| Literature DB >> 23590342 |
Hans Hilpert1, Wolfgang Guba, Thomas J Woltering, Wolfgang Wostl, Emmanuel Pinard, Harald Mauser, Alexander V Mayweg, Mark Rogers-Evans, Roland Humm, Daniela Krummenacher, Thorsten Muser, Christian Schnider, Helmut Jacobsen, Laurence Ozmen, Alessandra Bergadano, David W Banner, Remo Hochstrasser, Andreas Kuglstatter, Pascale David-Pierson, Holger Fischer, Alessandra Polara, Robert Narquizian.
Abstract
An extensive fluorine scan of 1,3-oxazines revealed the power of fluorine(s) to lower the pKa and thereby dramatically change the pharmacological profile of this class of BACE1 inhibitors. The CF3 substituted oxazine 89, a potent and highly brain penetrant BACE1 inhibitor, was able to reduce significantly CSF Aβ40 and 42 in rats at oral doses as low as 1 mg/kg. The effect was long lasting, showing a significant reduction of Aβ40 and 42 even after 24 h. In contrast to 89, compound 1b lacking the CF3 group was virtually inactive in vivo.Entities:
Mesh：
Substances：
Year: 2013 PMID： 23590342 DOI： 10.1021/jm400225m
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446