Certain pyrimidine derivatives as kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use and preparation thereof.

Abstract

The invention relates to pyrimidine derivs. as kynurenine-3-monooxygenase (KMO) inhibitors, their pharmaceutical compns. comprising at least one chem. entity and one or more pharmaceutically acceptable vehicle, their use in the treatment of KMO-mediated diseases. Compds. of formula I wherein R1 is (un)substituted aryl and (un)substituted heteroaryl; R2 is CN, (un)substituted heteroaryl and (un)substituted heterocyclyl; R3 is H and (un)substituted lower alkyl; R4 is H, halo, (un)substituted lower alkyl, OH, etc.; and pharmaceutically acceptable salts and prodrugs thereof, are claimed. Example compd. II was prepd. by cyanation of 4-chloro-6-(3-chlorophenyl)pyrimidine followed by heterocyclization and methylation. All the invention compds. were evaluated for their KMO inhibitory activity. From the assay, it was detd. that compd. II exhibited 65.67 % inhibition at 10 μM concn. [on SciFinder(R)]