Development of BACE1 Inhibitors for Alzheimer's Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. The production and accumulation of β-amyloid peptides (Aβ) from the β-amyloid precursor protein (APP) are believed to play a key role in the onset and progression of AD. BACE1 (β-site APP cleaving enzyme 1) is the protease responsible for the N-terminal cleavage of APP leading to the production of Aβ peptides and the development of BACE1 inhibitors as potential therapeutic agents for AD has generated tremendous interests from both academia and the pharmaceutical industry. A wide variety of BACE1 inhibitors have been reported, several of which have demonstrated highly promising efficacy in animal models of AD. This review focuses on recent disclosures of BACE1 inhibitors in the patent and scientific literature, covering the period from approximately May 2004 to November 2005.