Sulfonamide-substituted indole modulators of RORC2 and methods of use thereof
The present invention provides sulfonamide-substituted indoles and Methods of Use Thereof-substituted pyrrolopyridines, pharmaceutical compositions thereof methods of modulating RORy activity and/or reducing the amount of IL-17 in a subject, and methods of treating various medical disorders using such indoles and pharmaceutical compositions thereof.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein,
X is phenyl or 5-membered heteroaryl, in each case optionally substituted with one, two, three, four or five substituents independently selected from the group consisting of —CH 3 , —CF 3 , —CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 OH, —OCH 2 CH 2 OCH 3 ,
—F, —Cl, —Br and —CN;
R 1 is —CH 3 or —CH 2 CH 3 ;
W is
optionally substituted with one, two, three, four or five —CH 3 ; and
R 2 is (C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, phenyl or isothiazolyl, optionally substituted with one, two, three, four or five substitutents independently selected for each occurrence from the group consisting of —F, —Cl, —Br, —OH, (C 1 -C 3 )alkyl, (C 1 -C 3 )haloalkyl and (C 3 -C 10 )cycloalkyl.
2. The compound of claim 1 , wherein R 1 is —CH 3 .
3. The compound of claim 2 , wherein W is
4. The compound of claim 2 , wherein W is
5. The compound of claim 2 , wherein W is
6. The compound of claim 5 , wherein X is phenyl substituted with one, two, three, four or five substituents independently selected from the group consisting of —CH 3 , —CF 3 , —CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 OH, —OCH 2 CH 2 OCH 3 ,
—F, —Cl, —Br and —CN.
7. The compound of claim 5 , wherein X is 5-membered heteroaryl optionally substituted with one additional substituent selected from the group consisting of —CH 3 , —CF 3 , —CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 OH, —OCH 2 CH 2 OCH 3 ,
—F, —Cl, —Br and —CN.
8. The compound of claim 5 , wherein X is
9. The compound of claim 8 , wherein R 2 is (C 1 -C 6 )alkyl.
10. The compound of claim 8 , wherein R 2 is unsubstituted (C 3 -C 10 )cycloalkyl.
11. The compound of claim 8 , wherein R 2 is
12. The compound of claim 1 , selected from the group consisting of
and pharmaceutically acceptable salts thereof.
13. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, admixed with a pharmaceutically acceptable carrier, excipient or dilutant.