Synthesis of 3-phenylsulfonylmethyl cyclohexylaminobenzamide-derived antagonists of CC chemokine receptor 2 (CCR2)

Bioorg Med Chem Lett. 2012 Feb 1;22(3):1384-7. doi: 10.1016/j.bmcl.2011.12.057. Epub 2011 Dec 16.

Abstract

We report the synthesis of 3-phenylsulfonylmethyl cyclohexylaminobenzamides (4) as CCR2 inhibitors for the potential treatment of inflammatory diseases. Several of the compounds display nanomolar binding affinity for CCR2. The in vitro structure-activity relationships of 4 are described, and are also reconciled with those from the related 2-phenylsulfonylmethyl series.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology
  • Aminobenzoates / chemical synthesis*
  • Aminobenzoates / chemistry
  • Aminobenzoates / pharmacology
  • Animals
  • Cyclization
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Microsomes / enzymology
  • Models, Molecular*
  • Molecular Structure
  • Protein Binding / drug effects
  • Rats
  • Receptors, CCR2 / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Substrate Specificity
  • Sulfur / chemistry*
  • Sulfur / pharmacology

Substances

  • Amides
  • Aminobenzoates
  • Receptors, CCR2
  • Sulfur