Guo Tao, Hobbs Doug W
Pharmacopeia Drug Discovery, Inc., Box 5350, Princeton, NJ 08543-5350, USA.
Curr Med Chem. 2006;13(15):1811-29. doi: 10.2174/092986706777452489.
Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. The production and accumulation of beta-amyloid peptides (Abeta) from the beta-amyloid precursor protein (APP) are believed to play a key role in the onset and progression of AD. BACE1 (beta-site APP cleaving enzyme 1) is the protease responsible for the N-terminal cleavage of APP leading to the production of Abeta 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.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，也是痴呆最常见的病因。据信，β-淀粉样前体蛋白（APP）产生和积累β-淀粉样肽（Aβ）在AD的发病和进展中起关键作用。β-分泌酶1（BACE1）是负责APP N端切割从而导致Aβ肽产生的蛋白酶，开发BACE1抑制剂作为AD的潜在治疗药物引起了学术界和制药行业的极大兴趣。已经报道了各种各样的BACE1抑制剂，其中几种在AD动物模型中已显示出非常有前景的疗效。本综述重点关注2004年5月至2005年11月期间专利和科学文献中有关BACE1抑制剂的最新披露情况。
