Fused imidazole derivatives as IDO/TDO inhibitors
The present application relates to compounds and methods for the modulation (e.g., inhibition) of the enzyme indoleamine 2,3-dioxygenase and/or tryptophan 2,3-dioxygenase (IDO/TDO), and methods of treating diseases and disorders in which IDO/TDO plays a role. The present application provides compounds of Formula (I) or (II):
1. A compound of Formula (I)
or a pharmaceutically acceptable salt or solvate thereof, wherein:
W 1 is CR 1 or N;
W 2 is CR 2 or N;
W 3 is CR 3 or N;
W 4 is CR 4 or N;
R 1 , R 2 , R 3 , and R 4 are each independently H, OH, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy;
Z 1 , Z 2 , and Z 3 are each independently a single bond, CHR Z , or CH 2 CHR Z , wherein one of Z 1 , Z 2 , and Z 3 is CHR Z , or one of Z 1 , Z 2 , and Z 3 is CH 2 CHR Z ;
each R Z is independently H, OH, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy;
Y is H, C 1 -C 4 alkyl, or C 1 -C 4 haloalkyl;
n is 0, 1, 2, or 3;
R 5 is OH, halogen, C 1 -C 4 alkoxy, or C 1 -C 4 haloalkoxy;
R 6 is H, OH, halogen, C 1 -C 4 alkoxy, or C 1 -C 4 haloalkoxy; and
R 7 and R 8 are each independently H, halogen, C 1 -C 4 alkyl, or C 1 -C 4 haloalkyl.
2. The compound of claim 1 , wherein W 1 is CR 1 , W 2 is CR 2 , W 3 is CR 3 , W 4 is CR 4 , and R 1 , R 2 , R 3 , and R 4 are each H.
3. The compound of claim 1 , wherein W 1 is CR 1 , W 2 is CR 2 , W 3 is CR 3 , W 4 is CR 4 , and at least one of R 1 , R 2 , R 3 , and R 4 is OH, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy.
4. The compound of claim 1 , wherein one of W 1 , W 2 , W 3 , and W 4 is N.
5. The compound of claim 1 , wherein one of Z 1 , Z 2 , and Z 3 is CH 2 CHR Z .
6. The compound of claim 1 , wherein one of Z 1 , Z 2 , and Z 3 is CHR Z .
7. The compound of claim 1 , wherein R Z is H.
8. The compound of claim 1 , wherein R Z is OH, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy.
9. The compound of claim 1 , wherein n is 0.
10. The compound of claim 1 , wherein n is 1.
11. The compound of claim 1 , wherein R 5 is OH.
12. The compound of claim 1 , wherein R 5 is halogen.
13. The compound of claim 1 , wherein the compound is of Formula (Ib), (Ic), or (Id)
or a pharmaceutically acceptable salt or solvate thereof.
14. The compound of claim 1 , selected from
wherein Cy represents cyclohexyl.
15. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier or excipient.