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

被引：50

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

[1]

Amgen Inc, 2011, WO, Patent No. [2011115928, WO2011115928A1]

[2]

Badiger S., 2011, [No title captured], Patent No. [WO2011009943 A1, 2011009943, W02011009943]

[3]

Banner D., 2010, WO-2010/128058, Patent No. [WO2010128058, 2010128058]

[4]

Clark C. T., 2011, [No title captured], Patent No. [W02011123674A1, 2011123674, WO 2011123674A1]

[5] SYNTHESIS OF 2-AMINO-5,6-DIHYDRO-4H-1,3-THIAZINES AND RELATED COMPOUNDS BY ACID-CATALYZED CYCLIZATION OF ALLYLIC ISOTHIURONIUM SALTS [J].

COHEN, N ;

BANNER, BL .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1977, 14 (05) :717-723

[6]

Cole DC, 2010, METH PRIN MED CHEM, V45, P481

[7] Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor [J].

Cumming, Jared N. ;

Smith, Elizabeth M. ;

Wang, Lingyan ;

Misiaszek, Jeffrey ;

Durkin, James ;

Pan, Jianping ;

Iserloh, Ulrich ;

Wu, Yusheng ;

Zhu, Zhaoning ;

Strickland, Corey ;

Voigt, Johannes ;

Chen, Xia ;

Kennedy, Matthew E. ;

Kuvelkar, Reshma ;

Hyde, Lynn A. ;

Cox, Kathleen ;

Favreau, Leonard ;

Czarniecki, Michael F. ;

Greenlee, William J. ;

McKittrick, Brian A. ;

Parker, Eric M. ;

Stamford, Andrew W. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (07) :2444-2449

[8] A practical entry to β-aryl-β-alkyl amino alcohols: application to the synthesis of a potent BACE1 inhibitor [J].

Delgado, Oscar ;

Monteagudo, Antonio ;

Van Gool, Michiel ;

Trabanco, Andres A. ;

Fustero, Santos .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2012, 10 (33) :6758-6766

[9]

Dimopoulos P., 2012, Patent No. [WO /2012/093148, 2012093148, WO2012093148]

[10]

Eisai R&D management co. LTD, 2011, WO, Patent No. [2011009898, WO2011009898]

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