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

Bioorg Med Chem Lett. 2011 Dec 1;21(23):6950-4. doi: 10.1016/j.bmcl.2011.09.133. Epub 2011 Oct 8.

Abstract

A series of CCR5 antagonists were optimized for potent inhibition of R5 HIV-1 replication in peripheral blood mononuclear cells. Compounds that met acceptable ADME criteria, selectivity, human plasma protein binding, potency shift in the presence of α-glycoprotein were evaluated in rat and dog pharmacokinetics.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology
  • Animals
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • CCR5 Receptor Antagonists*
  • Dogs
  • Drug Design*
  • HIV-1*
  • Humans
  • Inhibitory Concentration 50
  • Leukocytes, Mononuclear* / drug effects
  • Molecular Structure
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Rats
  • Virus Replication / drug effects

Substances

  • Amides
  • Anti-HIV Agents
  • CCR5 Receptor Antagonists
  • Piperidines
  • Pyridines