Synthesis of 3 H, 13 C2 , 2 H414 C-SCH 430765 and 35 S-SCH 500946, potent and selective inhibitors of the NPY5 receptor

SCH 430765 and SCH 500496 are potent and selective antagonists of the NPY₅ receptor. NPY₅ receptor antagonists have the potential for the treatment of obesity. [³⁵ S]SCH 500946 was prepared for a competition binding assay which led to the identification of SCH 430765. Three distinct isotopically labelled forms of SCH 430765 were synthesized. [³ H]SCH 430765 was prepared for a preliminary absorption, distribution, metabolism and excretion data evaluation of the compound and [¹⁴ C]SCH 430765 for more definitive absorption, distribution, metabolism and excretion data work. In addition, [¹³ C₂ ,² H₄ ]SCH 430765 was prepared as an internal standard for a LC-MS bioanalytical method. The paper discusses the synthesis of 3 isotopically labelled forms of SCH 430765 and [³⁵ S]SCH 500946.