Design, Synthesis and Evaluation of Novel Thiopyrimidine-Glucuronide Compounds with Promising Biological Activities

Abstract

3-Methyl-5-acetyl-7-[(2-sulfanylidene-6-aryl-1,2-dihydropyrimidin-4-yl)amino]-1,2-benzisoxazoles (2a-n) were obtained from N-(5-acetyl-3-methyl-1,2-benzoxazol-7-yl)-3-arylprop-2-enamides (1a-n) and thiourea. Products (2a-n) oxidized with KMnO4 to afford 5-acetyl-7-[(2-sulfanylidene-6-aryl-1,2- dihydropyrimidin-4-yl)amino]-1,2-benzisoxazole-3-carboxylic acids (3a-n). Reaction of 3a-n with D-gluconic acid and pyridine yielded β-D-glucuronosyl-5-acetyl-7-[(2-sulfanylidene-6-aryl-1,2- dihydropyrimidin-4-yl)amino]-1,2-benzisoxazol-3-carboxylates (4a-n). The present synthesis featured the formation of dihydropyrimidine skeleton through ring closure of key intermediates and installation of pyrimidine ring with amino group. The structures of all the newly synthesized compounds were characterized by analytical data, IR, 1 H NMR and mass spectrometry.