Discovery of 1-[9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylaminopiperidine-4-carboxylic acid amide hydrochloride (CP-945,598), a novel, potent, and selective cannabinoid type 1 receptor antagonist

J Med Chem. 2009 Jan 22;52(2):234-7. doi: 10.1021/jm8012932.

Abstract

We report the structure-activity relationships, design, and synthesis of the novel cannabinoid type 1 (CB1) receptor antagonist 3a (CP-945,598). Compound 3a showed subnanomolar potency at human CB1 receptors in binding (Ki = 0.7 nM) and functional assays (Ki = 0.12 nM). In vivo, compound 3a reversed cannabinoid agonist-mediated responses, reduced food intake, and increased energy expenditure and fat oxidation in rodents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dogs
  • Drug Discovery
  • Energy Metabolism
  • Fats / metabolism
  • Oxidation-Reduction
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Purines / chemistry
  • Purines / pharmacology*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • 1-(9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl)-4-ethylaminopiperidine-4-carboxylic acid amide
  • Fats
  • Piperidines
  • Purines
  • Receptor, Cannabinoid, CB1