Spirocyclic compounds, potent CCR1 antagonists

Bioorg Med Chem Lett. 2013 Mar 15;23(6):1883-6. doi: 10.1016/j.bmcl.2012.12.095. Epub 2013 Jan 23.

Abstract

Conformationally constrained spirocycles (17-23) and (31-36) were synthesised. In vitro data revealed that these compounds are CCR1 antagonists with sub-nanomolar potency. In a functional assay 22, 23 and 36 inhibited CCR1 mediated chemotaxis with an IC50 value of 2, 2.6 and 68nM, respectively.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Cell Line
  • Chemotaxis / drug effects
  • Humans
  • Microsomes, Liver / metabolism
  • Piperidines / chemistry
  • Protein Binding
  • Rats
  • Receptors, CCR1 / antagonists & inhibitors*
  • Receptors, CCR1 / metabolism
  • Spiro Compounds / chemistry*
  • Spiro Compounds / metabolism
  • Spiro Compounds / pharmacology

Substances

  • Piperidines
  • Receptors, CCR1
  • Spiro Compounds
  • piperidine