Bioorganic & Medicinal Chemistry Letters 2003-03-24

Inhibitors of Abeta production: solid-phase synthesis and SAR of alpha-hydroxycarbonyl derivatives.

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

Index: Bioorg. Med. Chem. Lett. 13(6) , 1203-6, (2003)

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Abstract

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