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 DiGiugno 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

30 Citations (Scopus)

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

Fingerprint

Antiviral Agents
HIV-1
Substitution reactions
Derivatives
CD4 Antigens
Ethane
Scaffolds
Binding Sites
Throughput
piperazine
indole
benzamide
glyoxamide

Keywords

  • A strain
  • gp120
  • HIV
  • HIV attachment
  • Piperazine

ASJC Scopus subject areas

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

Cite this

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

In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 17, 01.09.2009, p. 5140-5145.

Research output: Contribution to journalArticle

Wang, T, Kadow, JF, Zhang, Z, Yin, Z, Gao, Q, Wu, D, Parker, DD, Yang, Z, Zadjura, L, Robinson, BA, Gong, YF, Blair, WS, Shi, P-Y, Yamanaka, G, Lin, PF & Meanwell, NA 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, vol. 19, no. 17, pp. 5140-5145. https://doi.org/10.1016/j.bmcl.2009.07.076
Wang, Tao ; Kadow, John F. ; Zhang, Zhongxing ; Yin, Zhiwei ; Gao, Qi ; Wu, Dedong ; Parker, Dawn DiGiugno ; Yang, Zheng ; Zadjura, Lisa ; Robinson, Brett A. ; Gong, Yi Fei ; Blair, Wade S. ; Shi, Pei-Yong ; Yamanaka, Gregory ; Lin, Pin Fang ; Meanwell, Nicholas A. / 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. In: Bioorganic and Medicinal Chemistry Letters. 2009 ; Vol. 19, No. 17. pp. 5140-5145.
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