Design, Synthesis and Docking Studies of Hydroxyethylamine and Hydroxyethylsulfide BACE-1 Inhibitors

被引：5

作者：

Rizzi, Luca ^{[1
]}

Vaiana, Nadia ^{[1
]}

Sagui, Francesca ^{[1
]}

Genesio, Eva ^{[2
]}

Pilli, Elena ^{[2
]}

Porcari, Valentina ^{[2
]}

Romeo, Sergio ^{[1
]}

机构：

[1] Univ Milan, Inst Med Chem Pietro Pratesi, Sch Pharm, I-20133 Milan, Italy

[2] Siena Biotech SpA, Dept Med Chem & Screening Sci 2, Siena, Italy

来源：

PROTEIN AND PEPTIDE LETTERS | 2009年 / 16卷 / 01期

关键词：

Alzheimer; hydrolases; BACE-1; inhibitors; hydroxyethylamine; hydroxyethylsulfide; HUMAN BETA-SECRETASE; ALZHEIMERS-DISEASE; HIV-1; PROTEASE; PEPTIDOMIMETIC INHIBITORS; CRYSTAL-STRUCTURE; IDENTIFICATION; COMPLEX; CONFIGURATION; ISOSTERE; BINDING;

D O I：

10.2174/092986609787049439

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Both stereoisomer of hydroxyethylamine (HEA) and hydroxyethylsulfide (HES) transition-state isostere inhibitors of BACE-1 were synthesized. The syn-HEA epimer resulted always more active than the anti stereoisomer independently from the P-1 and the P-1' substituents. On the contrary, the anti epimer of the HES isostere resulted more active than the syn stereoisomer. The change of stereopreference was studied by molecular modelling.

引用

页码：86 / 90

页数：5

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