A novel synthesis and preliminary in vitro cytotoxic evaluation of dihydropyrimidine-2,4(1H, 3 H)-dione derivatives

Abstract

We report the synthesis and characterization of four new compounds: 6-(2-(1H-inden-2-yl) phenyl)-3-(2-morpholinoethyl)dihydropyrimidine-2,4(1H,3H)-dione (13a), 6-(2-(1H-inden-2-yl)phenyl)-3-(2- (pyrrolidin-1-yl)ethyl)dihydropyrimidine-2,4(1H,3H)-dione (13b), 6-(2-(1H-inden-2-yl)phenyl)-3-phenethyldihydropyrimidine-2,4(1H,3H)-dione (13c) and 3-(3-(1H-imidazol-1-yl)propyl)-6-(2-(1H-inden-2-yl)phenyl) dihydropyrimidine-2,4(1H,3H)-dione (13d). A series of dihydropyrimidine-2,4(1H,3H)-dione moieties was derived from methyl 3-amino-3-(2-chlorophenyl)propanoate precursor in a multi-step synthesis. Acid-amine coupling of 3-(2-(1H-inden-2-yl)phenyl)-3-((tert-butoxycarbonyl)amino)propanoic acid with a series of amine derivatives under mild reaction conditions led to form the corresponding dihydropyrimidine-2,4(1H,3H)-dione derivatives via de-Boc and cyclization reaction in modest yield. Spectroscopic (1H, 13C NMR, and Mass) and analytical techniques have been used to identify and confirm the structure of the products. We have developed a new method for the synthesis of dihydropyrimidine-2,4-(1H,3H)-dione derivatives through a multi-step reaction with modest to high yields. NMR spectroscopy confirmed the structures of the synthesized compounds in each step. The biological evaluation of the synthesized compounds was tested against A431 cancer cell line.