Synthesis of some dihydropyrimidine-based compounds bearing pyrazoline moiety and evaluation of their antiproliferative activity

摘要

Two series of 2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-1-methyl-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitriles >5a–>h and 4-(4-chlorophenyl)-2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5-carbonitriles >6a–h were synthesized via a cyclocondensation reaction of the corresponding 2-hydrazinopyrimidines >3a,b with the appropriate 2-propen-1-ones >4a–h. The target compounds were screened for their antiproliferative activity against A 549 (lung), HT 29 (colon), MCF 7 and MDA-MB 231 (breast) cell lines. The two most susceptible cell lines were the colon (HT 29) and breast (MDA-MB 231). Generally, the 4-unsubstitutedphenylpyrimidine derivatives >5a–h were more active than their 4-chlorophenylpyrimidine analogs >6a–h. Compounds >5e and >5g, showed high activity against three of the cell lines. The most active compound >5c possessed IC50 = 1.76 μM against A 549 cell line.