Design, synthesis, and antitubercular activity of 3-amidophenols with 5-heteroatomic substitutions
Niu-Niu Zhang1, Yun-Xiang Tang2,3, Lu Qian1
1Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Abstract:
A series of novel 3-amidophenols with 5-heteroatomic substitutions were designed and synthesized. Several compounds showed potent antitubercular activity against Mycobacterium tuberculosis H37Ra (MIC = 0.25-5 μg/mL). Compounds 12j and 14i also displayed good inhibitory activity against M. tuberculosis H37Rv and two clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.39-3.12 μg/mL). The privileged compound 14i showed certain oral efficacy on a mouse infection model. The compounds are non-cytotoxic against L-O2 hepatocytes and RAW264.7 macrophagocytes. They did not exert inhibitory activity against representative Gram-positive and Gram-negative bacteria.
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