Synthesis and Bioevaluation of 5-Chloro-4-(1,3-Oxazol-5-yl)-1Н-Pyrrole-3-Carboxyamides as Antimicrobial Agents

Abstract

This investigation deals with the design and synthesis of new derivatives of pyrrole consisting of modifying atoms of chlorine, amide, and 1,3-oxazole fragments. These compounds can be interesting in the context of research of new antimicrobial agents. Ethyl 5-chloro-4-formyl-1H-pyrrole-3-carboxylates were used as a key substrate for further transformation into target compounds. This process was realized as a direct transformation of an aldehyde fragment into a 1,3-oxazole cycle by van Leusen’s reaction followed by hydrolysis of an ester group, which finally converted a reactant into the corresponding pyrrole-3-carboxylic acid. This acid has been found to be an efficient construction block for the further development of antimicrobial agents. The preparative potential of these compounds has been verified by way of their transformation into a series of carbamides through consecutive reactions with thionyl chloride and alkyl-, aryl, and heterylamines under mild reaction conditions. According to bio screening results, the following two compounds have been chosen as those exhibiting a high anti-staphylococcus activity: 1-butyl-5-chloro-2-methyl-4-(1,3-oxazol-5-yl)-N-[(1,3-thiazol-2-yl]-1H-pyrrole-3-carboxamide and 1-butyl-5-chloro-N-[(3-dimethylaminosulfonyl)phenyl]-2-methyl-4-(1,3-oxazol-5-yl)-1H-pyrrole-3-carboxamide (МІС=7.8 µg/ml), while another one – 5-сhloro-N-(4-chlorophenyl)-4-(1,3-oxazol-5-yl)-2-phenyl-1-propyl-1H-pyrrole-3-carboxamide was selected as a compound exhibiting high antifungal activity (МІС=7.8 µg/ml) against the reference strains Candida albiсans АТСС 885/653 and Aspergillus niger K9.