Diarylsulfonamides as selective, non-peptidic thrombin inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 13, 1998, Pages 1613-1618

  Weber, Ingo R ^a   Neidlein, Richard ^a   Von Der Saal, Wolfgang ^b   Grams, Frank ^b   Leinert, Herbert ^b   Strein, Klaus ^b   Engh, Richard A ^c   Kucznierz, Ralf ^b  

^a Pharmazeutisch Chemisches I der U   (Germany)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

^c MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BLOOD CLOTTING FACTOR 10; N [3 (4 GUANIDINOBUTOXY) 5 METHYLPHENYL]BENZENESULFONAMIDE; PLASMIN; SULFONAMIDE; THROMBIN INHIBITOR; TRYPSIN; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION KINETICS; CRYSTAL STRUCTURE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; THROMBIN TIME;

ANTITHROMBINS; MOLECULAR STRUCTURE; SULFONAMIDES; X-RAY DIFFRACTION;

EID: 0032493403     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00269-8     Document Type: Article

References (11)

1. 1. Part of the Ph.D. thesis of Ingo R. Weber, University of Heidelberg, 1997.
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8. 8. The boro-arginine based thrombin inhibitor DuP 714 has Ki = 0.04 nM, while its boro-lysine derivative has Ki = 0.24 nM: Caccialo, J.; Fevig, J. M.; Alexander, R. S.; Brittelli, D. R.; Kettner, C. A.; Knabb, R. M.; Weber, P. C. Bioorg. Med. Chem. Lett. 1996, 6, 301.
9. 9. von der Saal, W.; unpublished results.
10. 10. Brandstetter, H.; Turk, D.; Hoeffken, H. W.; Grosse, D.; Stürzebecher, J.; Martin, P. D.; Edwards, B. F.; Bode, W. J. Mol. Biol. 1992, 226, 1085.
11. 11. For the modelling study, the guanidino group was fixed in the position it occupies in the thrombin / 6c complex, and the central tolyl group was fixed in its position of the thrombin / 1b complex. Both residues were connected via a butyl chain.