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.

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.