期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 26, 期 21, 页码 5664-5671出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2018.10.011
关键词
CD4 mimic; Oxalamide linker; Indole; Entry inhibitor; Anti-HIV
资金
- Japan Agency for Medical Research and Development, (AMED) [18fk0410002h0003, 18fk0410006h0303]
- Ministry of Education, Culture, Sports, Science, and Technology of Japan (JSPS KAKENHI) [JP15H04652]
- Platform for Drug Discovery, Informatics, and Structural Life Science of MEXT, Japan
- Cooperative Research Project of Research Center for Biomedical Engineering
CD4 mimics such as YIR-821 and its derivatives are small molecules which inhibit the interaction between the Phe43 cavity of HIV-1 gp120 with host CD4, an interaction that is involved in the entry of HIV to cells. Known CD4 mimics generally possess three structural features, an aromatic ring, an oxalamide linker and a piperidine moiety. We have shown previously that introduction of a cyclohexyl group and a guanidine group into the piperidine moiety and a fluorine atom at the meta-position of the aromatic ring leads to a significant increase in the anti-HIV activity. In the current study, the effects of conformational flexibility were investigated by introduction of an indole-type group in the junction between the oxalamide linker and the aromatic moiety or by replacement of the oxalamide linker with a glycine linker. This led to the development of compounds with high anti-HIV activity, showing the importance of the junction region for the expression of high anti-HIV activity. The present data are expected to be useful in the future design of novel CD4 mimic molecules.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据