isopropylpyrimidin-4-yl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
51
N-(6-(2,6-dimethylimidazo[1,2-a]pyrazin-8-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
52
N-(4,6-dimethyl-6-(2-methylimidazo[1,2-a]pyrazin-8-yl)-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
53
N-(4,6-dimethyl-5-oxo-6-(6-(trifluoromethyl)pyridazin-3-yl)-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
54
2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-a]pyrazin-8-yl)-7-methyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
55
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(6-
(trifluoromethyl)pyridazin-3-yl)-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
56
2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyrimidin-2-yl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
57
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-isopropoxypyridazin-3-yl)-6-methyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
58
2-(4-(ethylsulfonyl)-2-fluorophenyl)-N-(6-methyl-6-(2-methylimidazo[1,2-
a]pyrazin-8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
59
N-(6-methyl-6-(2-methylimidazo[1,2-a]pyrazin-8-yl)-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;
60
2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-isopropylpyrazin-2-yl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
61
2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyrimidin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
62
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-isopropylpyridazin-3-yl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
63
N-(6-(6-ethylpyridazin-3-yl)-4,6-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-
2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
64
2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-methoxy-6-methylpyrimidin-4-yl)-6-
methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
65
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxy-2-methylpyrimidin-4-yl)-6-
methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
66
2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-fluoro-2-methylimidazo[1,2-a]pyrazin-8-
yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
67
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(2-methyl-6-(trifluoromethyl)-
pyrimidin-4-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
68
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(5-methylimidazo[1,2-a]pyrazin-
8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
69
N-(6-(2,6-dimethylpyrimidin-4-yl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
70
N-(4,6-dimethyl-6-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
71
N-(6-(3-cyclopropylimidazo[1,2-a]pyrazin-8-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
72
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(2-(trifluoromethyl)-
imidazo[1,2-a]pyrazin-8-yl)-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
73
2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyridazin-3-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
74
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(3-(trifluoromethyl)-
imidazo[1,2-a]pyrazin-8-yl)-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
75
N-(4,6-dimethyl-6-(2-methylimidazo[1,2-b]pyridazin-6-yl)-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
76
N-(6-(5-cyclopropyl-6-methoxypyridazin-3-yl)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
77
2-(4-(ethylsulfonyl)phenyl)-N-(6-(imidazo[1,2-b]pyridazin-6-yl)-4,6-
dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
78
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(6-methyl-2-(trifluoromethyl)-
pyrimidin-4-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
79
N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(5-(ethylsulfonyl)pyridin-2-yl)acetamide;
80
2-(5-(ethylsulfonyl)pyridin-2-yl)-N-(6-(6-methoxypyridazin-3-yl)-4,6-
dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
81
N-(6-(2,6-dimethylpyrimidin-4-yl)-6,7-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
82
N-(6-(2,6-dimethylpyrimidin-4-yl)-7-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
83
N-(7-(2,6-dimethylpyrimidin-4-yl)-7-methyl-8-oxo-5,6,7,8-
tetrahydroisoquinolin-3-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
84
2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-hydroxypyridin-3-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
85
2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-hydroxypyridin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
86
2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-hydroxy-4-methylpyridin-3-yl)-4,6-
dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
87
2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-hydroxypyridin-2-yl)-7,7-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
88
2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-hydroxypyridin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
89
N-(6-(3-hydroxypyridin-2-yl)-4,6-dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-
2-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;
90
2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-hydroxypyridin-2-yl)-7,7-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
91
2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-hydroxypyridin-2-yl)-7-methyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
92
N-(6-(5-chloroimidazo[1,2-a]pyrazin-8-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
93
N-(6-(6-chloropyridazin-3-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-
yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
94
3-(2-(2-(4-(ethylsulfonyl)phenyl)acetamido)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-6-yl)-6-methoxypyridazine 1-oxide;
95
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxy-4-methylpyridazin-3-yl)-4,6-
dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
96
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxy-5-methylpyridazin-3-yl)-4,6-
dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
97
2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-fluoroimidazo[1,2-a]pyrazin-8-yl)-6-
methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
98
N-(6-(6-(dimethylamino)pyridazin-3-yl)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
99
6-(2,6-dimethylpyrimidin-4-yl)-N-(4-(ethylsulfonyl)benzyl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinoline-2-carboxamide;
100
N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydronaphthalen-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
101
2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-hydroxypyridin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of Compound-
84);
102
2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-hydroxypyridin-2-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of Compound-
84);
103
N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide; (Isomer-1 of
Compound-7);
104
N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide; (Isomer-2 of
Compound-7);
105
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(2-methylimidazo[1,2-a]pyrazin-
8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of
Compound-9);
106
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(2-methylimidazo[1,2-a]pyrazin-
8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of
Compound-9);
107
N-(6-(2,6-dimethylpyrimidin-4-yl)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide; (Isomer-1 of
Compound-28);
108
N-(6-(2,6-dimethylpyrimidin-4-yl)-4,6-dimethyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide; (Isomer-2 of
Compound-28);
109
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridazin-3-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of Compound-
31);
110
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxypyridazin-3-yl)-4,6-dimethyl-5-
oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of Compound-
31);
111
2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyrimidin-2-yl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of Compound-56);
112
2-(4-(ethylsulfonyl)phenyl)-N-(6-(5-methoxypyrimidin-2-yl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of Compound-56);
113
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(3-methylimidazo[1,2-a]pyrazin-
8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of
Compound-49);
114
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(3-methylimidazo[1,2-a]pyrazin-
8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of
Compound-49);
115
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxy-2-methylpyrimidin-4-yl)-6-
methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of
Compound-65);
116
2-(4-(ethylsulfonyl)phenyl)-N-(6-(6-methoxy-2-methylpyrimidin-4-yl)-6-
methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of
Compound-65);
117
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(6-methylimidazo[1,2-a]pyrazin-
8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of
Compound-16);
118
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(6-methylimidazo[1,2-a]pyrazin-
8-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of
Compound-16);
119
2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-methoxy-6-methylpyrimidin-4-yl)-6-
methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-1 of
Compound-64);
120
2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-methoxy-6-methylpyrimidin-4-yl)-6-
methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide; (Isomer-2 of
Compound-64);
121
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(3-
(trifluoromethyl)imidazo[1,2-a]pyrazin-8-yl)-5,6,7,8-tetrahydroquinolin-2-
yl)acetamide; (Isomer-1 of Compound-74);
122
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-5-oxo-6-(3-
(trifluoromethyl)imidazo[1,2-a]pyrazin-8-yl)-5,6,7,8-tetrahydroquinolin-2-
yl)acetamide; (Isomer-2 of Compound-74);
123
N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(5-(ethylsulfonyl)pyridin-2-yl)acetamide; (Isomer-
1 of Compound-79);
124
N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(5-(ethylsulfonyl)pyridin-2-yl)acetamide; (Isomer-
2 of Compound-79);
125
6-(2,6-dimethylpyrimidin-4-yl)-N-(4-(ethylsulfonyl)benzyl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinoline-2-carboxamide; (Isomer-1 of Compound-99);
126
6-(2,6-dimethylpyrimidin-4-yl)-N-(4-(ethylsulfonyl)benzyl)-6-methyl-5-oxo-
5,6,7,8-tetrahydroquinoline-2-carboxamide; (Isomer-2 of Compound-99);
127
N-(7-(2,6-dimethylpyrimidin-4-yl)-7-methyl-8-oxo-5,6,7,8-
tetrahydroisoquinolin-3-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide; (Isomer-1
of Compound-83);
128
N-(7-(2,6-dimethylpyrimidin-4-yl)-7-methyl-8-oxo-5,6,7,8-
tetrahydroisoquinolin-3-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide; (Isomer-2
of Compound-83);
129
2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-fluoro-2-methylimidazo[1,2-a]pyrazin-8-
yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
130
2-(4-(ethylsulfonyl)phenyl)-N-(6-(3-fluoro-2-methylimidazo[1,2-a]pyrazin-8-
yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
131
N-(6-(6-ethyl-2-methylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
132
N-(6-(2-ethyl-6-methylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
133
N-(6-(2,6-diethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-tetrahydroquinolin-
2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
134
7-(2,6-dimethylpyrimidin-4-yl)-N-(4-(ethylsulfonyl)benzyl)-7-methyl-8-oxo-
5,6,7,8-tetrahydroisoquinoline-3-carboxamide;
135
2-(4-(ethylsulfonyl)phenyl)-N-(6-(2-methoxy-6-methylpyrimidin-4-yl)-4,6-
dimethyl-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
136
N-(7-(2,6-dimethylpyrimidin-4-yl)-7-methyl-8-oxo-5,6,7,8-
tetrahydroquinolin-3-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
137
N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinazolin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
138
N-(6-(2,6-dimethylpyrimidin-4-yl)-6-methyl-5-oxo-5,6,7,8-
tetrahydroquinoxalin-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
139
2-(4-(ethylsulfonyl)phenyl)-N-(6-methyl-6-(2-methyl-6-(trifluoromethoxy)-
pyrimidin-4-yl)-5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)acetamide;
140
6-(2,6-dimethylpyrimidin-4-yl)-N-(4-(ethylsulfonyl)benzyl)-7-isopropyl-5-
oxo-5,6,7,8-tetrahydroquinoline-2-carboxamide;
141
6-(2,6-dimethylpyrimidin-4-yl)-N-(4-(ethylsulfonyl)benzyl)-8-isopropyl-5-
oxo-5,6,7,8-tetrahydroquinoline-2-carboxamide; and
142
6-(2,6-dimethylpyrimidin-4-yl)-N-(4-(ethylsulfonyl)benzyl)-7-isopropyl-6-
methyl-5-oxo-5,6,7,8-tetrahydroquinoline-2-carboxamide;
or a pharmaceutically acceptable salt or a stereoisomer thereof.
17 . A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof and at least one pharmaceutically acceptable carrier or excipient.
18 . (canceled)
19 . A method of modulating the function of RORγ in a subject in need thereof by administering to a subject a therapeutically effective amount of the compound of claim 1 .
20 . A method of treating a disorder or disease mediated by RORγ in a subject in need thereof comprising administering to the subject a compound of claim 1 .
21 . The method of claim 20 , wherein the disorder or disease mediated by RORγ is an immune disorder or an inflammatory disease.
22 . The method according to claim 21 , wherein the disease or disorder is rheumatoid arthritis, psoriasis, chronic graft-versus-host disease, acute graft-versus-host disease, Crohn's disease, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, Celiac Sprue, idiopathic thrombocytopenic thrombotic purpura, myasthenia gravis, Sjogren's syndrome, asthma, epidermal hyperplasia, scleroderma or ulcerative colitis.
23 . The method according to claim 21 , wherein the disease or disorder is cartilage inflammation, bone degradation, arthritis, juvenile arthritis, juvenile rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, polyarticular juvenile rheumatoid arthritis, systemic onset juvenile rheumatoid arthritis, juvenile ankylosing spondylitis, juvenile enteropathic arthritis, juvenile reactive arthritis, juvenile Reter's Syndrome, SEA Syndrome, juvenile dermatomyositis, juvenile psoriatic arthritis, juvenile scleroderma, juvenile systemic lupus erythematosus, juvenile vasculitis, pauciarticular rheumatoid arthritis, polyarticular rheumatoid arthritis, systemic onset rheumatoid arthritis, ankylosing spondylitis, enteropathic arthritis, reactive arthritis, Reter's Syndrome, dermatomyositis, psoriatic arthritis, vasculitis, myolitis, polymyolitis, dermatomyolitis, osteoarthritis, polyarteritis nodossa, Wegener's granulomatosis, arteritis, polymyalgia rheumatica, sarcoidosis, sclerosis, primary biliary sclerosis, sclerosing cholangitis, dermatitis, atopic dermatitis, atherosclerosis, Still's disease, chronic obstructive pulmonary disease, Guillain-Barre disease, Type I diabetes mellitus, Graves' disease, Addison's disease, Raynaud's phenomenon, autoimmune hepatitis, psoriatic epidermal hyperplasia, plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis or an immune disorder associated with or arising from activity of pathogenic lymphocytes.
24 . The method of claim 19 , further comprising conjointly administering to the subject a second therapeutic agent.
25 . A method of reducing an amount of IL-17 and other effector cytokines of Th17 cells in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .
26 . The method of claim 19 , wherein the subject is a human or other mammal.
27 . (canceled)
28 . (canceled)Cited by (0)
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