Solid-Phase Synthesis of a Library of Pyrrolo[2,1-c][1,4]benzodiazepine-5,11-diones with Potential Antitubercular Activity

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• 作者：Ahmed Kamal ; K. Laxma Reddy ; V. Devaiah ; N. Shankaraiah ; G. Suresh Kumar Reddy ; Sadagopan Raghavan
• 刊名：Journal of Combinatorial Chemistry
• 出版年：2007
• 出版时间：January 2007
• 年：2007
• 卷：9
• 期：1
• 页码：29 - 42
• 全文大小：354K
• 年卷期：v.9,no.1(January 2007)
• ISSN：1520-4774

文摘

A versatile combinatorial approach was developed and utilized for the rapid synthesis of pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione (PBD-5,11-dione) libraries 10, 15, and 19 containing 210 compounds withvaried substitutions in A, B, and C rings. The key aspect of the synthetic strategy includes Staudinger,intermolecular aza-Wittig reaction followed by imine reduction and base-mediated cyclative cleavage resultsin the formation of final resin-free compounds. This strategy provides a highly efficient and practical protocolfor the parallel synthesis of PBD-5,11-diones on solid support. The modifications in the C-ring of the PBDscaffold produced three types of sublibraries. Reactions were monitored by FT-IR spectroscopy on the resinbeads. Further, from a generated library of 210 compounds, 142 compounds have been selected and evaluatedfor in vitro activity against Mycobacterium tuberculosis, and some of these compounds have exhibitedpromising activity.