Synthesis of S-2-((S)-3-(4-chlorophenyl)-N'-((4-chlorophenyl)sulfonyl)-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboximidamido)-3-(methyl-d3 )butanamide-d5 , octadeuterated JD5037

J Labelled Comp Radiopharm. 2017 Aug;60(10):460-465. doi: 10.1002/jlcr.3521. Epub 2017 Aug 2.

Abstract

JD5037 (1) is a potent and selective, peripherally acting inverse agonist of the cannabinoid (CB1 R) receptor. Peripheral CB1 receptor antagonists/inverse agonists have great potential in the treatment of metabolic disorders like type 2 diabetes, obesity, and nonalcoholic steatohepatitis. We report the synthesis of octadeuterated [2 H8 ]-JD5037 (S, S) (8) along with its (S, R) diastereomer (13) from commercially available L-valine-d8 starting material. The [2 H8 ]-JD5037 compound will be used to quantitate unlabeled JD5037 during clinical ADME studies and will be used as an LC-MS/MS bioanalytical standard.

Keywords: ADME; CB1R; EC; PSA.

Publication types

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

MeSH terms

  • Amides / chemistry
  • Chemistry Techniques, Synthetic
  • Deuterium / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry*
  • Pyrazoles / metabolism
  • Receptor, Cannabinoid, CB1 / metabolism
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry*
  • Sulfonamides / metabolism

Substances

  • Amides
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Sulfonamides
  • Deuterium
  • JD5037