Hit-to-lead optimization of pyrrolo[1,2-a]quinoxalines as novel cannabinoid type 1 receptor antagonists

Bioorg Med Chem Lett. 2009 Jul 1;19(13):3471-5. doi: 10.1016/j.bmcl.2009.05.010. Epub 2009 May 7.

Abstract

Hit-to-lead optimization of a novel series of N-alkyl-N-[2-oxo-2-(4-aryl-4H-pyrrolo[1,2-a]quinoxaline-5-yl)-ethyl]-carboxylic acid amides, derived from a high throughput screening (HTS) hit, are described. Subsequent optimization led to identification of in vitro potent cannabinoid 1 receptor (CB1R) antagonists representing a new class of compounds in this area.

MeSH terms

  • Animals
  • Binding Sites
  • Computer Simulation
  • Piperidines / chemistry
  • Pyrazoles / chemistry
  • Quinoxalines / chemical synthesis
  • Quinoxalines / chemistry*
  • Quinoxalines / pharmacology
  • Rats
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB1 / metabolism
  • Rimonabant
  • Structure-Activity Relationship

Substances

  • Piperidines
  • Pyrazoles
  • Quinoxalines
  • Receptor, Cannabinoid, CB1
  • Rimonabant