Small molecule antagonists of the CCR2b receptor. Part 2: Discovery process and initial structure-activity relationships of diamine derivatives

Bioorg Med Chem Lett. 2004 Nov 1;14(21):5413-6. doi: 10.1016/j.bmcl.2004.08.009.

Abstract

Structure-activity relationships (SAR) of a weakly active class of CCR2b inhibitors were utilized to initiate a lead evolution program employing the Drug Discovery Engine. Several alternative structural series have been discovered that display nanomolar activity in the CCR2b binding and CCR2b-mediated chemotaxis assays.

MeSH terms

  • Cell Line
  • Chemokine CCL2 / metabolism
  • Chemotaxis / drug effects
  • Combinatorial Chemistry Techniques
  • Diamines / chemical synthesis*
  • Diamines / chemistry
  • Diamines / pharmacology
  • Drug Design
  • Humans
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology
  • Radioligand Assay
  • Receptors, CCR2
  • Receptors, Chemokine / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • CCR2 protein, human
  • Chemokine CCL2
  • Diamines
  • Piperidines
  • Pyrrolidines
  • Receptors, CCR2
  • Receptors, Chemokine