Synthesis of 5-(1-H or 1-alkyl-5-oxopyrrolidin-3-yl)-8-hydroxy-[1,6]-naphthyridine-7-carboxamide inhibitors of HIV-1 integrase
Synthesis of 5-(1-H or 1-alkyl-5-oxopyrrolidin-3-yl)-8-hydroxy-[1,6]-naphthyridine-7-carboxamide inhibitors of HIV-1 integrase
复制标题
DOI：
10.1016/j.bmcl.2008.08.038
复制
发表时间：
2008-10-01
影响因子：
2.7
通讯作者：
Young, Steven D.
中科院分区：
文献类型：
--
作者：
Melamed, Jeffrey Y.;Egbertson, Melissa S.;Young, Steven D.
HIV-1整合酶催化病毒DNA插入宿主细胞的基因组中。整合酶抑制剂N-（4-氟苄基）-8-羟基-1，6-萘啶-7-甲酰胺选择性地抑制整合的链转移过程。4-在萘啶骨架的5-位引入在吡咯烷酮氮上具有各种基团的取代的吡咯烷酮。这些类似物在基于细胞的测定中表现出优异的抗病毒复制活性。这些化合物的制备能够通过三步，两锅反应序列从一个共同的丁烯二酰亚胺中间体。(c)2008爱思唯尔有限公司保留所有权利。
HIV-1 integrase catalyzes the insertion of viral DNA into the genome of the host cell. Integrase inhibitor N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide selectively inhibits the strand transfer process of integration. 4-Substituted pyrrolidinones possessing various groups on the pyrrolidinone nitrogen were introduced at the 5-position of the naphthyridine scaffold. These analogs exhibit excellent activity against viral replication in a cell-based assay. The preparation of these compounds was enabled by a three-step, two-pot reaction sequence from a common butenolide intermediate. (c) 2008 Elsevier Ltd. All rights reserved.