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

doi:10.1016/j.bmcl.2009.07.076

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

55 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 language	English (US)
Pages (from-to)	5140-5145
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2009.07.076
State	Published - Sep 1 2009

Keywords

HIV
HIV attachment
Piperazine
gp120

ASJC Scopus subject areas

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

Access to Document

10.1016/j.bmcl.2009.07.076

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

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

Research output: Contribution to journal › Article › peer-review

Wang, T, Kadow, JF, Zhang, Z, Yin, Z, Gao, Q, Wu, D, Parker, DDG, Yang, Z, Zadjura, L, Robinson, BA, Gong, YF, Blair, WS, Shi, PY, 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

@article{7b7ec3e598604ce086c2320a19ad71b7,

title = "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",

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.",

keywords = "HIV, HIV attachment, Piperazine, gp120",

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

year = "2009",

month = sep,

day = "1",

doi = "10.1016/j.bmcl.2009.07.076",

language = "English (US)",

volume = "19",

pages = "5140--5145",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "17",

}

TY - JOUR

T1 - Inhibitors of HIV-1 attachment. Part 4

T2 - A study of the effect of piperazine substitution patterns on antiviral potency in the context of indole-based derivatives

AU - Wang, Tao

AU - Kadow, John F.

AU - Zhang, Zhongxing

AU - Yin, Zhiwei

AU - Gao, Qi

AU - Wu, Dedong

AU - Parker, Dawn Di Giugno

AU - Yang, Zheng

AU - Zadjura, Lisa

AU - Robinson, Brett A.

AU - Gong, Yi Fei

AU - Blair, Wade S.

AU - Shi, Pei Yong

AU - Yamanaka, Gregory

AU - Lin, Pin Fang

AU - Meanwell, Nicholas A.

PY - 2009/9/1

Y1 - 2009/9/1

N2 - 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.

AB - 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.

KW - HIV

KW - HIV attachment

KW - Piperazine

KW - gp120

UR - http://www.scopus.com/inward/record.url?scp=68349141359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68349141359&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2009.07.076

DO - 10.1016/j.bmcl.2009.07.076

M3 - Article

C2 - 19664921

AN - SCOPUS:68349141359

SN - 0960-894X

VL - 19

SP - 5140

EP - 5145

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 17

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this