Discovery of novel antitubercular 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues

• Published in: Bioorganic & medicinal chemistry letters 2011-09, Vol.21 (18), p.5259-5261
• Main Authors: Ahsan, Mohamed Jawed, Samy, Jeyabalan Govinda, Soni, Savita, Jain, Naresh, Kumar, Lalit, Sharma, Lalit K., Yadav, Hemant, Saini, Lokesh, Kalyansing, Rajput Gopal, Devenda, Narendra S., Prasad, Ravindra, Jain, Chandra Bhushan
• Format: Article
• Language: English
• Subjects: Animals; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular agents; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Biological and medical sciences; Cercopithecus aethiops; Drug Discovery; Indenes - chemical synthesis; Indenes - chemistry; Indenes - pharmacology; Medical sciences; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Pharmacology. Drug treatments; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrazolines; Stereoisomerism; Structure-Activity Relationship; Thioamides - chemical synthesis; Thioamides - chemistry; Thioamides - pharmacology; Vero Cells
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.07.035

Eighteen novel 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide analogues were designed and synthesized based on the structure of the known antitubercular agent, thiacetazone. The compound 4o (Ar1=4-fluorophenyl) was found to be active at 3.12μM and 6.25μM against MTB and INHR-MTB, respectively. In the present investigation, a series of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues were synthesized and were evaluated for antitubercular activity by two fold serial dilution technique. All the newly synthesized compounds showed low to high inhibitory activities against Mycobacterium tuberculosis H37Rv and INH resistant M. tuberculosis. The compound 3-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carbothioamide (4o) was found to be the most promising compound active against M. tuberculosis H37Rv and isoniazid resistant M. tuberculosis with minimum inhibitory concentration 3.12μM and 6.25μM, respectively.