| Literature DB >> 19963375 |
Andreas Lerchner1, Rainer Machauer, Claudia Betschart, Siem Veenstra, Heinrich Rueeger, Clive McCarthy, Marina Tintelnot-Blomley, Anne-Lise Jaton, Sabine Rabe, Sandrine Desrayaud, Albert Enz, Matthias Staufenbiel, Paolo Paganetti, Jean-Michel Rondeau, Ulf Neumann.
Abstract
A series of macrocyclic peptidic BACE-1 inhibitors was designed. While potency on BACE-1 was rather high, the first set of compounds showed poor brain permeation and high efflux in the MDRI-MDCK assay. The replacement of the secondary benzylamino group with a phenylcyclopropylamino group maintained potency on BACE-1, while P-glycoprotein-mediated efflux was significantly reduced and brain permeation improved. Several compounds from this series demonstrated acute reduction of Abeta in human APP-wildtype transgenic (APP51/16) mice after oral administration. Copyright 2009 Elsevier Ltd. All rights reserved.Entities:
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Year: 2009 PMID： 19963375 DOI： 10.1016/j.bmcl.2009.11.092
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823