title: Diarylsulfonamides as selective, non-peptidic thrombin inhibitors.
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 microM 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.
authors.affiliation: Pharmazeutisch-Chemisches Institut der Universität, Heidelberg, Germany.
authors.forename: I R
authors.initials: IR
authors.lastname: Weber
authors.forename: R
authors.initials: R
authors.lastname: Neidlein
authors.forename: W
authors.initials: W
authors.lastname: von der Saal
authors.forename: F
authors.initials: F
authors.lastname: Grams
authors.forename: H
authors.initials: H
authors.lastname: Leinert
authors.forename: K
authors.initials: K
authors.lastname: Strein
authors.forename: R A
authors.initials: RA
authors.lastname: Engh
authors.forename: R
authors.initials: R
authors.lastname: Kucznierz
mesh_terms: D000991:Antithrombins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D000991:Antithrombins; D013449:Sulfonamides