Basic Quinolinonyl Diketo Acid Derivatives as Inhibitors of HIV Integrase and their Activity against RNase H Function of Reverse Transcriptase

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• 作者：Roberta Costi ; Mathieu M茅tifiot ; Suhman Chung ; Giuliana Cuzzucoli Crucitti ; Kasthuraiah Maddali ; Luca Pescatori ; Antonella Messore ; Valentina Noemi Madia ; Giovanni Pupo ; Luigi Scipione ; Silvano Tortorella ; Francesco Saverio Di Leva ; Sandro Cosconati ; Luciana Marinelli ; Ettore Novellino ; Stuart F. J. Le Grice ; Angela Corona ; Yves Pommier ; Christophe Marchand ; Roberto Di Santo
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：April 24, 2014
• 年：2014
• 卷：57
• 期：8
• 页码：3223-3234
• 全文大小：512K
• 年卷期：v.57,no.8(April 24, 2014)
• ISSN：1520-4804

文摘

A series of antiviral basic quinolinonyl diketo acid derivatives were developed as inhibitors of HIV-1 IN. Compounds 12d,f,i inhibited HIV-1 IN with IC₅₀ values below 100 nM for strand transfer and showed a 2 order of magnitude selectivity over 3鈥?processing. These strand transfer selective inhibitors also inhibited HIV-1 RNase H with low micromolar potencies. Molecular modeling studies based on both the HIV-1 IN and RNase H catalytic core domains provided new structural insights for the future development of these compounds as dual HIV-1 IN and RNase H inhibitors.