Synthesis and Antitumor Evaluation of Novel Dihydropyrimidine, Thiazolo[3,2-a]Pyrimidine and Pyrano[2,3-d]Pyrimidine Derivatives

Abstract

A simple and efficient method has been developed for the synthesis of 4,5-dihydro-2-mercapto-4-oxo-6-substituted arylpyrimidine derivatives (2a-e) and their fused rings (3b, 4b, 5b & 6b) and also 1,4-dihydro-2-mercaptopyrimidine derivatives (7a-e) & (9a-e) using triethylamine as a catalyst. The structure of the newly synthesized compounds was confirmed on the basis of their spectral data and elemental analysis. All the synthesized compounds were evaluated for their in vitro anticancer activity against six human cancer cell lines and normal fibroblasts. Thirteen of the tested compounds: 2a-e, 3b, 4b, 5b, 7d, 8, 9a, 9c and 9d exhibited significant cytotoxicity against most cell lines. Among these derivatives compounds 2a, 3b and 9c are the most potent, they exhibited cytotoxic effect against the six cancer cell lines with IC₅₀ values < 330 nM compared to the standard CHS 828. Normal fibroblast cells (WI38) were affected to a much lesser extent (IC₅₀ >10,000 nM).