A small chemical library of 2-aminoimidazole derivatives as BACE-1 inhibitors: Structure-based design, synthesis, and biological evaluation

被引：28

作者：

Chiriano, Gianpaolo ^{[2
,3
]}

De Simone, Angela ^{[1
]}

Mancini, Francesca ^{[1
]}

Perez, Daniel I. ^{[4
]}

Cavalli, Andrea ^{[1
,5
]}

Bolognesi, Maria Laura ^{[1
]}

Legname, Giuseppe ^{[6
]}

Martinez, Ana ^{[4
]}

Andrisano, Vincenza ^{[1
]}

Carloni, Paolo ^{[7
]}

Roberti, Marinella ^{[1
]}

机构：

[1] Univ Bologna, Dept Pharmaceut Sci, I-40126 Bologna, Italy

[2] SISSA ISAS, Stat & Biol Phys Sect, I-34136 Trieste, Italy

[3] Italian Inst Technol, SISSA ISAS Unit, I-16163 Genoa, Italy

[4] CSIC, Inst Quim Med, E-28006 Madrid, Spain

[5] Italian Inst Technol, Dept Drug Discovery & Dev, I-16163 Genoa, Italy

[6] SISSA ISAS, Neurobiol Sect, I-34136 Trieste, Italy

[7] German Res Sch Simulat Sci GmbH, D-52425 Julich, Germany

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 48卷

关键词：

Alzheimer's disease; Amyloid-beta peptide; Drug design; Hit identification; 2-Aminoimidazole; MEMAPSIN-2; BETA-SECRETASE; ALZHEIMERS-DISEASE; GAMMA-SECRETASE; STRATEGIES; FAMILY; MODEL;

D O I：

10.1016/j.ejmech.2011.12.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In this work, we report a rational structure-based approach aimed at the discovery of new 2-aminoimidazoles as beta-secretase inhibitors. Taking advantage of a microwave-assisted synthetic protocol, a small library of derivatives was obtained and biologically evaluated. Two compounds showed promising activities in both enzymatic and cellular assays. Moreover, one of them exhibited the capability to cross the blood brain barrier as assessed by the parallel artificial membrane permeability assay. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：206 / 213

页数：8

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