Synthesis and SAR Study of Novel Amidino 2-substituted Benzimidazoles as Potential Antibacterial Agents

[摘要] A series of novel 2-substituted benzimidazole derivatives were synthesized and their antibacterial activity was assessed against selected Gram-positive and Gram-negative bacteria. The specific moiety at the 2-position of the benzimidazole was extensively modified with several fused heterocyclic functional groups containing nitrogen and sulfur heteroatoms. In addition, the influence of different amidino groups at the position 5 of benzimidazole scaffold was evaluated. The values of clogP (a partition coefficient) and clogD7.5 (calculated distribution coefficient, pH 7.5) were determined and the lipophilic character of compounds has been found to be important parameter for the observed activity of the tested benzimidazole derivatives against Moraxella catarrhalis. The indolo 2-substituted benzimidazole 13a demonstrated solid activity against Staphylococcus aureus (MICs 16 µg/mL) and Moraxella catarralis (MICs 2 µg/mL) and represents promising lead molecule for further optimization.

[学科分类] 化学（综合）

[关键词] amidines;benzimidazoles;antibacterial activity;Moraxella catarrhalis;lipophilicity