Synthesis of a cosalane analog with an extended polyanionic pharmacophore conferring enhanced potency as an anti-HIV agent

被引：15

作者：

Cushman, M ^{[1
]}

Insaf, S

Ruell, JA

Schaeffer, CA

Rice, WG

机构：

[1] Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharamacol, W Lafayette, IN 47907 USA

[2] NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Antiviral Drug Mechanisms, Frederick, MD 21702 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 07期

关键词：

D O I：

10.1016/S0960-894X(98)00121-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel cosalane analog having an extended polyanionic pharmacophore was synthesized in order to target specific cationic residues on the surface of CD4. The design rationale is based on a hypothetical binding model of cosalane to the surface of the protein. The new analog displayed an EC50 of 0.55 mu M as an inhibitor of the cytopathic effect of HIV-1(RF) in CEM-SS cells, which represents a significant increase in potency over cosalane itself (EC50 5.1 mu M) Both cosalane and the new analog are inhibitors of viral entry into target cells. (C) 1998 Elsevier Science Ltd. All rights reserved.

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页码：833 / 836

页数：4

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