Discovery of a Novel CCR5 Antagonist Lead Compound Through Fragment Assembly

Discovery of a Novel CCR5 Antagonist Lead Compound Through Fragment Assembly

Hualiang Jiang, Jian Li, Xin Xie, Yu ZHANG, Jin Zhu, Kunqian Yu, Enkun Zhou, Yanqing Liu

CCR5, as the major co-receptor for HIV-1 entry, is an attractive novel target for the pharmaceutical industry in the HIV-1 therapeutic area. In this study, based on the structures of maraviroc and 1,4-bis(4-(7-chloroquinolin-4-yl)piperazin-1-yl)butane-1,4-dione (1), which was identified using structure-based virtual screening in conjunction with a calcium mobilization assay, a series of novel small molecule CCR5 antagonists have been designed and synthesized through fragment assembly. Preliminary SARs were obtained, which are in good agreement with the molecular binding model and should prove helpful for future antagonist design. The novel scaffold presented here might also be useful in the development of maraviroc-derived second generation CCR5 antagonists.

2008

CCR5 antagonist, fragment assembly, HIV-1, molecular modeling

DOI:

Molecules

MDPI AG

Organic chemistry

EN