Synthesis and SAR of bis-statine based peptides as BACE 1 inhibitors |
| |
Authors: | Hu Baihua Fan Kristi Yi Bridges Kristie Chopra Rajiv Lovering Frank Cole Derek Zhou Ping Ellingboe John Jin Guixiang Cowling Rebecca Bard Jonathan |
| |
Affiliation: | Department of Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. hub@wyeth.com |
| |
Abstract: | A new series of bis-statine based peptidomimetic inhibitors of human beta-secretase (BACE 1) was developed by structure-based modification of the three regions to the initial lead 3: an N-terminus, a central bis-statine core, and a C-terminus. Introduction of a 4-aminomethylbenzoic acid on the C-terminus resulted in a potent BACE 1 inhibitor with an IC50 value of 21 nM. The general requirements for the optimal substrate-enzyme interaction are disclosed herein. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|