title: Synthesis of isotopically labeled daclatasvir for use in human clinical studies.
abstract: Daclatasvir is a novel hepatitis C virus NS5A inhibitor developed by Bristol-Myers Squibb and marketed as Daklinza®. The need to support the development of daclatasvir required the synthesis of carbon-14 labeled material for use in human absorption, distribution, metabolism, and excretion studies. A total of 7.53 mCi of [(14) C]-daclatasvir was synthesized in eight steps from commercially available [(14) C]-copper cyanide. The radiochemical purity was 99.6%, and specific activity was 3.86 μCi/mg. To support a human absolute bioavailability study, 5.56 g of [(13) C2 , (15) N4 ]-daclatasvir was synthesized in four steps.
authors.affiliation: Bristol-Myers Squibb Research and Development, Discovery Chemistry Platforms-Radiochemistry, 5 Research Parkway, Wallingford, CT, 06424, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Easter
authors.affiliation: Bristol-Myers Squibb Research and Development, Discovery Chemistry Platforms-Radiochemistry, 5 Research Parkway, Wallingford, CT, 06424, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Burrell
authors.affiliation: Discovery Chemistry Platforms-Radiochemistry, Route 206 and Province Line Road, Princeton, NJ, 08540, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Bonacorsi
mesh_terms: D001682:Biological Availability; D002219:Carbamates; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D007553:Isotope Labeling; D011759:Pyrrolidines; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D013722:Teprotide / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors
chemical_list: D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D017361:Viral Nonstructural Proteins; D013722:Teprotide; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; D014633:Valine; C549273:daclatasvir
keywords: HCV; carbon-14; daclatasvir; hepatitis C virus; stable isotope synthesis