Fused-bicyclic aryl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors
AssigneeForma Tm2, Inc.
InventorsJian Lin, Anna Ericsson, Ann-Marie Campbell, Gary Gustafson, Zhongguo Wang, R. Bruce Diebold, Susan Ashwell, David R. Lancia, Jr., Justin Andrew Caravella, Wei Lu
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Abstract
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 (I) where A, B, U, V, Z, W1, W2, W3, and R1-R6 are described herein.
Claims16
A compound of formula I:
- or a pharmaceutically acceptable salt thereof,
- wherein:
- each W1 and W2 is independently CH;
- W3 is CR2;
- U is N;
- V is N;
- Z is C;
- indicates a single or double bond but never two double bonds adjacent to one another in the ring in which the occurs;
- A and B, are taken together with the atoms to which they are attached and form a 5 to 7-membered heterocyclyl or heteroaryl ring system which can be further substituted with one or more R10 substituents;
- R1 is halogen;
- R2 is H;
- R3 is H;
- R4 and R5 are independently H or C1-C3 alkyl;
- R6 is H;
- and
- each R10 is independently C1-C6 alkyl, ═O, or —C(O)R11;
- R11 is C1-C6 alkyl.
A pharmaceutical composition comprising 6-chloro-3-[(1S)-1-({1-methyl-2-oxo-1H,2H,4H-pyrimido[4,5-d][1,3]oxazin-7-yl}amino)ethyl]-1,2-dihydroquinolin-2-one or a pharmaceutically acceptable salt thereof and pharmaceutically acceptable carrier.
A mixture comprising (S)-3-(1-aminoethyl)-6-chloroquinolin-2(1H)-one hydrochloride and 7-chloro-1-methyl-1H-pyrimido[4,5-d][1,3]oxazin-2(4H)-one.
Dependencies are inferred from the claim text.