Inhibitors of HIV-1 attachment. Part 4: A study of the effect of piperazine substitution patterns on antiviral potency in the context of indole-based derivatives

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• 作者：Tao Wang ; John F. Kadow ; Zhongxing Zhang ; Zhiwei Yin ; Qi Gao ; Dedong Wu ; Dawn DiGiugno Parker ; Zheng Yang ; Lisa Zadjura ; Brett A. Robinson ; Yi-Fei Gong ; Wade S. Blair ; Pei-Yong Shi ; Gregory Yamanaka
• 关键词：HIV ; HIV attachment ; gp120 ; Piperazine ; A<sup>1 ; 3sup> strain
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：1 September 2009
• 年：2009
• 卷：19
• 期：17
• 页码：5140-5145
• 全文大小：435 K

文摘

4-Fluoro- and 4-methoxy-1-(4-benzoylpiperazin-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione (2 and 3, respectively) have been characterized as potent inhibitors of HIV-1 attachment that interfere with the interaction of viral gp120 with the host cell receptor CD4. As part of an effort to understand fundamental aspects of this pharmacophore, discovered originally using a high throughput cell-based screen, modification and substitution of the piperazine ring was examined in the context of compounds 6a–ah. The piperazine ring was shown to be a critical element of the HIV-1 attachment inhibiting pharmacophore, acting as a scaffold to deploy the indole glyoxamide and benzamide in a topographical relationship that complements the binding site on gp120.