Triazolyl tryptoline derivatives as β-secretase inhibitors

被引：21

作者：

Jiaranaikulwanitch, Jutamas ^{[1
]}

Boonyarat, Chantana ^{[2
]}

Fokin, Valery V. ^{[3
]}

Vajragupta, Opa ^{[1
]}

机构：

[1] Mahidol Univ, Fac Pharm, Dept Pharmaceut Chem, Bangkok 10400, Thailand

[2] Khon Kaen Univ, Fac Pharmaceut Sci, Khon Kaen 40002, Thailand

[3] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 22期

关键词：

BACE1; inhibitor; JJCA-140; Tryptoline; Docking; Binding mode; Enzyme assay; Cathepsin-D; ALZHEIMERS-DISEASE; EFFICIENCY INDEXES; LIGAND EFFICIENCY; DRUG DISCOVERY; DESIGN; BACE-1;

D O I：

10.1016/j.bmcl.2010.09.043

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Tryptoline, a core structure of ochrolifuanine E, which is a hit compound from virtual screening of the Thai herbal database against BACE1 was used as a scaffold for the design of BACE1 inhibitors. The tryptoline was linked with different side chains by 1,2,3-triazole ring readily synthesized by catalytic azide-alkyne cycloaddition reactions. Twenty two triazolyl tryptoline derivatives were synthesized and screened for the inhibitory action against BACE1. JJCA-140 was the most potent inhibitor (IC(50) = 1.49 mu M) and was 100 times more selective for BACE1 than for Cat-D. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6572 / 6576

页数：5

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