BACE1 inhibitors: A head group scan on a series of amides

被引：49

作者：

Woltering, Thomas J. ^{[1
]}

Wostl, Wolfgang ^{[1
]}

Hilpert, Hans ^{[1
]}

Rogers-Evans, Mark ^{[1
]}

Pinard, Emmanuel ^{[1
]}

Mayweg, Alexander ^{[1
]}

Goebel, Martin ^{[1
]}

Banner, David W. ^{[1
]}

Benz, Joerg ^{[1
]}

Travagli, Massimiliano ^{[2
]}

Pollastrini, Martina ^{[2
]}

Marconi, Guido ^{[2
]}

Gabellieri, Emanuele ^{[2
]}

Guba, Wolfgang ^{[1
]}

Mauser, Harald ^{[1
]}

Andreini, Matteo ^{[2
]}

Jacobsen, Helmut ^{[1
]}

Power, Eoin ^{[2
]}

Narquizian, Robert ^{[1
]}

机构：

[1] F Hoffmann Roche Ltd, Pharma Res, CH-4070 Basel, Switzerland

[2] Siena Biotech SpA, I-53100 Siena, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 14期

关键词：

BACE1; Alzheimer's disease; Inhibitors; pK(a); P-gp; BETA; DESIGN;

D O I：

10.1016/j.bmcl.2013.05.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of amides bearing a variety of amidine head groups was investigated as BACE1 inhibitors with respect to inhibitory activity in a BACE1 enzyme as well as a cell-based assay. Determination of their basicity as well as their properties as substrates of P-glycoprotein revealed that a 2-amino-1,3-oxazine head group would be a suitable starting point for further development of brain penetrating compounds for potential Alzheimer's disease treatment. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：4239 / 4243

页数：5

共 31 条

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