Discovery of a Potent Pyrazolopyridine Series of γ-Secretase Modulators

The synthesis and structure−activity relationship of a novel series of pyrazolopyridines are reported. These compounds represent a new class of γ-secretase modulators that demonstrate good in vitro potency in inhibiting Aβ42 production. Examples with statistically significant in vivo efficacy in reducing the production of rat cerebrospinal fluid Aβ42 were also identified.