Synthesis and structure-activity relationship study of 2-(substituted...

The synthesis and structure-activity relationship (SAR) study of a series of 2-(substituted benzylidene)-7-(4-fluorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)-one (4a-4j) derivatives as anticancer agents are described. This series of thiazolopyrimidines were synthesized by the reaction of 7-(4-fluoro phenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a] pyrimidin-3(7H)-one (3) with appropriate substituted aldehydes in the presence of anhydrous sodium acetate and glacial acetic acid. Their structures were confirmed by IR, (1)H-NMR, mass, and elemental analyses. These novel thiazolopyrimidine derivatives were screened for their anticancer activity on the U937 human histocytic lymphoma cell line by 3-(4,5-dimethyl thiazole-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. The comparison of anticancer activity of thiazolopyrimidine was performed considering their structures. This study was done using 2-(substituted benzylidene)-7-(4-fluorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)-one (4a-4j) as a basic model, showing that i) presence of a hydrogen donor/acceptor domain [thiazolo[3,2-a]pyrimidin-3(7H)-one] on the thiazolopyrimidine ring; ii) presence of a hydrophobic [(4-fluorophenyl)] aryl ring system on the thiazolopyrimidine ring; iii) presence of an electron donor moiety [5-(furan-2-yl)] on the thiazolopyrimidine ring; iv) ortho and para substitution of the distal aryl ring [2-(substituted benzylidene)] function strongly influenced anticancer activity. Among these compounds (4a-4j) para substituted derivatives 4c, 4e, 4f, 4g, 4h, and 4j showed significant anticancer activity.