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

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 cydocondensation 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 mu M against A 549 cell line. (C) 2013 Elsevier Masson SAS. All rights reserved.