Novel acylguanidine containing thrombin inhibitors with reduced basicity at the P1 moiety

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 24, 1998, Pages 3603-3608

  Adang, Anton E P ^a   Lucas, Hans ^a   De Man, Adrianus P A ^a   Engh, Richard A ^b   Grootenhuis, Peter D J ^a  

^a NV ORGANON   (Netherlands)

^b MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

3 AMINO 2 PYRIDINONE DERIVATIVE; ACYLGUANIDINE DERIVATIVE; THROMBIN; THROMBIN INHIBITOR; TRYPSIN; UNCLASSIFIED DRUG;

ANTICOAGULATION; ARTICLE; CHEMICAL MODIFICATION; DRUG POTENCY; DRUG SELECTIVITY; STRUCTURE ACTIVITY RELATION; THROMBOGENICITY;

ANTITHROMBINS; GUANIDINE; STRUCTURE-ACTIVITY RELATIONSHIP; THROMBIN; TRYPSIN;

EID: 0032535563     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00650-7     Document Type: Article

References (18)

1. 1. Lumma, W. C.; Witherop, K. M.; Tucker, T. J.; Brady, S. F.; Sisko, J. T.; Naylor-Olsen, A. M.; Lewis, S. D.; Lucas, B. J.; Vacca, J. P. J. Med. Chem. 1998, 41, 1011.
2. 2. Wiley, M. R.; Fisher, M. J. Exp. Opin. Ther. Patents 1997, 7, 1265.
3. 3. Kimball, S. D. Blood Coagul. Fibrin. 1995, 6, 511.
4. 4. Ripka, W. C.; Vlasuk, G. P. Annu. Rep. Med. Chem. 1997, 32, 71.
5. 5. Tucker, T. J.; Lumma, W. C.; Lewis, S. D.; Gardell, S. J.; Lucas, B. J.; Baskin, E. P.; Woltmann, R. J. Med. Chem. 1997, 40, 1565.
6. 6. Teger-Nilsson, A.; Bylund, R.; Gustafsson, D.; Gyzander, E.; Eriksson, U. Thromb. Res. 1997, 85, 133.
7. 7. Stanton, J. L.; Gruenfeld, N.; Babiarz, J. E.; Ackerman, M. H.; Friedman, R. C. J. Med. Chem. 1983, 26, 1267.
8. 8.(a) Jetten, M.; Peters, C.; Visser, A.; Grootenhuis, P. D. J.; van Nispen, J. W.; Ottenheijm, H. C. J. Bioorg. Med. Chem. 1995, 3, 1099.
9. i.
10. 9. Engh, R. A.; Brandstetter, H.; Sucher, G.; Eichinger, A.; Baumann, U.; Bode, W.; Huber, R.; Poll, T.; Rudolph, R.; von der Saal, W. Structure 1996, 4, 1353.
11. 10. Schmid, A.; Scholz, W.; Lang, H. J.; Popp, R. Biochem Biophys. Res. Comm. 1992, 184, 112.
12. 11. Lyle, T. A.; Chen, Z.; Appleby, S. D.; Freidinger, R. M.; Gardell, S. J.; Lewis, S. D.; Li, Y.; Lyle, E. A.; Lynch, J. J.; Mulichak, A. M.; Ng, A. S.; Naylor-Olsen, A. M.; Sanders, W. M. Bioorg. Med. Chem. Lett. 1997, 7, 67.
13. 12. (a) Feng, D-M.; Gardell, S. J.; Lewis, S. D.; Bock, M. G.; Chen, Z.; Freidinger, R. M. J. Med. Chem. 1997, 40, 3726.
14. (b) Misra, R.; Kelly, Y.; Broun, B.; Roberts, D.; Chong, S.; Seiler, S. Bioorg. Med. Chem. Lett. 1994, 4, 2165.
15. (c) Eli Lilly, US-5707966, 1998.
16. 13. Synthelabo, EP-718307, 1996.
17. 14. Perrin, D. D. In Dissociation Constants of Organic Bases in Aqueous Solution; Butterworths: London, 1965; p 473.
18. 15. Andisik, D. W.; Bernstein, P. R.; Bryant, C. B.; Ceccarelli, C.; Damewood, J. R.; Edwards, P. D. J. Med. Chem. 1994, 37, 1259.