A robust synthesis of functionalized 2H-indazoles via solid state melt reaction (SSMR) and their anti-tubercular activity.

Autor: Vidyacharan S; Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Medak District 502285, Telangana, India., Adhikari C; Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Medak District 502285, Telangana, India., Krishna VS; Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, India., Reshma RS; Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, India., Sriram D; Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, India., Sharada DS; Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Medak District 502285, Telangana, India. Electronic address: sharada@iith.ac.in.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2017 Apr 01; Vol. 27 (7), pp. 1593-1597. Date of Electronic Publication: 2017 Feb 20.
DOI: 10.1016/j.bmcl.2017.02.021
Abstrakt: 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.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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