Synthesis Of Two Imidazole Cytokine Inhibitors Labelled With Carbon-14

Cytokines are protein hormones that regulate immune and inflammatory responses. Compounds I and 2 represented novel synthetic targets of potential interest as cytokine-supressing anti-inflammatory drugs. High and moderate specific activity C-14-labelled analogs were needed for drug metabolism, pharmacokinetic and formulation studies.The key isonitrile synthetic precursor 3 was a common intermediate in the preparation of both radiolabelled analogs. This intermediate was efficiently produced in five stages in 33% overall radiochemical yield from (KCN)-C-14. Compound I was produced in one step from the isonitrile, while 2 required two steps. The synthetic methodology leading to 3 in C-14-labelled form and the sequences leading to structures 1 and 2 are presented. Targets I and 2 were obtained in high radiochemical purity and specific activity.