Design and synthesis of pyridin-2-yloxymethylpiperidin-1-ylbutyl amide CCR5 antagonists that are potent inhibitors of M-tropic (R5) HIV-1 replication

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2450-5. doi: 10.1016/j.bmcl.2011.02.058. Epub 2011 Feb 23.

Abstract

A novel series of CCR5 antagonists were identified based on the redesign of Schering C. An SAR was established based on inhibition of CCR5 (RANTES) binding and these compounds exhibited potent inhibition of R5 HIV-1 replication in peripheral blood mononuclear cells.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacokinetics
  • Animals
  • CCR5 Receptor Antagonists*
  • Cyclic N-Oxides / chemistry*
  • Dogs
  • Drug Design
  • HIV-1 / drug effects*
  • Humans
  • Oximes
  • Piperidines / chemistry*
  • Pyridines / chemistry*
  • Rats
  • Receptors, CCR5 / metabolism
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • Amides
  • CCR5 Receptor Antagonists
  • Cyclic N-Oxides
  • Oximes
  • Piperidines
  • Pyridines
  • Receptors, CCR5
  • Ancriviroc