Synthesis of isotopically labeled daclatasvir for use in human clinical studies.

Daclatasvir is a novel hepatitis C virus NS5A inhibitor developed by Bristol-Myers Squibb and marketed as Daklinza r. 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 [14C]-daclatasvir was synthesized in eight steps from commercially available [14C]-copper cyanide. The radiochemical purity was 99.6%, and specific activity was 3.86 mu Ci/mg. To support a human absolute bioavailability study, 5.56 g of [13C2, 15N4]-daclatasvir was synthesized in four steps.