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Design, Synthesis, and Evaluation of a Novel Series of Oxadiazine Gamma Secretase Modulators for Familial Alzheimer?s Disease
Herein we describe the design, synthesis, and evaluation of a novel series of oxadiazine-based gamma secretase modulators obtained via isosteric amide replacement and critical consideration of conformational restriction. Oxadiazine lead 47 possesses good in vitro potency with excellent predicted CNS drug-like properties and desirable ADME/PK profile. This lead compound demonstrated robust Abeta42 reductions and subsequent Abeta37 increases in both rodent brain and CSF at 30 mg/kg dosed orally.
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Reference£º
Oxazolidine – Wikipedia,
Oxazolidine | C3H2290NO – PubChem