Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1378856 | Bioorganic & Medicinal Chemistry Letters | 2006 | 5 Pages |
Abstract
The structural features contributing to the different pharmacokinetic properties of the TACE/MMP inhibitors TNF484 and TrocadeTM were analyzed using an in vivo cassette-dosing approach in rats. This enabled us to identify a new lead compound with excellent pharmacokinetic properties, but weaker activity on the biological targets. Directed structural modifications maintained oral bioavailability and restored biological activity, leading to a novel compound almost equipotent to TNF484 in vivo, but with a more than tenfold higher oral bioavailability.
Graphical abstractTenfold improvement of the oral bioavailability of TNF484 with the help of cassette-dosing is described.Figure optionsDownload full-size imageDownload as PowerPoint slide
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Philipp Janser, Ulf Neumann, Wolfgang Miltz, Roland Feifel, Thomas Buhl,