Bicyclic amide compounds and methods of use thereof

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein

R 1 and R 2 :

(a) are each independently selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 thioalkyl, C 1 -C 6 alkyl-N(R N ) 2 , phenyl, 5 to 6 membered heteroaryl, and 4 to 5 membered heterocyclyl;

(b) together with the adjacent amide N, form a 4 to 7 membered unsaturated heterocyclic ring optionally substituted by one or two R 3 , wherein the unsaturated heterocyclic ring contains zero or one additional heteroatom selected from the group consisting of NR N , O and S; or

(c) together with the adjacent amide N, form a bicyclic heteroaryl moiety optionally substituted by one or two R 3 , wherein the bicyclic heterocyclic moiety contains zero to three additional heteroatoms selected from the group consisting of N, O and S, wherein only one of the additional heteroatoms is O or S;

each R 3 is independently selected from the group consisting of F, Cl, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 hydroxyalkyl, and phenoxy; or, when R 1 and R 2 together with the adjacent amide N form a 6 membered ring, two R 3 may together form a 1 to 2 carbon bridge or a C 3 -C 5 spirocycloalkyl;

each R N is independently selected from the group consisting of H, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy and C 1 -C 6 haloalkyl; or two R N may together with the adjacent N form a 4-6 membered ring;

wherein

 is selected from the group consisting of:

wherein

R 4 is selected from the group consisting of phenyl and 5 to 6 membered heteroaryl, wherein the heteroaryl has one or two heteroatoms selected from O, S and N, and phenyl may be substituted by 1 to 3 substituents selected from the group consisting of halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, and cyano;

each R 5a and R 5b is independently selected from the group consisting of H, F, Cl, C 1 -C 6 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy; and

each R 8 is independently selected from the group consisting of H, halo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and C 1 -C 4 haloalkoxy.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 together with the adjacent amide N, form a 4 to 6 membered unsaturated heterocyclic ring optionally substituted by one or two R 3 , containing zero or one additional heteroatom selected from the group consisting of O and S.

3. The compound of claim 1 having Formula (Ia):

or a pharmaceutically acceptable salt thereof, wherein m is 0, 1 or 2; and n is 1, 2 or 3.

4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein n is 1.

5. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein each R 3 is selected from the group consisting of methyl, ethyl, F and Cl.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein each R 3 is methyl or F.

7. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein

is selected from the group consisting of:

8. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein

is selected from the group consisting of:

9. The compound of claim 1 having Formula (Ib) or (Ic):

or a pharmaceutically acceptable salt thereof, wherein, in each instance,

the C ring is phenyl or a 5 to 6 membered heteroaryl ring;

Z is C or N;

each R 3 is independently selected from the group consisting of F, Cl, C 1 -C 3 alkyl, C 3 -C 5 cycloalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, and C 1 -C 3 haloalkoxy;

n is 1 or 2; and

m is 0, 1 or 2.

10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein

are selected from the group consisting of:

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of C 1 -C 3 alkyl, C 3 -C 5 cycloalkyl, and C 1 -C 3 haloalkyl; and R 2 is selected from the group consisting of C 1 -C 3 alkyl, C 3 -C 5 cycloalkyl, C 1 -C 4 alkoxy, phenyl, and 4 to 5 membered heterocyclyl.

12. The compound of claim 11 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of methyl, cyclopropyl, —CH 2 CF 2 H and —CH 2 CF 3 ; and R 2 is selected from the group consisting of methyl, cyclopropyl, —CH 2 CH 2 OCH 3 , phenyl, and oxetan-3-yl.

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

is selected from the group consisting of:

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

is selected from the group consisting of:

15. A compound, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

16. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

17. A pharmaceutical composition comprising a compound of claim 15 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.