Discovery of novel piperidine-substituted indolylarylsulfones as potent HIV NNRTIs via structure-guided scaffold morphing and fragment rearrangement

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• 作者：Xiao Li^a ; Ping Gao^a ; Boshi Huang^a ; Zhongxia Zhou^a ; Zhao Yu^a ; Zheng Yuan^c ; Huiqing Liu^c ; Christophe Pannecouque^b ; Dirk Daelemans^b ; Erik De Clercq^b ; Peng Zhan^a ; ^{zhanpeng1982@sdu.edu.cn} ; Xinyong Liu^a ; ^{xinyongl@sdu.edu.cn}
• 关键词：HIV ; NNRTIs ; Indolylarylsulfones ; Antiviral activity ; SAR ; Molecular modeling ; Chemical space ; Drug design
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：27 January 2017
• 年：2017
• 卷：126
• 期：Complete
• 页码：190-201
• 全文大小：1257 K
• 卷排序：126

文摘

Novel IASs bearing N-substituted piperidine at indole-2-carboxamide were designed. New IASs have EC50 values ranging from 0.62 μM to 0.006 μM against WT HIV-1. Compounds 8 (EC50 = 6 nM) and 18 (EC50 = 9 nM) were the most active derivatives. Compounds 8 and 18 also displayed outstanding potency against some HIV-1 mutants. SARs and molecular modeling studies were discussed in detail.