Development of Water-Soluble 3,5-Dinitrophenyl Tetrazole and Oxadiazole Antitubercular Agents

Publication date: Available online 8 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Jaroslav Roh, Galina Karabanovich, Hana Vl ková, Alejandro Carazo, Jan N me ek, Pavel Sychra, Lenka Valášková, Oto Pavliš, Ji ina Stola íková, V ra Klimešová, Kate ina Vávrová, Petr Pávek, Alexandr Hrabálek
In this work, four series of tertiary amine-containing derivatives of 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents were prepared, and their in vitro antimycobacterial effects were evaluated. We found that the studied compounds showed lipophilicity-dependent antimycobacterial activity. The N-benzylpiperazine derivatives, which had the highest lipophilicity among all of the series, showed the highest in vitro antimycobacterial activities against Mycobacterium tuberculosis CNCTC My 331/88 (H37Rv), comparable to those of the first-line drugs isoniazid and rifampicin. The presence of two tertiary amines in these N-benzylpiperazine derivatives enabled us to prepare water-soluble dihydrochloride salts, overcoming the serious drawback of previously described 3,5-dinitrophenyl tetrazole and oxadiazole lead compounds. The water-soluble 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents described in this work are good candidates for further in vitro and in vivo pharmacokinetic and pharmacodynamic studies.

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