Simple approach to the synthesis of novel tricyclic BACE1 inhibitor warhead through β-lactam opening

被引：5

作者：

Abed, Hassen Bel ^{[1
]}

Van Brandt, Sven F. A. ^{[1
]}

Antonio Vega, Juan ^{[2
]}

Gijsen, Harrie J. M. ^{[1
]}

机构：

[1] Janssen Res & Dev, Neurosci Med Chem, B-2340 Beerse, Belgium

[2] Janssen Res & Dev, Neurosci Med Chem, Poligono Ind, Toledo 45007, Spain

来源：

TETRAHEDRON LETTERS | 2015年 / 56卷 / 26期

关键词：

Alzheimer; beta-Lactam; BACE1; Tetrahydrofuran; Amidine; ALZHEIMERS-DISEASE; PROGRESS; MITSUNOBU; THERAPY; PROTEIN; DESIGN;

D O I：

10.1016/j.tetlet.2015.05.017

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A novel methodology for the synthesis of potential beta-secretase 1 (BACE-1) inhibitors has been elaborated from a beta-lactam precursor obtained by a Staudinger reaction. Ring opening of the beta-lactam gave access to a key intermediate trisubstituted tetrahydrofuran after a sequential reduction/Mitsunobu etherification. This strategy allowed a partial control of the stereochemistry through epimerization of the beta-lactam. Finally, the amidine was further modified by introducing an amide linker in order to deliver a putative BACE-1 inhibitor. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：4028 / 4030

页数：3

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