Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and Efficacious γ-Secretase Inhibitors

Discovery of a series of pyrazolopiperidine sulfonamide based γ-secretase inhibitors and its SAR evolution is described. Significant increases in APP potency on the pyrazolopiperidine scaffold over the original N-bicyclic sulfonamide scaffold were achieved and this potency increase translated in an improved in vivo efficacy.