Author/Authors :
Ingo R. Weber، نويسنده , , Richard Neidlein، نويسنده , , Rainer Rudolph and Wolfgang von der Saal، نويسنده , , Frank Grams، نويسنده , , Herbert Leinert، نويسنده , , Klaus Strein، نويسنده , , Richard A. Engh، نويسنده , , Ralf Kucznierz، نويسنده ,
Abstract :
Based on the structures of aminopyridine thrombin inhibitors (1), a series of aminoalkyl- and guanidinoalkyl-substituted diarylsulfonamides were prepared. The most potent derivative, N-[3-(4-guanidinobutoxy)-5-methyl-phenyl]-benzenesulfonamide (6c) had Ki = 0.18 μM for thrombin and did not inhibit trypsin, plasmin, or factor Xa. Comparison of the X-ray structures of the thrombin/1b and the thrombin/6c complexes revealed important aspects which govern the binding of such diarylsulfonamides to thrombin.
