Synthesis of a dual carbon‐14‐labeled calcitonin gene‐related peptide receptor antagonist for use in a human absorption–distribution–metabolism–elimination study. (10th March 2022)

• Record Type: Journal Article
• Authors: Turley, Wesley A.; Easter, John A.; Burrell, Richard C.; Bonacorsi, Samuel J.
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 65:Number 5(2022)
• Page Start: 126
• Page End: 139
• Publication Date: 2022-03-10
• Subjects: carbon‐14 synthesis -- CGRP receptor antagonists -- human ADME study; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3966
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : Oral calcitonin gene‐related peptide (CGRP) receptor antagonists have been shown to be effective in the acute and preventive treatment of migraine. CGRP receptor antagonists offer safety advantages over triptans because they are not active vasoconstrictors, which reduces cardiovascular risks. Bristol Myers Squibb discovered a high affinity CGRP receptor antagonist BMS‐927711 for the treatment of migraine now FDA approved as Nurtec® ODT (rimegepant). Dual‐labeled [ 14 C]‐BMS‐927711 was prepared and used in a human absorption–distribution–metabolism–elimination (ADME) study. A dual‐labeled analog of BMS‐927711 was required to fully track the compound's metabolic transformation. The carbon‐14‐labeled synthesis of both right side and left side portions of [ 14 C]‐BMS‐927711 is described. Abstract : Oral calcitonin gene‐related peptide (CGRP) receptor antagonists have been shown to be effective in the acute and preventive treatment of migraine. Bristol Myers Squibb discovered high‐affinity CGRP receptor antagonist BMS‐927711 (Nurtec® ODT [rimegepant]). Dual‐labeled [14C]‐BMS‐927711 was prepared and used in a human absorption–distribution–metabolism–elimination (ADME) study. A dual‐labeled analog of BMS‐927711 was required to fully track the compound's metabolic transformation. The carbon‐14‐labeled synthesis of both right side and left side portions of [14C]‐BMS‐927711 is described.