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
收藏
页码：4028 / 4030
页数：3
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