Thiazolopyrrolidine inhibitors of ROR- γ

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

Z is —C(O)NR 1 —, —NR 1 C(O)—, —NR 1 —, or NR 1 SO 2 ;

R 1 is hydrogen or (C 1 -C 3 )alkyl;

L 1 and L 2 are each independently a bond or (C 1 -C 3 )alkylene optionally substituted with (C 1 -C 2 )alkyl or spirocyclopropane;

R 2 is (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, phenyl, benzyl, heteroaryl, monocyclic cycloalkyl or monocyclic heterocyclyl, each optionally substituted with 1 to 2 groups independently selected from CN, halo, hydroxyl, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, oxo, and halo(C 1 -C 6 )alkoxy;

R 3 is hydrogen or (C 1 -C 3 )alkyl;

Cy 1 is aryl or heteroaryl, each of which is optionally substituted with 1 to 3 groups independently selected from R 5 ;

R 4 is hydrogen or (C 1 -C 3 )alkyl; and

Cy 2 is aryl, heteroaryl, monocyclic cycloalkyl, or monocyclic heterocyclyl, wherein the aryl and heteroaryl are each optionally fused with a monocyclic heterocyclyl or monocyclic cycloalkyl, and wherein Cy 2 is optionally substituted with 1 to 3 groups independently selected from R 6 ; and

R 5 and R 6 are each independently selected from halo, cyano, nitro, amino, hydroxy, carboxy, (C 1 -C 6 )alkyl, heterocyclyl, hydroxy(C 1 -C 6 )alkyl, CO 2 H, (CH 2 ) 1-3 COOH, (C 3 -C 6 )cycloalkyl, hydroxy(C 3 -C 6 )cycloalkyl, (C 4 -C 7 )cycloalkylalkyl, (C 2 -C 6 )alkenyl, halo(C 2 -C 6 )alkenyl, hydroxy(C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl(C 2 -C 4 )alkynyl, halo(C 1 -C 6 )alkyl, halo(C 3 -C 6 )cycloalkyl, halo(C 4 -C 7 )cycloalkylalkyl, (C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkoxy, (C 4 -C 7 )cycloalkylalkoxy, halo(C 1 -C 6 )alkoxy, halo(C 3 -C 6 )cycloalkoxy, halo(C 4 -C 7 )cycloalkylalkoxy, (C 1 -C 6 )alkylthio, (C 3 -C 6 )cycloalkythio, (C 4 -C 7 )cycloalkylalkylthio, halo(C 1 -C 6 )alkylthio, halo(C 3 -C 6 )cycloalkythio, halo(C 4 -C 7 )cycloalkylalkylthio, (C 1 -C 6 )alkylsulfonyl, (C 3 -C 6 )cycloalkylsulfinyl, (C 4 -C 7 )cycloalkylalkylsulfinyl, halo(C 1 -C 6 )alkylsulfonyl, halo(C 3 -C 6 )cycloalkylsulfinyl, halo(C 4 -C 7 )cycloalkylalkylsulfinyl, (C 1 -C 6 )alkylsulfonyl, (C 3 -C 6 )cycloalkylsulfonyl, (C 4 -C 7 )cycloalkylalkylsulfonyl, halo(C 1 -C 6 )alkylsulfonyl, halo(C 3 -C 6 )cycloalkylsulfonyl, halo(C 4 -C 7 )cycloalkylalkylsulfonyl, (C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy(C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, H 2 NCO, H 2 NSO 2 , (C 1 -C 6 )alkylaminocarbonyl, di(C 1 -C 6 )alkylaminocarbonyl, (C 1 -C 3 )alkoxy(C 1 -C 3 )alkylaminocarbonyl, heterocyclylcarbonyl, (C 1 -C 6 )alkylaminosulfonyl, di(C 1 -C 6 )alkylaminosulfonyl, heterocyclylsulfonyl, (C 1 -C 6 )alkylcarbonylamino, (C 1 -C 6 )alkylcarbonylamino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfonylamino, (C 1 -C 6 )alkylsulfonylamino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkoxy, aryl, heteroaryl, oxo, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl amino(C 2 -C 6 )alkoxy, (C 1 -C 6 )alkylamino(C 2 -C 6 )alkoxy, di(C 1 -C 6 )alkylamino(C 2 -C 6 )alkoxy, (C 1 -C 6 )alkylcarbonyl, (C 3 -C 6 )cycloalkylcarbonyl, (C 3 -C 6 )cycloalkylaminocarbonyl, {(C 3 -C 6 )cycloalkyl}{(C 1 -C 6 )alkyl}aminocarbonyl, di(C 3 -C 6 )cycloalkylaminocarbonyl, (C 3 -C 6 )cycloalkylaminosulfonyl, {(C 3 -C 6 )cycloalkyl}{(C 1 -C 6 )alkyl}aminosulfonyl, di(C 3 -C 6 )cycloalkylaminosulfonyl, cyano(C 1 -C 6 )alkyl, aminocarbonyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylaminocarbonyl(C 1 -C 6 )alkyl, di(C 1 -C 6 )alkylaminocarbonyl(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkylaminocarbonyl(C 1 -C 6 )alkyl, {(C 3 -C 6 )cycloalkyl}{(C 1 -C 6 )alkyl}aminocarbonyl(C 1 -C 6 )alkyl and di(C 3 -C 6 )cycloalkylaminocarbonyl(C 1 -C 6 )alkyl.

2. The compound of claim 1 , wherein the compound is of Formula (Ia):

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 2 , wherein the compound is of Formula (Ib):

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 3 , wherein the compound is of Formula (Ib′):

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 4 , wherein Cy 1 is phenyl, pyridinyl, or pyrimidinyl, each of which is optionally substituted with 1 to 3 groups independently selected from R 5 .

6. The compound of claim 5 , wherein Cy 2 is phenyl, pyridinyl, pyrimidinyl, cyclohexyl, or oxadiazolyl, each of which are optionally substituted with 1 to 3 groups independently selected from R 6 .

7. The compound of claim 6 , wherein R 5 is selected from halo, cyano, (C 1 -C 3 )alkyl, halo(C 1 -C 3 )alkyl, hydroxy(C 1 -C 3 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, CO 2 H, (CH 2 ) 1-3 COOH, and (C 1 -C 3 )alkylsulfonyl.

8. The compound of claim 7 , wherein R 2 is isopropyl, isobutyl, sec-butyl, phenyl, benzyl, cyclopropyl, tetrahydrofuranyl, or tetrahydropyranyl, wherein the phenyl and benzyl are each optionally substituted with 1 to 2 groups independently selected from CN, halo, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and halo(C 1 -C 6 )alkoxy.

9. The compound of claim 8 , wherein:

Cy 1 is phenyl, 2-pyridinyl, or 2-pyrimidinyl, each of which is optionally substituted with 1 to 2 groups independently selected from halo, (C 1 -C 3 )alkyl, (CH 2 ) 1-3 COOH, (C 1 -C 3 )alkylsulfonyl, cyano, or hydroxy(C 1 -C 3 )alkyl; and

R 2 is isopropyl, isobutyl, sec-butyl, phenyl, benzyl, or cyclopropyl, wherein the phenyl and benzyl are each optionally substituted with 1 to 2 groups independently selected from CN, halo, (C 1 -C 3 )alkyl, and (C 1 -C 3 )alkoxy.

10. The compound of claim 9 , wherein:

Cy 1 is phenyl optionally substituted with 1 to 2 groups independently selected from halo, (C 1 -C 3 )alkyl, CH 2 COOH, (C 1 -C 3 )alkanesulfonyl, cyano, or hydroxy(C 1 -C 3 )alkyl; and

R 2 is isopropyl, isobutyl, sec-butyl, phenyl, benzyl, or cyclopropyl, wherein the phenyl and benzyl are each optionally substituted with 1 to 2 groups independently selected from CN, halo, (C 1 -C 3 )alkyl, and (C 1 -C 3 )alkoxy.

11. The compound of claim 10 , wherein the compound is of Formula (Ic):

or a pharmaceutically acceptable salt thereof, wherein:

each Y is independently CH, CR 5 , or N; and

R 7 is (C 1 -C 3 )alkyl.

12. The compound of claim 11 , wherein the compound is of Formula (Id):

or a pharmaceutically acceptable salt thereof, wherein:

each X is independently CH, CR 6 , or N;

each Y is independently CH, CR 5 , or N;

n is 0, 1, or 2; and

R 7 is (C 1 -C 3 )alkyl.

13. The compound of claim 12 , wherein R 2 is isopropyl, cyclopropyl, isobutyl or sec-butyl.

14. The compound of claim 13 , wherein R 2 is isopropyl.

15. The compound of claim 14 , wherein R 6 is selected from halo, cyano, nitro, amino, hydroxy, carboxy, (C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, H 2 NCO, (C 2 -C 6 )alkenyl, halo(C 2 -C 6 )alkenyl, hydroxy(C 2 -C 6 )alkenyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylsulfinyl, halo(C 1 -C 6 )alkylsulfinyl (C 1 -C 6 )alkylsulfonyl, halo(C 1 -C 6 )alkylsulfonyl, oxo, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylcarbonyl, and aminocarbonyl(C 1 -C 6 )alkyl.

16. The compound of claim 15 , wherein R 6 is selected from halo, cyano, nitro, amino, hydroxy, carboxy, (C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and halo(C 1 -C 6 )alkoxy.

17. The compound of claim 16 , wherein R 6 is halo, cyano, halo(C 1 -C 3 )alkyl, or halo(C 1 -C 3 )alkoxy.

18. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

19. A method of treating one or more diseases or disorders selected from ankylosing spondylitis, psoriasis and psoriatic arthritis (PsA).