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Synthesis of potent beta-secretase inhibitors containing a hydroxyethylamine dipeptide isostere and their structure-activity relationship studies.

作者信息

Tamamura Hirokazu, Kato Terukazu, Otaka Akira, Fujii Nobutaka

机构信息

Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.

出版信息

Org Biomol Chem. 2003 Jul 21;1(14):2468-73. doi: 10.1039/b304842j.

DOI:10.1039/b304842j
PMID:12956063
Abstract

Several beta-secretase inhibitors were designed based on hydroxyethylamine dipeptide isostere (HDI) structures and were synthesized by a methodology using the aza-Payne rearragement and O,N-acyl transfer reactions to study their structure-activity relationships. Among these pseudopeptides, effective compounds were developed as the first beta-secretase inhibitors containing the HDI transition state mimic with potent enzyme inhibitory activity (IC50 < 100 nM).

摘要

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