Vidyacharan Shinde, Adhikari Chandan, Krishna Vagolu Siva, Reshma Rudraraju Srilakshmi, Sriram Dharmarajan, Sharada Duddu S
Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Medak District 502285, Telangana, India.
Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, India.
Bioorg Med Chem Lett. 2017 Apr 1;27(7):1593-1597. doi: 10.1016/j.bmcl.2017.02.021. Epub 2017 Feb 20.
A facile and convenient approach has been developed for the synthesis of functionalized indazoles via solid state melt reaction using easily accessible starting materials under catalyst-free conditions. This transformation involves electrocyclization via a conjugated nitrene intermediate obtained under thermal conditions. Further anti-tubercular activity screening of the molecules was undertaken, among the compounds 3a-3x screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, compound 3u (MIC: 4.20μM) was found to be most active and are superior over existing standard drugs ciprofloxacin and ethambutol. Compounds 3c and 3x were found to equally potent as ethambutol. Among most potent compounds in the series, four compounds (3n, 3o, 3p and 3u) showed lower cytotoxicity which could be promising drug candidates for further development.
通过固态熔融反应，在无催化剂条件下使用易于获得的起始原料，开发了一种简便易行的方法来合成功能化吲唑。这种转化涉及通过热条件下获得的共轭氮烯中间体进行电环化。对这些分子进行了进一步的抗结核活性筛选，在针对结核分枝杆菌H37Rv进行体外抗分枝杆菌活性筛选的化合物3a - 3x中，发现化合物3u（MIC：4.20μM）活性最高，优于现有标准药物环丙沙星和乙胺丁醇。发现化合物3c和3x与乙胺丁醇效力相当。在该系列中最有效的化合物中，有四种化合物（3n、3o、3p和3u）显示出较低的细胞毒性，可能是有前景的进一步开发候选药物。
