Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (β-secretase)

被引：77

作者：

Ghosh, AK

Devasamudram, T

Hong, L

DeZutter, C

Xu, XM

Weerasena, V

Koelsch, G

Bilcer, G

Tang, J

机构：

[1] Zapaq Inc, Oklahoma City, OK 73104 USA

[2] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Prot Studies Program, Oklahoma City, OK 73104 USA

[3] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 01期

关键词：

Alzheimer's disease; inhibitor; memapsin; 2; secretase;

D O I：

10.1016/j.bmcl.2004.10.084

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel macrocyclic amide-urethanes was designed and synthesized based upon the X-ray crystal structure of our lead inhibitor (1, OM99-2 with eight residues) bound to memapsin 2. Ring size and substituent effects have been investigated. Cycloamide-urethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against human brain memapsin 2 (beta-secretase). (C) 2004 Elsevier Ltd. All rights reserved.

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页码：15 / 20

页数：6

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