CCR3 antagonists: a potential new therapy for the treatment of asthma. Discovery and structure-activity relationships

Bioorg Med Chem Lett. 2002 Jul 8;12(13):1785-9. doi: 10.1016/s0960-894x(02)00206-8.

Abstract

CCR3 antagonist leads with IC(50) values in the microM range were converted into low nM binding compounds that displayed in vitro inhibition of human eosinophil chemotaxis induced by human eotaxin. In particular, 4-benzylpiperidin-1-yl-n-propylureas and erythro-3-(4-benzyl-2-(alpha-hydroxyalkyl)piperidin-1-yl)-n-propylureas (obtained via Beak reaction of N-BOC-4-benzylpiperidine) exhibited single digit nanomolar IC(50) values for CCR3.

MeSH terms

  • Alkylation
  • Amides / chemistry
  • Amides / metabolism
  • Anti-Asthmatic Agents / chemistry*
  • Anti-Asthmatic Agents / pharmacology*
  • Calcium / metabolism
  • Chemokine CCL11
  • Chemokines, CC / metabolism
  • Chemotaxis, Leukocyte / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Piperidines / chemistry
  • Receptors, CCR3
  • Receptors, Chemokine / antagonists & inhibitors*
  • Receptors, Chemokine / chemistry
  • Receptors, Chemokine / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amides
  • Anti-Asthmatic Agents
  • CCL11 protein, human
  • CCR3 protein, human
  • Chemokine CCL11
  • Chemokines, CC
  • Ligands
  • Piperidines
  • Receptors, CCR3
  • Receptors, Chemokine
  • Calcium