Substituted nicotinamide 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 selected from the group consisting of: 5-(1-acryloylpiperidin-4-yl)-4′-phenoxybiphenyl-2-carboxamide; and 5-(4-acryloylpiperazin-1-yl)-4′-phenoxybiphenyl-2-carboxamide; or a pharmaceutically acceptable salt or solvate thereof
5-(1-acryloylpiperidin-4-yl)-4′-phenoxybiphenyl-2-carboxamide
5-(4-acryloylpiperazin-1-yl)-4′-phenoxybiphenyl-2-carboxamide.
2. A compound of 6-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)nicotinamide;
or a pharmaceutically acceptable salt or solvate thereof
6-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)nicotinamide.
3. A compound selected from the group consisting of:
6-(4-acryloylpiperazin-1-yl)-2-(4-phenoxyphenyl)nicotinamide;
6-(4-acryloylpiperazin-1-yl)-2-(4-(3-fluorophenoxy)phenyl)nicotinamide;
6-(4-acryloylpiperazin-1-yl)-2-(3-fluoro-4-phenoxyphenyl)nicotinamide;
6-(4-acryloylpiperazin-1-yl)-2-(4-(2-fluorophenoxy)phenyl)nicotinamide; and
6-(4-acryloylpiperazin-1-yl)-2-(2-fluoro-4-phenoxyphenyl)nicotinamide;
or a pharmaceutically acceptable salt or solvate thereof
6-(4-acryloylpiperazin-1-yl)-2-(4-phenoxyphenyl)nicotinamide;
6-(4-acryloylpiperazin-1-yl)-2-(4-(3-fluorophenoxy)phenyl)nicotinamide
6-(4-acryloylpiperazin-1-yl)-2-(3-fluoro-4-phenoxyphenyl)nicotinamide
6-(4-acryloylpiperazin-1-yl)-2-(4-(2-fluorophenoxy)phenyl)nicotinamide
6-(4-acryloylpiperazin-1-yl)-2-(2-fluoro-4-phenoxyphenyl)nicotinamide.
4. A compound selected from the group consisting of:
2-(4-phenoxyphenyl)-6-(4-(vinylsulfonyl)piperazin-1-yl)nicotinamide; and
2-(4-phenoxyphenyl)-6-(1-(vinylsulfonyl)piperidin-4-yl)nicotinamide;
or a pharmaceutically acceptable salt or solvate thereof
2-(4-phenoxyphenyl)-6-(4-(vinylsulfonyl)piperazin-1-yl)nicotinamide
2-(4-phenoxyphenyl)-6-(1-(vinylsulfonyl)piperidin-4-yl)nicotinamide.