Preparation of pyridopyrimidine derivatives for use as cell proliferation inhibitors.

Abstract

Title compds. I [each X independently = N or CR5, wherein at most two may be N; Y = ; Z = ; R1 = H, (un)substituted alkyl, cycloalkyl, aryl, etc.; R2 = (un)substituted alkyl, aryl, heteroaryl, etc.; R3 = H, alkyl, halo, OH, etc.; R4 = H, CN, NO2, NH2, alkyl, etc.; R5 = H, CN, NO2, alkyl, alkoxy, etc.], and their pharmaceutically acceptable salts, are prepd. and disclosed as cell proliferation inhibitors. Thus, e.g., II was prepd. by amidation of 4-methoxy-3-trifluoromethylaniline with 4-methyl-3-nitrobenzoic acid followed by redn., heteroarylation with 4-amino-2,8-dichloropyrimido[5,4-d]pyrimidine (prepn. given), and amination with N-methylpiperazine. I were evaluated in B-RAF kinase assays, e.g., II demonstrated an IC50 value of 26 nM. [on SciFinder(R)]