title: Synthesis of C-14 radiolabeled glucagon receptor antagonist and its use in a human mass balance study.
abstract: The synthesis of the radiolabeled glucagon receptor antagonist 1-[14C] was accomplished based on decarboxylative iodination of acid 2 followed by "reattachment" of14C carboxylic function. The method allowed a significant reduction in the number of steps in preparation of the radiolabeled compound. Iodide 4, obtained by the halodecarboxylation, was converted to cyanide 5-[14C], which was hydrolyzed to provide the radiolabeled acid 2-[14C]. Coupling with β-alanine fragment and hydrolysis of ester 6-[14C] completed the synthesis of the target molecule 1-[14C]. The resulting compound was utilized in a mass balance and metabolism study where hepatic oxidation followed by a trace amount of sulfate conjugation and elimination was the main clearance pathway for 1 in humans.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Czeskis
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Darlene K
authors.initials: DK
authors.lastname: Satonin
mesh_terms: D000328:Adult; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry; D002250:Carbon Radioisotopes / Q000737:chemistry; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008875:Middle Aged; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: C000625390:3-(4-(1-(4'-tert-butyl-2,6-dimethylbiphenyl-4-yloxy)-4,4,4-trifluorobutyl)benzamido)propanoic acid; D001549:Benzamides; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D018027:Receptors, Glucagon; D015091:beta-Alanine
keywords: carbon-14; decarboxylative halogenation; glucagon receptor antagonist; metabolism; radiolabeled; synthesis