SYNTHESIS OF CARBON-14 LABELED SCH 351125, A CCR5 RECEPTOR ANTAGONIST

摘要

HIV infection leading to AIDS is a major cause of death worldwide. There is a continuing need for new therapy for this disease, especially against novel molecular targets.3 SCH 351125 is a potent, selective CCR5 antagonist currently in early clinical trials.1'2'1 [14C]SCH 351125 was needed for assessment of the ADME properties of this compound. We first report a convenient synthesis of l-benzyl-4-hydroxy[2-l4C]piperidine, starting from commercially available ~2% aqueous [14C]formaldehyde solution. Piperidines substituted in the 4 position are present in many marketed drugs, drug candidates and natural products, making this a useful isotopically labeled intermediate. Synthesis of [14C]SCH 351125 from l-benzyl-4-hydroxy[2-14C]piperidine is then discussed. SCH 351125 exists as a mixture of four atropisomers which can be separated by analytical chiral HPLC. Finally, crystallization of [14C]SCH 351125 as a besylate salt with the desired atropisomer composition is described.