Title of article :
A cassette-dosing approach for improvement of oral bioavailability of dual TACE/MMP inhibitors
Author/Authors :
Philipp Janser، نويسنده , , Ulf Neumann، نويسنده , , Wolfgang Miltz، نويسنده , , Roland Feifel، نويسنده , , Thomas Buhl، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2006
Pages :
5
From page :
2632
To page :
2636
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.
Keywords :
Trocade , Claisen–Ireland rearrangement , TNF? , TACE , MMP , TNF484 , metalloproteinase , inhibitor , Dual , Pharmacokinetics , Cassette-dosing , bioavailability , oral , Clearance , Absorption , rheumatoid arthritis
Journal title :
Bioorganic & Medicinal Chemistry Letters
Serial Year :
2006
Journal title :
Bioorganic & Medicinal Chemistry Letters
Record number :
796837
Link To Document :
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