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Inhibitors of Aβ production: solid-phase synthesis and SAR of α-hydroxycarbonyl derivatives

2003; Elsevier BV; Volume: 13; Issue: 6 Linguagem: Inglês

10.1016/s0960-894x(02)01058-2

1464-3405

Owen B. Wallace, David W. Smith, Milind Deshpande, Craig Polson, Kevin M. Felsenstein,

Computational Drug Discovery Methods

Inhibitors of amyloid-β (Aβ) protein production have been widely pursued as a potential treatment for Alzheimer's disease. Following the identification of a 5 μM screening hit, SAR was initiated using solid-phase synthetic techniques. Two series of α-hydroxy esters and ketones which are sub-micromolar inhibitors of Aβ production were identified. The most potent α-hydroxyketone identified is approximately 30-fold more potent than the initial lead.