Abstract: 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.