Potent and efficacious thienylamidine-incorporated thrombin inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 13, 1998, Pages 1683-1686

  Lee, Koo ^a   Hwang, Sang Yeul ^a   Yun, Mikyung ^a   Kim, Dong Soo ^a  

^a LG Chemical Ltd   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

THROMBIN INHIBITOR;

ANTICOAGULATION; ARTICLE; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG SPECIFICITY; DRUG SYNTHESIS; VEIN THROMBOSIS;

ANIMALS; ANTITHROMBINS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; MOLECULAR STRUCTURE; RATS; SULFANILAMIDES; THROMBIN;

EID: 0032493485     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00293-5     Document Type: Article

References (19)

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8. 4. Na-(4-toluenesufonyl)-p-amidinophenylalanyl-piperidine: Markwardt, F.; Wagner, G; Sturzebecher, J.; Walsmann, P. Thromb. Res. 1980, 17, 425. Turk, D.; Sturzebecher, J.; Bode, W. FEBS Lett. 1991, 287, 133.
9. 4. Na-(4-toluenesufonyl)-p-amidinophenylalanyl-piperidine: Markwardt, F.; Wagner, G; Sturzebecher, J.; Walsmann, P. Thromb. Res. 1980, 17, 425. Turk, D.; Sturzebecher, J.; Bode, W. FEBS Lett. 1991, 287, 133.
10. 6 In addition, 2,4-substituted thienylamidine has been shown to be a better benzamidine surrogate in factor Xa inhibitors, cf.: Ewing, W. R. et al. 214th ACS National Meeting 1997, Las Vegas, NV, Abstract MEDI 50.
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13. 3b and data were refined to a crystallographic R-factor of 0.201.
14. 8. Similar speculation was made by the Merck group in their work on thrombin inhibitors, cf.: Feng, D.-M.; Gardell, S. J.; Lewis, S. D.; Bock, M. G.; Chen, Z.; Freidinger, R. M.; Naylor-Olsen, A. M.; Ramjit, H. G.; Woltmann, R.; Baskin, E. P.; Lynch, J. J.; Lucas, R.; Shafer, J. A.; Chen, I-W.; Dancheck, K. B.; Mao, S.-S.; Krueger, J. A.; Hare, T. R; Mulichak, A. M.; Vacca, J. P. J. Med. Chem. 1997, 40, 3726.
15. 9. A minimum of 3 rats was tested: Millet, J.; Theveniaux, J.; Brown, N. L. Thromb. Haemost. 1992, 76, 176.
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17. 11. The detailed assay conditions are described in ref 3a and 10.
18. 12. Sturzebecher, J.; Prasa, D.; Hauptmann, J.; Vieweg, H.; Wikstrom, P. J. Med. Chem. 1997, 40, 3091.
19. 13. Some 5-membered heterocyclic replacements other than the thiophene such as furan and thiazole resulted in a significant decrease in thrombin inhibitory potency, Lim, J. C.; Shin, Y.; Lee, K. unpublished results.