Identification of positron emission tomography ligands for NPY Y5 receptors in the brain

Abstract A series of trans -3-oxospiro[(aza)isobenzofuran-1(3 H ),1′-cyclohexane]-4′-carboxamide derivatives were synthesized and profiled for NPY Y5 binding affinity, brain and CSF penetrability in rats, and susceptibility to human and mouse P-glycoprotein transporters in order to develop a PET ligand. Compound 12b exhibited an acceptable profile for a PET ligand, and [ 11 C] 12b was successfully utilized in clinical settings as a Y5 PET ligand.