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Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities

Tijdschriftbijdrage - Tijdschriftartikel

A series of indazolyl-substituted piperidin-4-yl-aminopyrimidines (IPAPYs) were designed from two potent HIV-1 NNRTIs piperidin-4-yl-aminopyrimidine 3c and diaryl ether 4 as the lead compounds by molecular hybridization strategy. The target molecules 5a-q were synthesized and evaluated for their anti-HIV activities and cytotoxicities in MT-4 cells. 5a-q displayed moderate to excellent activities against wild-type (WT) HIV-1 with EC50 values ranging from 1.5 to 0.0064 μM. Among them, 5q was regarded as the most excellent compound against WT HIV-1 (EC50 = 6.4 nM, SI = 2500). And also, it displayed potent activities against K103 N (EC50 = 0.077 μM), Y181C (EC50 = 0.11 μM), E138K (EC50 = 0.057 μM), and moderate activity against double mutants RES056 (EC50 = 8.7 μM). Moreover, the structure-activity relationships (SARs) were summarized, and the molecular docking was performed to investigate the binding mode of IPAPYs and HIV-1 reverse transcriptase.
Tijdschrift: European Journal of Medicinal Chemistry
ISSN: 0223-5234
Volume: 186
Jaar van publicatie:2020
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:3
CSS-citation score:2
Auteurs:International
Authors from:Higher Education
Toegankelijkheid:Closed