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

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 po...

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Main Authors: Xu, W., Chen, G., Zhu, W., Zuo, Zhili
Format: Journal Article
Published: Pergamon 2010
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/48140
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author Xu, W.
Chen, G.
Zhu, W.
Zuo, Zhili
author_facet Xu, W.
Chen, G.
Zhu, W.
Zuo, Zhili
author_sort Xu, W.
building Curtin Institutional Repository
collection Online Access
description 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.
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institution Curtin University Malaysia
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publishDate 2010
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spelling curtin-20.500.11937-481402019-02-19T04:26:47Z Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors Xu, W. Chen, G. Zhu, W. Zuo, Zhili FRET Virtual screening Bioassay BACE-1 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. 2010 Journal Article http://hdl.handle.net/20.500.11937/48140 10.1016/j.bmcl.2010.08.111 Pergamon fulltext
spellingShingle FRET
Virtual screening
Bioassay
BACE-1
Xu, W.
Chen, G.
Zhu, W.
Zuo, Zhili
Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors
title Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors
title_full Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors
title_fullStr Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors
title_full_unstemmed Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors
title_short Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors
title_sort molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic bace-1 inhibitors
topic FRET
Virtual screening
Bioassay
BACE-1
url http://hdl.handle.net/20.500.11937/48140