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

Tao Wang, John F. Kadow, Zhongxing Zhang, Zhiwei Yin, Qi Gao, Dedong Wu, Dawn Di Giugno Parker, Zheng Yang, Lisa Zadjura, Brett A. Robinson, Yi Fei Gong, Wade S. Blair, Pei Yong Shi, Gregory Yamanaka, Pin Fang Lin, Nicholas A. Meanwell

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5140-5145
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number17
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

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Keywords

  • HIV
  • HIV attachment
  • Piperazine
  • gp120

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Wang, T., Kadow, J. F., Zhang, Z., Yin, Z., Gao, Q., Wu, D., Parker, D. D. G., Yang, Z., Zadjura, L., Robinson, B. A., Gong, Y. F., Blair, W. S., Shi, P. Y., Yamanaka, G., Lin, P. F., & Meanwell, N. A. (2009). 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. Bioorganic and Medicinal Chemistry Letters, 19(17), 5140-5145. https://doi.org/10.1016/j.bmcl.2009.07.076