Studies on the structure-activity relationship of 1,3,3,4-tetra-substituted pyrrolidine embodied CCR5 receptor antagonists. Part 2: Discovery of highly potent anti-HIV agents

  • Bioorg Med Chem Lett. 2010 Sep 1;20(17):5334-6. doi: 10.1016/j.bmcl.2010.05.046.
Ben Li  1 ,  Eric Dale Jones ,  Enkun Zhou ,  Li Chen ,  Dean Cameron Baylis ,  Shanghai Yu ,  Miao Wang ,  Xing He ,  Jonathan Alan Victor Coates ,  David Ian Rhodes ,  Gang Pei ,  John Joseph Deadman ,  Xin Xie ,  Dawei Ma
Affiliations
  • 1. Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
PMID: 20674358 DOI: 10.1016/j.bmcl.2010.05.046
Abstract

Modification of 1,3,3,4-tetra-substituted pyrrolidine embodied CCR5 receptor antagonists revealed that introducing a fluoro group at the 3-position of the 3-phenyl group to reduce metabolism did not adversely affect the high potency against HIV Infection, and that replacing the piperidine ring with a tropane ring could deliver the most potent anti-HIV agents. Stereochemistry of the substituted tropane ring is essential for maintaining the potent anti-HIV activity because only exo-isomers displayed subnanomolar whole cell activity.