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

被引：39

作者：

Al-Tel, Taleb H. ^{[1
]}

Al-Qawasmeh, Raed A. ^{[2
]}

Schmidt, Marco F. ^{[3
]}

Al-Aboudi, Amal ^{[2
]}

Rao, Shashidhar N. ^{[4
]}

Sabri, Salim S. ^{[1
]}

Voelter, Wolfgang ^{[5
]}

机构：

[1] Univ Sharjah, Coll Pharm, Sharjah, U Arab Emirates

[2] Univ Jordan, Dept Chem, Amman 1194, Jordan

[3] Leibniz Inst Mol Pharmacol FMP, D-13125 Berlin, Germany

[4] Schrodinger, New York, NY 10036 USA

[5] Univ Tubingen, Interfak Inst Biochem, D-72076 Tubingen, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 20期

关键词：

ALZHEIMERS-DISEASE; BACE1; INHIBITORS; DISCOVERY; PROGRESS; DRUG;

D O I：

10.1021/jm9008482

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have identified small-molecule dibenzazepine. inhibitors of beta-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-1 = 211 nM).

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收藏

页码：6484 / 6488

页数：5

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