Indole-based allosteric inhibitors of HIV-1 integrase

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• 作者：Pratiq A. Patel^a ; ^b ; ^&dagger ; ; Nina Kvaratskhelia^c ; ^&dagger ; ; Yara Mansour^a ; ^d ; Janet Antwi^a ; Lei Feng^c ; Pratibha Koneru^c ; Mathew J. Kobe^c ; Nivedita Jena^a ; Guqin Shi^a ; Mosaad S. Mohamed^d ; Chenglong Li^a ; Jacques J. Kessl^c ; ^{jacques.kessl@usm.edu" class="auth_mail" title="E-mail the corresponding author} ; James R. Fuchs^a ; ^{fuchs.42@osu.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：HIV integrase inhibitor ; ALLINI ; Scaffold hopping
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 October 2016
• 年：2016
• 卷：26
• 期：19
• 页码：4748-4752
• 全文大小：1215 K

文摘

Employing a scaffold hopping approach, a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) have been synthesized based on an indole scaffold. These compounds incorporate the key elements utilized in quinoline-based ALLINIs for binding to the IN dimer interface at the principal LEDGF/p75 binding pocket. The most potent of these compounds displayed good activity in the LEDGF/p75 dependent integration assay (IC₅₀ = 4.5 μM) and, as predicted based on the geometry of the five- versus six-membered ring, retained activity against the A128T IN mutant that confers resistance to many quinoline-based ALLINIs.