Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 15, Issue 1, Pages 15-20Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2004.10.084
Keywords
Alzheimer's disease; inhibitor; memapsin 2; secretase
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Funding
- NIA NIH HHS [AG 18933] Funding Source: Medline
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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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