| Literature DB >> 20005099 |
Matthew G Stanton1, Jed Hubbs, David Sloman, Christopher Hamblett, Paula Andrade, Minilik Angagaw, Grace Bi, Regina M Black, Jamie Crispino, Jonathan C Cruz, Eric Fan, Georgia Farris, Bethany L Hughes, Candia M Kenific, Richard E Middleton, George Nikov, Peter Sajonz, Sanjiv Shah, Nirah Shomer, Alexander A Szewczak, Flobert Tanga, Matthew T Tudge, Mark Shearman, Benito Munoz.
Abstract
We report herein a novel series of difluoropiperidine acetic acids as modulators of gamma-secretase. Synthesis of 2-aryl-3,3-difluoropiperidine analogs was facilitated by a unique and selective beta-difluorination with Selectfluor. Compounds 1f and 2c were selected for in vivo assessment and demonstrated selective lowering of Abeta42 in a genetically engineered mouse model of APP processing. Moreover, in a 7-day safety study, rats treated orally with compound 1f (250mg/kg per day, AUC(0-24)=2100microMh) did not exhibit Notch-related effects. Copyright 2009 Elsevier Ltd. All rights reserved.Entities:
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Year: 2009 PMID： 20005099 DOI： 10.1016/j.bmcl.2009.11.034
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823