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Discovery of an Extremely Potent Thiazine-Based beta-Secretase Inhibitor with Reduced Cardiovascular and Liver Toxicity at a Low Projected Human Dose
Genetic evidence points to deposition of amyloid-beta (A beta) as a causal factor for Alzheimer’s disease. A beta generation is initiated when beta-secretase (BACE1) cleaves the amyloid precursor protein. Starting with an oxazine lead 1, we describe the discovery of a thiazine-based BACE1 inhibitor 5 with robust A beta reduction in vivo at low concentrations, leading to a low projected human dose of 14 mg/day where 5 achieved sustained A beta reduction of 80% at trough level.
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Reference:
Thiazine – an overview | ScienceDirect Topics,
,Thiazine | C4H5NS – PubChem