Pyridin-2(1H)-one quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors
The application relates to an inhibitor of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula (I-13):
1. A composition comprising a compound of Formula (I-13) in an enantiomeric purity (e.e. %) of at least 98% as determined by chiral HPLC analysis:
2. The composition of claim 1 , further comprising a compound of Formula (III-1):
3. The composition of claim 1 , further comprising a compound of Formula (II-1):
4. The composition of claim 3 , further comprising a compound of Formula (III-1):
5. The composition of claim 1 , wherein the compound of Formula (I-13) is obtained by a process comprising the step of reacting a compound of Formula (II-1) with a compound of Formula (III-1) to obtain the compound of Formula (I-13):
6. The composition of claim 1 , further comprising a compound of Formula (V-2):
7. The composition of claim 1 , further comprising a compound of Formula (IV-1)
8. The composition of claim 1 , wherein the compound of Formula (I-13) is obtained by a process comprising the step of reacting a compound of Formula (IV-1) with a compound of Formula (V-2):
9. A pharmaceutical composition for inhibiting mutant IDH1, comprising a mutant IDH1 inhibitor consisting of a compound of Formula (I-13) in an enantiomeric purity (e.e. %) of at least 98% as determined by chiral HPLC analysis, and a pharmaceutically acceptable carrier:
10. The pharmaceutical composition of claim 9 , formulated in a dosage form for oral administration.
11. The pharmaceutical composition of claim 10 , formulated in a solid dosage form for oral administration.
12. The pharmaceutical composition of claim 9 , formulated as a tablet or capsule dosage form.
13. The pharmaceutical composition of claim 11 , comprising a total of about 50 mg of a compound of Formula (I-13).
14. The pharmaceutical composition of claim 11 , comprising a total of about 150 mg of a compound of Formula (I-13).
15. The pharmaceutical composition of claim 9 , further comprising a compound of Formula (II-1):
16. The pharmaceutical composition of claim 15 , further comprising a compound of Formula (III-1):
17. The pharmaceutical composition of claim 9 , further comprising a compound of Formula (III-1):
18. The pharmaceutical composition of claim 9 , wherein the compound of Formula (I-13) is obtained by a process comprising the step of reacting a compound of Formula (II-1) with a compound of Formula (III-1) to obtain the compound of Formula (I-13):
19. A pharmaceutical composition for inhibiting mutant IDH1, comprising a pharmaceutically acceptable carrier and from about 5% to about 90% by weight of a mutant IDH1 inhibitor consisting of the compound 5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl] amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile.
20. The pharmaceutical composition of claim 19 , formulated as a solid dosage form for oral administration, and comprising about 50-150 mg of the compound 5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl] amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile in an enantiomeric purity (e.e. %) of at least 98% as determined by chiral HPLC analysis.