Synthesis and Evaluation of The Antiviral Activity of Novel 2-Thiopyrimidine-5-Carbonitrile Derivatives

Abstract

2-Thiouracil-5-carbonitriles are promising compounds that have been prepared in the last twenty years and have proven to have a diversity of biological activity. In line with this approach, our new compounds were prepared starting from Biginilli condensation of thiourea, ethyl cyanoacetate and 2,4-dichlorobenzaldehyde in basic medium to give a thiouracil derivative (1) which was subjected to chlorination at4 th position by POCl3/PCl5 mixture producing chloropyrimidine (2) which in turns was reacted with m-aminoacetophenone in pyridine yielding acetyl derivative (3) which was condensed with a series of four aromatic aldehydes in alcoholic sodium hydroxide producing chalcones (4a-d) which were used as starting materials for the preparation of many heterocyclic nuclei by their reaction with hydrazine, phenyl hydrazine, hydroxylamine HCl, thiourea, ethyl cyanoacetate /ammonium acetate, malononitrile, ethyl cyanoacetate/acetic acid/sodium acetate to give pyrazoline, phenyl pyrazoline, isoxazoline, thiopyrimidine, pyridinone, aminopyridine and aminopyran derivatives (5a-d) to (11a-d) respectively . Some of the newly synthesized compounds were investigated as antiviral agents. Compounds (2), (7a), and (7c) show promising antiviral activity against Bovine Viral Diarrhea Virus (BVDV). The structures of the newly synthesized compounds were confirmed by elemental analysis in addition to spectral data and physical methods.