Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 16, 2007, Pages 4568-4574

  Trujillo, John I ^a   Huang, Horng Chih ^a   Neumann, William L ^a   Mahoney, Matthew W ^a   Long, Scott ^a   Huang, Wei ^a   Garland, Danny J ^a   Kusturin, Carrie ^a   Abbas, Zaheer ^a   South, Michael S ^a   Reitz, David B ^a  

^a PFIZER INC   (United States)

Author keywords

Amidine; Anticoagulants; Antithrombotics; Factor VIIa; Oral; Pyrazinones; Serine protease; TF VIIa; Thrombosis

Indexed keywords

AMIDINE; ANTICOAGULANT AGENT; BENZENE DERIVATIVE; BLOOD CLOTTING FACTOR 7A INHIBITOR;

ARTICLE; DOSE RESPONSE; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; INTESTINE; IONIZATION; NONHUMAN; SUSTAINED RELEASE PREPARATION;

ANTICOAGULANTS; DRUG DESIGN; FACTOR VIIA; MOLECULAR STRUCTURE; PYRANS; STRUCTURE-ACTIVITY RELATIONSHIP; THROMBOPLASTIN;

EID: 34447313653     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.05.090     Document Type: Article

References (36)

1. Braunwald E., Califf R.M., Cannon C.P., Fox K.A., Fuster V., Gibler W.B., Harrington R.A., King S.B., Kleiman N.S., Theroux P., Topol E.J., Van de Werf F., White H.D., and Willerson J.T. Am. J. Med. 108 (2000) 41
2. Gage B.F., Fihn S.D., and White R.H. Am. J. Med. 109 (2000) 481
3. Hirsh J. Thromb. Res. 109 (2003) S1
4. Gresele P., and Agnelli G. Trends Pharmacol. Sci. 23 (2002) 25
5. For reviews in the area of TF-VIIa inhibitors, see:. Kranjc A., Kikelj D., and Peterlin-Masic L. Curr. Pharm. Des. 11 (2005) 4207
6. Lazarus R.A., Oliver A.G., Eigenbrot C., and Kirchofer D. Curr. Med. Chem. 11 (2004) 2275
7. Robinson L.A., and Saiah E. Ann. Rep. Med. Chem. 12 (2002) 85
8. Szalony J.A., Taite B.B., Girard T.J., Nicholson N.S., and LaChance R.M. J. Thromb. 14 (2002) 113
9. Zoldhelyi P., McNatt J., Shelat H.S., Yamamoto Y., Chen Z.-Q., and Willerson J.T. Circulation 101 (2000) 289
10. Himber J., Kirchhofer D., Riedereer M., Tschopp T.B., Steiner B., and Roux S.P. Thromb. Haemost. 7 (1997) 1142
11. Harker L.A., Hanson S.R., Wilcox J.N., and Kelly A.B. Haemostasis 26 (1996) 76
12. Parlow J.J., and South M.S. Tetrahedron 59 (2003) 7695
13. South M.S., Case B.L., Wood R.S., Jones D.E., Hayes M.J., Girard T.J., Lachance R.M., Nicholson N.S., Clare M., Stevens A.M., Stegeman R.A., Stallings W.C., Kurumbail R.G., and Parlow J.J. Bioorg. Med. Chem. Lett. 13 (2003) 2319
14. South M.S., Dice T.A., Girard T.J., Lachance R.M., Stevens A.M., Stegeman R.A., Stallings W.C., Kurumbail R.G., and Parlow J.J. Bioorg. Med. Chem. Lett. 13 (2003) 2363
15. Parlow J.J., Case B.L., Dice T.A., Fenton R.L., Hayes M.J., Jones D.E., Neumann W.L., Wood R.S., Lachance R.M., Girard T.J., Nicholson N.S., Clare M., Stegeman R.A., Stevens A.M., Stallings W.C., Kurumbail R.G., and South M.S. J. Med. Chem. 46 (2003) 4050
16. Parlow J.J., Stegeman R.A., Stevens A.M., Stallings W.C., Kurumbail R.G., and South M.S. J. Med. Chem. 46 (2003) 4297
17. Parlow J.J., Stegeman R.A., Stevens A.M., Stallings W.C., Kurumbail R.G., and South M.S. Bioorg. Med. Chem. Lett. 13 (2003) 3721
18. Parlow J.J., Dice T.A., Lachance R.M., Girard T.J., Stevens A.M., Stegeman R.A., Stallings W.C., Kurumbail R.G., and South M.S. J. Med. Chem. 46 (2003) 4043
19. Parlow J.J., Kurumbail R.G., Stegeman R.A., Stevens A.M., Stallings W.C., and South M.S. J. Med. Chem. 46 (2003) 4696
20. Parlow J.J., Stevens A.M., Stegeman R., Stallings W.C., Kurumbail R.G., and South M.S. J. Med. Chem. 46 (2003) 4297
21. Pinto D.J.P., Orwat M.J., Wang S., Fevig J.M., Quan M.L., Amparo E., Cacciola J., Rossi K.A., Alexander R.S., Smallwood A.M., Luettgen J.M., Liang L., Aungst B.J., Wright M.R., Knabb R.M., Wong P.C., Wexler R.R., and Lam P.Y.S. J. Med. Chem. 44 (2001) 566
22. Pauls H.W., and Ewing W.R. Curr. Top. Med. Chem. 1 (2001) 83
23. Schumacher W.A., Balasubramanian N., St. Laurent D.R., and Seiler S.M. Eur. J. Pharmacol. 259 (1994) 165
24. Hauptmann J., and Markwardt F. Semin. Thromb. Hemost. 18 (1992) 200
25. For a recent report of TF/FVIIa inhibitors with non-amidine P1 substituents, see:. Miura M., et al. Bioorg. Med. Chem. 14 (2006) 7688
26. Bioorg. Med. Chem. 15 (2007) 160
27. Eriksson U., Bredberg U., Hoffmann K., Thuresson A., Gabrielsson M., Ericsson H., Ahnoff M., Gislen K., Fager G., and Gustafsson D. Drug Metab. Dispos. 31 (2003) 29
28. Clement B. Drug Metab. Rev. 34 (2002) 565
29. Riggs J.R., Kolesnikov A., Hendrix J., Young W.B., Shrader W.D., Vijaykumar D., Stephens R., Liu L., Pan L., Mordenti J., Green M.J., and Sukbuntherng J. Bioorg. Med. Chem. Lett. 16 (2006) 2224
30. pKa values calculated using the ACD/Physchem Batch 5.0 Program.
31. South, M. S.; Parlow, J. J.; Jones, D. E.; Case, B.; Dice, T.; Lindmark, R.; Hayes, M. J.; Rueppel, M. L.; Fenton, R.; Franklin, G. W.; Huang, H.; Huang, W.; Kusturin, C.; Long, S. A.; Neumann, W. L.; Reitz, D.; Trujillo, J. I.; Wang, C.; Wood, R.; Zeng, Q.; Mahoney, M. W. WO 2001087854 A1, 2001
32. South, M. S.; Parlow, J. J.; Jones, D. E.; Case, B.; Dice, T.; Lindmark, R.; Hayes, M. J.; Rueppel, M. L.; Fenton, R.; Franklin, G. W.; Huang, H.; Huang, W.; Kusturin, C.; Long, S. A.; Neumann, W. L.; Reitz, D. B.; Trujillo, J. I.; Wang, C.; Wood, R.; Zeng, Q. WO 2000069834 A1, 2001.
33. Boere R.T., Oakley R.T., and Reed R.W. J. Organomet. Chem. 331 (1987) 161
34. Bondinell, W. E.; Callahan, J. F.; Huffman, W. F.; Keenan, R. M.; Ku, T. W. F.; Newlander, K. A. WO 9300095A2, 1993.
35. South, M. S.; Webber, R. K.; Huang, H. C.; Toth, M. V.; Moorman, A. E.; Snyder, J. S.; Scholten, J. A.; Garland, D. J.; Rueppel, M. L.; Neumann, W. L.; Long, S.; Huang, W.; Trujillo, J.; Parlow, J. J.; Jones, D. E.; Case, B.; Hayes, M. J.; Zeng, Q. WO 2003028729 A2, 2003.
36. Peterlin-Masic L., Cesar J., and Zega A. Curr. Pharm. Des. 12 (2006) 73