Collect. Czech. Chem. Commun. 1996, 61, 791-798

New Groups of Potential Antituberculotics: 5-Alkylthio-1-aryltetrazoles

Karel Waissera, Jiří Kuneša, Alexandr Hrabáleka, Miloš Macháčeka and Želmíra Odlerováb

a Department of Inorganic and Organic Chemistry, Charles University, 500 05 Hradec Králové, Czech Republic
b Institute of Preventive and Clinical Medicine, 833 01 Bratislava, Slovak Republic


A series of 5-alkylthio-1-aryltetrazoles 1-14 was prepared by alkylation of the corresponding 1-aryltetrazole-5-thiols with alkyl bromides in the cyclohexane-aqueous potassium hydroxide system. The new compounds were evaluated for their activity against Mycobacterium tuberculosis, M. kansasii, M. avium and M. fortuitum. The effects of aryl and alkyl fragments on minimum inhibitory concentrations (MIC) against M. tuberculosis and M. kansasii were analyzed by Free-Wilson method. On basis of calculated fragment contributions, 5-butylthio-1-(3,4-dimethylphenyl)tetrazole (15) was predicted to be the most antimycobacterially active derivative in the present series studied and its activity was verified experimentally. MIC values of 30 μmol l-1 and 61 μmol l-1 were obtained for its activity against M. tuberculosis and M. kansasii, respectively.

Keywords: 5-Alkylthio-1-aryltetrazoles; Antituberculotics; Phase-transfer catalysis; Structure–activity relationships.