Racemic and chiral lactams as potent, selective and functionally active CCR4 antagonists

Bioorg Med Chem Lett. 2004 Nov 15;14(22):5537-42. doi: 10.1016/j.bmcl.2004.09.001.

Abstract

A series of racemic and chiral, nonracemic lactams that display high binding affinities, functional chemotaxis antagonism, and selectivity toward CCR4 are described. Compound 41, which provides reasonably high blood levels in mice when dosed intraperitoneally, was identified as a useful pharmacological tool to explore the role of CCR4 antagonism in animal models of allergic disease.

MeSH terms

  • Animals
  • Binding Sites
  • Binding, Competitive / drug effects
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Hypersensitivity / drug therapy
  • Lactams / chemical synthesis
  • Lactams / chemistry*
  • Lactams / pharmacokinetics*
  • Mice
  • Molecular Structure
  • Receptors, CCR4
  • Receptors, Chemokine / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Ccr4 protein, mouse
  • Lactams
  • Receptors, CCR4
  • Receptors, Chemokine