设计 2-吡咯烷酮类化合物作为 HIV-1 整合酶抑制剂。

Rational design of 2-pyrrolinones as inhibitors of HIV-1 integrase.

机构信息

Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.

出版信息

Bioorg Med Chem Lett. 2011 Nov 15;21(22):6724-7. doi: 10.1016/j.bmcl.2011.09.054. Epub 2011 Sep 20.

DOI:10.1016/j.bmcl.2011.09.054

PMID:21996518

Abstract

HIV-1 integrase is an essential enzyme for viral replication and a validated target for the development of drugs against AIDS. With an aim to discover new potent inhibitors of HIV-1 integrase, we developed a pharmacophore model based on reported inhibitors embodying structural diversity. Eight compounds of 2-pyrrolinones fitting all the features of the pharmacophore query were found through the screening of an in-house database. These candidates were successfully synthesized, and three of them showed strand transfer inhibitory activity, in which, one compound showed antiviral activity. Further mapping analysis and docking studies affirmed these results.

摘要

HIV-1 整合酶是病毒复制所必需的酶，也是开发抗艾滋病药物的有效靶点。为了发现新的强效 HIV-1 整合酶抑制剂，我们基于报道的具有结构多样性的抑制剂开发了一个药效团模型。通过对内部数据库的筛选，发现了 8 个符合药效团查询所有特征的 2-吡咯烷酮类化合物。这些候选化合物成功合成，其中 3 个具有链转移抑制活性，其中一个化合物具有抗病毒活性。进一步的映射分析和对接研究证实了这些结果。