Rational Design and Synthesis of Potent Dibenzazepine Motifs as β-Secretase Inhibitors

详细信息    查看全文

• 作者：Taleb H. Al-Tel ; Raed A. Al-Qawasmeh ; Marco F. Schmidt ; Amal Al-Aboudi ; Shashidhar N. Rao ; Salim S. Sabri ; Wolfgang Voelter
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：October 22, 2009
• 年：2009
• 卷：52
• 期：20
• 页码：6484-6488
• 全文大小：814K
• 年卷期：v.52,no.20(October 22, 2009)
• ISSN：1520-4804

文摘

We have identified small-molecule dibenzazepine inhibitors of β-secretase (BACE1). These BACE1 inhibitors possess two key salient features. The first is a seven-membered heterocyclic ring fused to two aromatic rings representing the P3−P2 residues. The second is an amide and/or amide bioisostere representing the P1′ residue. Rational optimization led to the identification of potent analogues, such as 10 (K_I = 211 nM).