Preparation of quinazolines and quinolines as inhibitors of prolylpeptidase, inducers of apoptosis and cancer treatment agents.

Abstract

The title compds. [I or II; Z = CH, N; Y = O, S; X = OR5, NR5R6; R1, R2 = H, NH2, CN, halo, OH, NO2 (wherein R1 and R2 are both not H); R3 = H, alkyl; R4 = (CH2)yR41 (R41 = (un)substituted alkyl; y = 0-2)], useful for the inhibiting the prolyl peptidase, inducing apoptosis and treating cancer, were prepd. Thus, reacting 2,4,6-trichloroquinazoline (prepn. given) with Me 4-(aminomethyl)benzoate.HCl in the presence of AcONa in H2O followed by treating the resulting Me 4-{[(2,6-dichloro-4-quinazolinyl)amino]methyl}benzoate with piperidine afforded I [Z = N; X = piperidino; R1 = H; R2 = Cl; R3 = H; R4 = 4-(MeO2C)C6H4CH2]. Most of the exemplified compds. I and II were found to inhibit prolylpeptidase at or below of 10 μM. [on SciFinder(R)]