The syntheses of isotopically labelled CB-1 antagonists for the treatment of obesity.
BMS-725519, BMS-811064, and BMS-812204 are potent and selective central cannabinoid receptor antagonists that have been investigated for the treatment of human obesity. To further understand their biotransformation profiles, radiolabelled and stable-labelled products were required. This paper describes the utility of [14C]1,1-carbonyldiimidazole as a radiolabelling reagent for the syntheses of carbonyl-labelled [14C]BMS-725519, [14C]BMS-811064, and [14C]BMS-812204. The syntheses of stable-labelled [13C6]BMS-725519 and [13CD313CD2]BMS-812204 synthesized from of [13C6]4-chloroacetophenone and [13CD313CD2]iodoethane, respectively, are also described.
Discovery Chemistry Platforms - Radiochemistry, Bristol-Myers Squibb, Inc, P.O. Box 4000, Princeton, NJ, 08543, USA.
Scott B
SB
Tran
Discovery Chemistry Platforms - Radiochemistry, Bristol-Myers Squibb, Inc, P.O. Box 4000, Princeton, NJ, 08543, USA.
Brad D
BD
Maxwell
Discovery Chemistry Platforms - Radiochemistry, Bristol-Myers Squibb, Inc, P.O. Box 5100, Wallingford, CT, 06492, USA.
Richard
R
Burrell
Discovery Chemistry Platforms - Radiochemistry, Bristol-Myers Squibb, Inc, P.O. Box 4000, Princeton, NJ, 08543, USA.
Samuel J
SJ
Bonacorsi
D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D002247:Carbon Isotopes / Q000737:chemistry; D002250:Carbon Radioisotopes / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D007093:Imidazoles / Q000737:chemistry; D007553:Isotope Labeling; D009765:Obesity / Q000188:drug therapy*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*
D019440:Anti-Obesity Agents; D002247:Carbon Isotopes; D002250:Carbon Radioisotopes; D007093:Imidazoles; D043884:Receptor, Cannabinoid, CB1; C029899:imidazole
CB-1 antagonists; carbon-13; deuterium; synthesis