Chloropyrimidines as a new class of antimicrobial agents

Abstract

In the course of our investigations of pyrimidines as antimycotic agents, we have idenified a sub-class, with significant in vitro activity agains mycobacteria. The salient feature of these pyrimidine derivatives (3a o and 7a,b) is their appended aryl, heteroaryl and alkylthio subst ituent a position 6 and also alkylthio substituent at position 2. The rational design, synthesis, and evaluation of the in vitro antibacterial activity against six pathogenic bacteria including virulent and non-virulent strains of M cobacterium tuberculosis is described. Some of the synthesized compounds (3c, 3h, 3i, 3o) have displayed only potent in vitro antimycobacterial activity with MIC of 0.75 μ/mL excep 3i which also demonstrated activity against Escherichia coli a 12.5 μg/mL concentration. Only two compounds, 3a and 3b, demonstrated antibacterial activity agains Pseudomonas aeruginosa and E. coli with MIC 12.5 μg/mL. All the synthesized compounds were also evaluated for their antimycotic activity agains five pathogenic fungi but only some of them 3j n and 7a,b were found most potent against Aspergillus fumigatus and Trichophyton mentagrophytes. Copyright © 2002 Elsevier Science Ltd. All righ s reserved.