Pyrrolidinyl phenylurea derivatives as novel CCR3 antagonists

Bioorg Med Chem Lett. 2012 Nov 15;22(22):6876-81. doi: 10.1016/j.bmcl.2012.09.035. Epub 2012 Sep 20.

Abstract

Optimization starting with our lead compound 1 (IC(50)=4.9 nM) led to the identification of pyrrolidinyl phenylurea derivatives. Further modification toward improvement of the bioavailability provided (R)-1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2-hydroxyethoxy)phenyl)urea 32 (IC(50)=1.7 nM), a potent and orally active CCR3 antagonist.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Half-Life
  • Macaca fascicularis
  • Phenylurea Compounds / chemical synthesis
  • Phenylurea Compounds / chemistry*
  • Phenylurea Compounds / pharmacokinetics
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / chemistry*
  • Pyrrolidines / pharmacokinetics
  • Receptors, CCR3 / antagonists & inhibitors*
  • Receptors, CCR3 / metabolism

Substances

  • 1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2-hydroxyethoxy)phenyl)urea
  • Phenylurea Compounds
  • Pyrrolidines
  • Receptors, CCR3
  • pyrrolidine