Heterocycle comprising tyrosine kinase inhibitors
The present disclosure provides compounds of formula (I) that are tyrosine kinase inhibitors, in particular Bruton tyrosine kinase (“BTK”) inhibitors, and are therefore useful for the treatment of diseases treatable by inhibition of BTK such as cancer, autoimmune, inflammatory, and thromboembolic diseases. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
1. A compound chosen from:
Name
Structure
(R)-2-(3-(8-amino-1- (2-fluoro-4- phenoxyphenyl) imidazo[1,5-a] pyrazin-3- yl)piperidine-1- carbonyl)-4-methyl- 4-(4-(oxetan- 3-yl)piperazin-1-yl) pent-2-enenitrile;
(S)-2-(2-((8-amino- 1-(2-fluoro-4- phenoxyphenyl) imidazo[1,5-a] pyrazin-3- yl)methyl) pyrrolidine- 1-carbonyl)-4,4- dimethylpent-2- enenitrile;
(S)-2-(2-((8-amino- 1-(2-fluoro-4- phenoxyphenyl) imidazo[1,5-a] pyrazin-3- yl)methyl) pyrrolidine-1- carbonyl)-4- methyl-4- morpholinopent- 2-enenitrile;
(S)-2-(2-((8- amino-1-(2- fluoro-4- phenoxyphenyl) imidazo[1,5-a] pyrazin-3- yl)methyl) pyrrolidine- 1-carbonyl)-4- methyl-4- (methyl(oxetan- 3-yl) amino)pent-2- enenitrile;
(S)-2-(2-((8-amino- 1-(2-fluoro-4- phenoxyphenyl) imidazo[1,5-a] pyrazin-3- yl)methyl) pyrrolidine-1- carbonyl)-4- methyl-4-(4- (oxetan-3-yl) piperazin-1-yl) pent-2-enenitrile; and
(R)-2-(3-(8-amino- 1-(4- phenoxyphenyl) imidazo[1,5-a] pyrazin-3- yl)piperidine- 1-carbonyl)-4- methyl-4-(4- (oxetan- 3-yl)piperazin- 1-yl)pent-2- enenitrile,
or a stereoisomer of any of the above compounds,
or an E or Z isomer thereof,
or a pharmaceutically acceptable salt of any of the above compounds.
2. The compound of claim 1 chosen from:
Name
Structure
(R)-2-(3-(8-amino-1-(2-fluoro-4- phenoxyphenyl)imidazo[1,5-a]pyrazin-3- yl)piperidine-1-carbonyl)-4-methyl-4-(4- (oxetan-3-yl)piperazin-1-yl)pent-2-enenitrile;
or a stereoisomer,
or an E or Z isomer thereof,
or a pharmaceutically acceptable salt thereof.
3. A pharmaceutical composition comprising:
a compound of claim 1 or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient.
4. A pharmaceutical composition comprising:
a compound of claim 2 or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient.