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P2 '-truncated BACE-1 inhibitors with a novel hydroxethylene-like core
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2010 (English)In: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 45, no 2, 542-554 p.Article in journal (Refereed) Published
Abstract [en]

Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2' amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-I IC50 value of 140 nM. The synthesis of these BACE-I inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields.

Place, publisher, year, edition, pages
2010. Vol. 45, no 2, 542-554 p.
Keyword [en]
BACE-1, BACE, beta-Secretase, Asp2, Memapsin, PI
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-137520DOI: 10.1016/j.ejmech.2009.10.041ISI: 000274773300016PubMedID: 19995674OAI: oai:DiVA.org:uu-137520DiVA: diva2:378226
Available from: 2010-12-15 Created: 2010-12-15 Last updated: 2010-12-15Bibliographically approved

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