Discovery of novel 3-hydroxypicolinamides as selective inhibitors of HIV-1 integrase-LEDGF/p75 interaction

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• 作者：Feng-Hua Zhang^a ; Bikash Debnath^b ; Zhong-Liang Xu^a ; Liu-Meng Yang^c ; Li-Rui Song^a ; Yong-Tang Zheng^c ; Nouri Neamati^b ; ^{neamati@umich.edu} ; Ya-Qiu Long^a ; ^{yqlong@simm.ac.cn}
• 关键词：HIV-1 integrase ; Allosteric inhibitor ; LEDGF/p75 ; Dimerization ; 3-Hydroxypicolinamide
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：125
• 期：Complete
• 页码：1051-1063
• 全文大小：2258 K
• 卷排序：125

文摘

A new class of selective HIV-1 IN-LEDGF/p75 inhibitors without carboxylic acid/bioisostere are identified through scaffold hopping. The 3-hydroxypicolinamides function as dual HIV-1 IN inhibitors targeting IN-LEDGF/p75 interaction and IN dimerization with anti-HIV effect. The binding mode of the novel IN-LEDGF/p75 inhibitors was established through shape-based ROCS pharmacophore model.