SCH 900567 is a specific inhibitor of tumor necrosis factor-alpha converting enzyme and is a potential candidate for the treatment of rheumatoid arthritis. [H-3]SCH 900567 was synthesized to support the initial drug metabolism and pharmacokinetics studies. Stable isotope-labeled [C-13(3), N-15]SCH 900567 was requested by the bioanalytical group as an internal standard for Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method development as well as by the drug metabolism and pharmacokinetics group for a potential microdose study. [C-13(3), N-15]SCH 900567 is synthesized via a linear sequence of seven steps from commercially available materials in 2.6% overall yield. [C-14]SCH 900567 was needed for a quantitative whole body autoradiography studies and was prepared from unlabeled Active Pharmaceutical Ingredient (API) via hydrolysis of the hydantoin moiety followed by rebuilding the hydantoin ring using potassium [C-14]cyanate to give the desired product in 42.8% overall yield. Activation of the hydantoin moiety of SCH 900567 to achieve hydrolysis followed by derivatization of the resulting amino acid to avoid decarboxylation during cyclization is also discussed.
Synthesis of [H-3], [C-13(3), N-15], and [C-14]SCH 900567
An inhibitor of TNF-alpha (tumor necrosis factor alpha) converting enzyme (TACE)
Ren, S., Hesk, D., McNamara, P., Koharski, D., & Borges, S. (2014). Synthesis of [H-3], [C-13(3), N-15], and [C-14]SCH 900567: An inhibitor of TNF-alpha (tumor necrosis factor alpha) converting enzyme (TACE). Journal of Labelled Compounds and Radiopharmaceuticals, 57(11), 632-636. https://doi.org/10.1002/jlcr.3229