Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4: synthesis and structure-activity relationships for 1-[N-(methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidin-1-yl)butanes

Bioorg Med Chem Lett. 2001 Sep 17;11(18):2475-9. doi: 10.1016/s0960-894x(01)00492-9.

Abstract

(2S)-2-(3-Chlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro(2,3-dihydrobenzthiophene-3,4'-piperidin-1'-yl)]butane S-oxide (1b) has been identified as a potent CCR5 antagonist having an IC50=10 nM. Herein, structure-activity relationship studies of non-spiro piperidines are described, which led to the discovery of 4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidine derivatives (3-5) as potent CCR5 antagonists.

MeSH terms

  • Animals
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology*
  • Butanes / chemical synthesis*
  • Butanes / chemistry*
  • Butanes / pharmacology*
  • CCR5 Receptor Antagonists*
  • Cells, Cultured
  • Cricetinae
  • Drug Design
  • Drug Evaluation, Preclinical
  • HIV-1 / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Neutrophils / drug effects
  • Neutrophils / virology
  • Piperidines / chemistry*
  • Piperidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Butanes
  • CCR5 Receptor Antagonists
  • Piperidines