Triazolyl tryptoline derivatives as β-secretase inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:20

Article

Jiaranaikulwanitch, Jutamas¹  Boonyarat, Chantana²  Fokin, Valery V.³  Vajragupta, Opa¹ 

[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

关键词: BACE1;    BACE1 inhibitor;    JJCA-140;    Tryptoline;    Docking;    Binding mode;    Enzyme assay;    Cathepsin-D;   

DOI  :  10.1016/j.bmcl.2010.09.043

来源: Elsevier

【 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.

【 授权许可】

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