Pyrazolo-Piperidines Exhibit Dual Inhibition of CCR5/CXCR4 HIV Entry and Reverse Transcriptase

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• 作者：Bryan D. Cox ; Anthony R. Prosser ; Yongnian Sun ; Zhufang Li ; Sangil Lee ; Ming B. Huang ; Vincent C. Bond ; James P. Snyder ; Mark Krystal ; Lawrence J. Wilson ; Dennis C. Liotta
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：July 9, 2015
• 年：2015
• 卷：6
• 期：7
• 页码：753-757
• 全文大小：356K
• ISSN：1948-5875

文摘

We report novel anti-HIV-1 agents with combined dual host鈥損athogen pharmacology. Lead compound 3, composed of a pyrazole-piperidine core, exhibits three concurrent mechanisms of action: (1) non-nucleoside reverse transcriptase inhibition, (2) CCR5-mediated M-tropic viral entry inhibition, and (3) CXCR4-based T-tropic viral entry inhibition that maintains native chemokine ligand binding. This discovery identifies important tool compounds for studying viral infectivity and prototype agents that block HIV-1 entry through dual chemokine receptor ligation.