Synthesis of Radiolabeled and Stable-Isotope Labeled Deucravacitinib (BMS-986165)

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Biochemistry

Background:

• Deucravacitinib is an approved allosteric inhibitor of tyrosine kinase 2 (TYK2).
• Tyrosine kinase 2 (TYK2), a Janus (JAK) family kinase, regulates inflammatory cytokine production.
• Plaque psoriasis is a moderate to severe inflammatory condition treated with TYK2 inhibitors.

Purpose of the Study:

• To describe the synthesis of ¹⁴C-radiolabeled deucravacitinib.
• To outline the preparation of stable-isotope labeled deucravacitinib variants.
• To provide synthetic routes for labeled deucravacitinib for research purposes.

Main Methods:

• Chemical synthesis of ¹⁴C-radiolabeled deucravacitinib.
• Synthesis of stable-isotope labeled deucravacitinib using deuterium and/or carbon-13.
• Purification and characterization of labeled compounds.

Main Results:

• Successful synthesis of ¹⁴C-deucravacitinib with high radiochemical purity.
• Efficient preparation of stable-isotope labeled deucravacitinib.
• Characterization data confirming the structure and isotopic enrichment of the labeled molecules.

Conclusions:

• The described synthetic methods enable the production of essential labeled deucravacitinib compounds.
• These labeled variants are crucial for pharmacokinetic, metabolism, and distribution studies of deucravacitinib.
• This work supports further research and development of deucravacitinib in treating plaque psoriasis and potentially other TYK2-mediated diseases.