CCR2B receptor antagonists: conversion of a weak HTS hit to a potent lead compound

Bioorg Med Chem Lett. 2000 Aug 21;10(16):1803-6. doi: 10.1016/s0960-894x(00)00347-4.

Abstract

A weak HTS hit at the CCR2B receptor has been converted into a potent antagonist by array SAR studies. Selectivity over the closely related CCR5 receptor is also achieved.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / metabolism
  • Amides / pharmacology*
  • Chemokine CCL2 / chemistry
  • Chemokine CCL2 / metabolism*
  • Chemotaxis, Leukocyte / drug effects
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / metabolism
  • Indoles / pharmacology*
  • Kinetics
  • Ligands
  • Molecular Structure
  • Monocytes / drug effects
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / metabolism
  • Piperidines / pharmacology*
  • Receptors, CCR2
  • Receptors, CCR5 / metabolism
  • Receptors, Chemokine / antagonists & inhibitors*
  • Receptors, Chemokine / chemistry
  • Receptors, Chemokine / metabolism
  • Structure-Activity Relationship

Substances

  • 3-(1-(((3-(3,4-dichlorophenyl)propenoyl)amino)pentyl)piperidin-4-yl)-5-hydroxyindole
  • Amides
  • CCR2 protein, human
  • Chemokine CCL2
  • Indoles
  • Ligands
  • Piperidines
  • Receptors, CCR2
  • Receptors, CCR5
  • Receptors, Chemokine