Synthesis of New Pyrimidinone Derivatives and Their Respective Biological Activity Assessment

Abstract

Barbituric acid is converted into a pyrimidinone-incorporated pyrazolyl moiety (1), which is a key starting material. 1 can be converted into pyrimidine dione, isoxazole, pyrimidopyrimidine, and pyranopyrimidine by reacting with hydrazine hydrate and/or phenyl hydrazine, hydroxyl amine, urea, thiourea, guanidine, ethyl acetoacetate and ethyl cyanoacetate. Acylation of 1 gave an important key intermediate (7), which was condensed to form chalcone, which then underwent cycloaddition into cyclohexenes (8-13). Some newly synthesized compounds were screened as anti-diabetic agents and exhibited significant activity. These freshly manufactured compounds were characterized using different methods. These compounds showed significant activity as anti-diabetic agents, especially compound 4b, with IC50= 13.54 μg/ml, which is very close to that of the standard acarbose (IC50= 12.87 µg/ml). Additionally, these compounds showed cytotoxic inhibition activity against the colon carcinoma (HCT116), hepatocellular carcinoma (HEPG2), and breast carcinoma (MCF7) cells; compounds 11, 4b, and 10 showed the best activity, with IC50 = 19.3, 2.6, and 5 μg/ml, respectively.