SF-11 is a selective, brain-penetrant NPY Y2 receptor antagonist with an IC50 value of 190 nM. Systematically explore the SAR of the hit molecule SF-11 that leads to the identification of selective and highly potent small molecule NPY Y2 receptor antagonist CYM 9484 (Compound 16). CYM 9484 is 10-fold more potent than the hit molecule SF-11. CYM 9484 is prepared by the coupling of α,α-diphenylpiperidino-4-methanol with a variety of aryl isothiocyanates.