Stereochemical analysis of (hydroxyethyl)urea peptidomimetic inhibitors of γ-secretase

被引：39
作者：
Bakshi, P
Wolfe, MS
机构：
[1] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 26期
关键词：
D O I：
10.1021/jm049566e
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
(Hydroxyethyl)urea peptidomimetics systematically altered at positions P2-P3' with hydrophobic D-amino acids were synthesized. An all D-amino acid containing analogue was identified that effectively blocked gamma-secretase activity in a cell-free system (IC50 = 30 nM). Systematic alteration of the stereocenters of a potent compound revealed interdependence between the various positions. Although typically less potent than their L-peptidomimetic counterparts. selected all D-amino acid containing analogues were equipotent. to their counterparts in a cell-based assay when incubated for extended times.
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收藏
页码：6485 / 6489
页数：5
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