Design, synthesis and antimycobacterial activity of some novel 3,5-dichloro-2-ethoxy-6-fluoropyridin-4 amine cyclocondensed dihydropyrimidines

Abstract

Background/aimPyrimidine is found as a core structure in a large variety of compounds that exhibit important biological activity. Specifically, 2,4,5,6-tetrasubstituted dihydropyrimidines have shown potent antimycobacterial activity. The use of combinatorial approaches toward the synthesis of drug-like scaffolds is a powerful tool in helping to speed up drug discovery. Recently, we have developed a laboratory made para toluenesulfonic acid (PTSA) as an efficient catalyst to generate 2,4,5,6-substituted dihydropyrimidine libraries using a one-pot multicomponent reaction. MethodsBased on the activity of compound 7a, a series of novel 2,4,5,6-pyrimidine derivatives were synthesized by reacting N-(3,5-dichloro-2-ethoxy-6-fluoropyridin-4-yl)-3-oxobutanamide, urea or thiourea and appropriate aldehyde in the presence of catalytic amount of PTSA as an efficient catalyst using modifications at the 4th-position of the dihydropyrimidine moiety. Synthesized compounds analyzed by melting point, thin layer chromatography (TLC), IR, 1H NMR, mass spectra and in vitro antimycobacterial activity. ResultsAmong the synthesized compounds, compound N-(3,5-dichloro-2-ethoxy-6-fluoropyridin-4-yl)-4-(4-fluorophenyl)-6-methyl-2-oxo-1, 2, 3, 4-tetrahydropyrimidine-5-carboxamide (7j) was found to be the most potent against Mycobacterium tuberculosis CIP 103471 and M. tuberculosis H37Rv ATCC with minimum inhibitory concentration (MIC) 1.13 and 1.09 μg/ml respectively. ConclusionA series of novel Biginelli dihydropyrimidines of biological interest were synthesized and analyzed for their structures. Our present study makes it an interesting compound when compared to the current therapeutic agents and are considered the candidates to investigate further for the same.