Discovery of a novel CCR5 antagonist lead compound through fragment assembly

Molecules. 2008 Oct 1;13(10):2426-41. doi: 10.3390/molecules13102426.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology
  • Butanones / chemical synthesis*
  • Butanones / pharmacology
  • CCR5 Receptor Antagonists*
  • Calcium Signaling / drug effects
  • Cyclohexanes
  • Drug Design
  • Humans
  • Maraviroc
  • Structure-Activity Relationship
  • Triazoles


  • Anti-HIV Agents
  • Butanones
  • CCR5 Receptor Antagonists
  • Cyclohexanes
  • Triazoles
  • Maraviroc