一种具有扩展聚阴离子药效基团的科萨烷类似物的合成，该类似物作为抗HIV药物具有增强的效力。

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

作者信息

Cushman M, Insaf S, Ruell J A, Schaeffer C A, Rice W G

机构信息

Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.

出版信息

Bioorg Med Chem Lett. 1998 Apr 7;8(7):833-6. doi: 10.1016/s0960-894x(98)00121-8.

DOI:10.1016/s0960-894x(98)00121-8

PMID:9871550

Abstract

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 microM as an inhibitor of the cytopathic effect of HIV-1RF in CEM-SS cells, which represents a significant increase in potency over cosalane itself (EC50 5.1 microM). Both cosalane and the new analog are inhibitors of viral entry into target cells.

摘要

为了靶向CD4表面特定的阳离子残基，合成了一种具有延伸多阴离子药效基团的新型科萨烷类似物。设计原理基于科萨烷与蛋白质表面的假设结合模型。作为HIV-1RF在CEM-SS细胞中细胞病变效应的抑制剂，新类似物的半数有效浓度（EC50）为0.55微摩尔，这表明其效力比科萨烷本身（EC50为5.1微摩尔）有显著提高。科萨烷和新类似物都是病毒进入靶细胞的抑制剂。