新型取代的4,5-二氢-1H-1-吡唑基甲硫酮的抗结核活性

Antitubercular activity of novel substituted 4,5-dihydro-1H-1-pyrazolylmethanethiones.

作者信息

Ali Mohamed Ashraf, Yar Mohammad Shahar

机构信息

Faculty of Pharmacy, Jamia Hamdard University, Department of Pharmaceutical Chemistry, Hamdard Nagar, New Delhi 110062, India.

出版信息

J Enzyme Inhib Med Chem. 2007 Apr;22(2):183-9. doi: 10.1080/14756360601072437.

DOI:10.1080/14756360601072437

PMID:17518345

Abstract

A series of, anilino-5-(substituted) phenyl-3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolylmethanethione and 2-chloroanilino-5-(substituted) phenyl-3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolylmethanethione were synthesized by the reaction between hydrazine hydrate and the chalcones (3a-k) followed by condensation with the appropriate aryl isothiocyanate which yielded the N-substituted pyrazoline derivatives. These were tested for their in-vitro anti-mycobacterial activity against INH resistant Mycobacterium tuberculosis (INHR MTB) using the BACTEC 460 radiometric system. Compound 2-chloroanilino-5-(2,6-dichlorophenyl)-3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolyl-methanethione (6i) was found to be most active agent with a minimum inhibitory concentration of 0.96 microg/mL.

摘要

通过水合肼与查耳酮（3a - k）反应，随后与适当的芳基异硫氰酸酯缩合，合成了一系列的苯胺基 - 5 - （取代）苯基 - 3 - （4 - 羟基 - 3 - 甲基苯基） - 4,5 - 二氢 - 1H - 1 - 吡唑基甲硫酮和2 - 氯苯胺基 - 5 - （取代）苯基 - 3 - （4 - 羟基 - 3 - 甲基苯基） - 4,5 - 二氢 - 1H - 1 - 吡唑基甲硫酮，得到了N - 取代的吡唑啉衍生物。使用BACTEC 460放射性测量系统对这些衍生物针对耐异烟肼结核分枝杆菌（INHR MTB）的体外抗分枝杆菌活性进行了测试。发现化合物2 - 氯苯胺基 - 5 - （2,6 - 二氯苯基） - 3 - （4 - 羟基 - 3 - 甲基苯基） - 4,5 - 二氢 - 1H - 1 - 吡唑基甲硫酮（6i）是最具活性的药剂，最低抑菌浓度为0.96微克/毫升。