Substituted purinone compounds

摘要

The invention relates to compounds of formula (I): (I) as described herein, pharmaceutical preparations comprising such compounds, uses and methods of use for such compounds in the treatment of a disorder or a disease mediated by the activity of as MDM2 and/or MDM4, and combinations comprising such compounds.;

主权项

1. A compound of formula (I), or a salt thereof,wherein
R1 is
(a) a phenyl substituted with one to five substituents each independently selected from halo, (C1-C4)alkyl and —O—(CH2)n—N(CH3)2, wherein n is 1 or 2; or(b) a 6-oxo-1,6-dihydropyridin-3-yl having Formula (Ia) or a 2-oxo-1,2-dihydropyridin-3-yl having Formula (Ib),  wherein R1a is H, halo or (C1-C4)alkyl, and R1b is H, (C1-C4)alkyl, —(CH2)m—N(CH3)2, or —(CH2)m—OR1c, where R1c is H or (C1-C4)alkyl, and m is 1 or 2; R2 is a phenyl substituted with one substituent in the para position selected from chloro, fluoro, trifluoromethyl, methyl and cyano and optionally one additional substituent selected from halo and (C1-C4)alkyl-, optionally substituted with (C1-C4)alkoxy; R3 is selected from isopropyl, cyclopropyl, isobutyl, cyclobutyl and cyclopentyl; R4 is halo, —(CH2)q-pyridyl, —(CH2)q-pyrimidyl, —(CH2)q-phenyl, where said pyridyl, said pyrimidyl, and said phenyl moieties are optionally substituted with one, two or three substituents each independently selected from halo, (C1-C4)alkoxy, cyano, —NH2, (C1-C4)alkyl-NH—, ((C1-C4)alkyl)2-N—, —(CH2)—OH, —C(O)—NH2, —C(O)—NH—(C1-C4)alkyl, —C(O)—N((C1-C4)alkyl)2, —C(O)—NH—(CH2)p—OH, —(CH2)—NH2, —(CH2)—NH—C(O)CH3 and —(CH2)—NH—C(O)H; p is 1 or 2, and q is 0 or 1.