Dihydropyrrolopyridine inhibitors of RORγ
Provided are novel compounds of Formula (I): pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by ROR γ . Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I) and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.
1. A method of treating dry eye in a subject, comprising administering to the subject a therapeutically effective amount of a compound having the formula:
or a pharmaceutically acceptable salt thereof.
2. A method of treating dry eye in a subject, comprising administering to the subject a therapeutically effective amount of a compound having the formula:
or a pharmaceutically acceptable salt thereof, wherein
R 2 is (C 1 -C 3 )alkyl, hydroxy(C 1 -C 3 )alkyl, halo(C 1 -C 3 )alkyl, benzyl, (C 1 -C 3 )alkoxy(C 1 -C 3 )alkyl, tetrahydropyranyl, or —CH 2 -tetrahydropyranyl;
R 3 and R 4 are each independently hydrogen or methyl;
Cy 1 is phenyl or pyridyl, each substituted with (C 1 -C 3 )alkylsulfonyl; and
Cy 2 is hydrogen, halo(C 1 -C 3 )alkyl, cyclohexyl, or tetrahydropyranyl, wherein the cyclohexyl and tetrahydropyranyl are each optionally substituted with one or more groups selected from halo(C 1 -C 3 )alkyl and C 1 -C 3 (alkoxy).
3. The method of claim 2 , wherein the compound is of the Formula:
or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the compound is of the Formula:
or a pharmaceutically acceptable salt thereof.
5. The method of claim 4 , wherein the compound is of the Formula:
or a pharmaceutically acceptable salt thereof.
6. The method of claim 5 , wherein Cy 2 is cyclohexyl or tetrahydropyranyl, each of which are optionally substituted with one or more groups selected from halo(C 1 -C 3 )alkyl and C 1 -C 3 (alkoxy).
7. The method of claim 6 , wherein the compound is of the Formula:
or a pharmaceutically acceptable salt thereof, wherein
X is CH or N;
Y 1 is O and Y 2 is CH 2 , Y is CH 2 and Y 2 is O, or Y 1 and Y 2 are each CH 2 ;
R 9 is halo(C 1 -C 3 )alkyl; and
R 10 is (C 1 -C 3 )alkylsulfonyl.
8. The method of claim 7 , wherein the compound is of the Formula:
or a pharmaceutically acceptable salt thereof.
9. The method of claim 8 , wherein the compound is of the Formula:
or a pharmaceutically acceptable salt thereof.
10. The method of claim 9 , wherein R 2 is methyl, ethyl, benzyl, or isopropyl.
11. The method of claim 10 , wherein R 2 is ethyl or isopropyl.
12. The method of claim 11 , wherein R 9 is CF 3 ; and R 10 is SO 2 Et or SO 2 Me.
13. The method of claim 12 , wherein the compound is selected from
or a pharmaceutically acceptable salt thereof.