2. Academic Validation
  3. 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

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

Affiliation

  • 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.

Figures