顺式取代环己烯基和环己烷基核苷的合成及抗病毒评估

Synthesis and antiviral evaluation of cis-substituted cyclohexenyl and cyclohexanyl nucleosides.

作者信息

Barral Karine, Courcambeck Jérôme, Pèpe Gérard, Balzarini Jan, Neyts Johan, De Clercq Erik, Camplo Michel

机构信息

Laboratoire des Matériaux Moléculaires et des Biomatériaux, GCOM2, UMR CNRS 6114, Université de la Méditerranée, case 901, 163 av. de Luminy, 13288 Marseille Cedex 9, France.

出版信息

J Med Chem. 2005 Jan 27;48(2):450-6. doi: 10.1021/jm0493966.

DOI:10.1021/jm0493966

PMID:15658858

Abstract

Starting from commercially available (rac)-3-cyclohexene-1-carboxylic acid, a series of purine and pyrimidine cis-substituted cyclohexenyl and cyclohexanyl nucleosides were synthesized through a key Mitsunobu reaction. Antiviral evaluations were performed on HIV, coxsackie B3, and herpes viruses (HSV-1, HSV-2, VZV, HCMV). Three compounds showed moderate activity against HSV-1 and coxsackie viruses. Specific computer modeling studies were performed on HSV-1 thymidine kinase in order to understand the enzyme activation of an analogue showing moderate antiviral activity.

摘要

从市售的（外消旋）-3-环己烯-1-羧酸出发，通过关键的 Mitsunobu 反应合成了一系列嘌呤和嘧啶顺式取代的环己烯基和环己烷基核苷。对 HIV、柯萨奇 B3 病毒和疱疹病毒（HSV-1、HSV-2、VZV、HCMV）进行了抗病毒评估。三种化合物对 HSV-1 和柯萨奇病毒显示出中等活性。为了了解一种显示出中等抗病毒活性的类似物的酶激活作用，对 HSV-1 胸苷激酶进行了特定的计算机建模研究。