Towards rational design of cannabinoid receptor 1 (CB1) antagonists for peripheral selectivity

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5711-4. doi: 10.1016/j.bmcl.2011.08.032. Epub 2011 Aug 11.

Abstract

CB1 receptor antagonists that are peripherally restricted were targeted. Compounds with permanent charge as well as compounds that have increased polar surface area were made and tested against CB1 for binding and activity. Sulfonamide and sulfamide with high polar surface area and good activity at CB1 were rationally designed and pharmacologically tested. Further optimization of these compounds and testing could lead to the development of a new class of therapeutics to treat disorders where the CB1 receptor system has been implicated.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • CHO Cells
  • Cannabinoid Receptor Modulators / chemical synthesis*
  • Cannabinoid Receptor Modulators / chemistry
  • Cannabinoid Receptor Modulators / metabolism
  • Cannabinoid Receptor Modulators / pharmacology*
  • Cell Line
  • Cricetinae
  • Dogs
  • Drug Design*
  • Drug Discovery*
  • Ligands
  • Molecular Structure
  • Piperidines / metabolism
  • Protein Binding
  • Pyrazoles / metabolism
  • Radioligand Assay
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB1 / chemistry
  • Rimonabant
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfonamides / chemistry

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cannabinoid Receptor Modulators
  • Ligands
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Sulfonamides
  • Rimonabant