Phenyl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors
The invention relates to inhibitors of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula: where A, B, W 1 , W 2 , W 3 , and R 1 -R 8 are described herein.
1. A compound of formula I:
or pharmaceutically acceptable salt thereof,
wherein:
W 1 and W 2 are CH;
W 3 is CR 2 ;
A is CN;
B is H or C 1 -C 6 alkoxy;
R 1 is halogen;
R 2 is H;
R 3 is H;
R 4 and R 5 are independently H or C 1 -C 3 alkyl;
R 6 , R 7 , and R 8 are independently H or C 1 -C 6 alkoxy.
2. The compound of claim 1 , wherein B is methoxy.
3. The compound of claim 2 , wherein R 4 is H and R 5 is methyl.
4. The compound of claim 3 , wherein R 4 is H and R 5 is (S)-methyl.
5. The compound of claim 4 , wherein R 1 is chloro.
6. The compound of claim 1 having the formula Ia:
or pharmaceutically acceptable salt thereof.
7. A pharmaceutical composition comprising (S)-4-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-2-methoxybenzonitrile, or a pharmaceutically acceptable salt thereof and pharmaceutically acceptable carrier.
8. A mixture comprising (S)-3-(1-aminoethyl)-6-chloroquinolin-2(1H)-one hydrochloride and 4-fluoro-2-methoxybenzonitrile.
9. The mixture of claim 8 , further comprising (S)-4-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-2-methoxybenzonitrile, or a pharmaceutically acceptable salt thereof and pharmaceutically acceptable carrier.