Diarylsulfonamides as selective, non-peptidic thrombin inhibitors

Article abstract of DOI:10.1016/S0960-894X(98)00269-8

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 / 6e complexes revealed important aspects which govern the binding of such diarylsulfonamides to thrombin.