Substituted nicotinimide inhibitors of BTK and their preparation and use in the treatment of cancer, inflammation and autoimmune disease
Compounds of Formula I, as shown below and defined herein: and pharmaceutically acceptable salts, syntheses, intermediates, formulations, and methods of treating diseases including cancer, inflammation, and autoimmune disease mediated at least in part by Bruton's Tyrosine Kinase (BTK).
1. A compound having a Formula IId′, or a pharmaceutically acceptable salt or solvate thereof:
wherein X is
Z is CH or N;
G 1 , G 2 , and G 3 are H, or optionally substituted with one or more substituents independently selected from the group consisting of D (deuterium), C 1-12 alkyl, halogen, CN, and CF 3 ;
R 2 and R 3 are each independently selected from the group consisting of H, D, C 1-12 alkyl, halogen, CN, and CF 3 , wherein C 1-12 alkyl is optionally substituted with NR 11 R 12 ;
R 4 is selected from the group consisting of H, D, C 1-12 alkyl, halogen, CN, and CF 3 ; and
R 11 and R 12 are independently H or C 1-6 alkyl.
2. The compound according to claim 1 , wherein
wherein X is
3. The compound according to claim 1 , wherein G 1 , G 2 , and G 3 are H, or optionally substituted with one or more halogen.
4. The compound according to claim 1 , wherein R 2 and R 3 are H or C 1-12 alkyl, wherein C 1-12 alkyl is optionally substituted with NR 11 R 12 , and R 11 and R 12 are H or CH 3 .
5. The compound according to claim 1 , which is
6. The compound according to claim 1 , which is
7. The compound according to claim 1 , which is
8. The compound according to claim 1 , which is