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Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors

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Authors
Xu, W.
Chen, G.
Zhu, W.
Zuo, Zhili
Date
2010
Type
Journal Article

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Xu, Weijun and Chen, Gang and Zhu, Weiliang and Zuo, Zhili. 2010. Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors. Bioorganic & Medicinal Chemistry Letters. 20 (21): pp. 6203-6207.
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Bioorganic & Medicinal Chemistry Letters
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School of Biomedical Sciences
Remarks

NOTICE: This is the author’s version of a work that was accepted for publication in Bioorganic & Medicinal Chemistry Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes mayhave been made to this work since it was submitted for publication. A definitive version was subsequently published in Bioorganic & Medicinal Chemistry Letters [20, 21, 2010] DOI 10.1016/j.bmcl.2010.08.111

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Abstract

A similarity search on the structural analogs of an inhibitor of BACE-1 with IC50 2.8 μM, which contained a P1 benzothiazole group together with a triazine ring linked by a secondary amine group, was described in this Letter and some more potent inhibitors against BACE-1 were identified. The most potent compound 5 (IC50 = 0.12 μM) increases the inhibitory potency by 24 folds. Our results suggest that a pyrrolidinyl side group at the P3′ and P4′ of the inhibitors are favored for strong inhibition and a small aromatic group at the P4 position is also essential to the potency.