Design, synthesis, and evaluation of orally active inhibitors of plasminogen activator inhibitor-1 (PAI-1) production

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 24, 2008, Pages 6419-6422

  Miyazaki, Hiroshi ^a   Ogiku, Tsuyoshi ^a   Sai, Hiroshi ^a   Ohmizu, Hiroshi ^a   Murakami, Jun ^a   Ohtani, Akio ^a  

^a MITSUBISHI TANABE PHARMA CORPORATION   (Japan)

Author keywords

Inhibitor of PAI 1 production; Plasminogen activator inhibitor 1 (PAI 1); T 2639

Indexed keywords

1,3 BUTADIENE; 3 BENZYLIDENE 4 (3,4,5 TRIMETHOXYBENZYLIDENE)SUCCINIMIDE; ANTICOAGULANT AGENT; IMIDE; MYOTONIC DYSTROPHY PROTEIN KINASE; PLASMINOGEN ACTIVATOR INHIBITOR 1; T 2639; UNCLASSIFIED DRUG;

ARTICLE; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG POTENCY; DRUG SCREENING; DRUG STABILITY; DRUG SYNTHESIS; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; BENZYLIDENE COMPOUNDS; BIOLOGICAL AVAILABILITY; CHEMISTRY, PHARMACEUTICAL; DOGS; DRUG ADMINISTRATION ROUTES; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HUMANS; MODELS, CHEMICAL; PLASMINOGEN ACTIVATOR INHIBITOR 1; RATS; SOLUBILITY; SUCCINIMIDES;

EID: 56249117664     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.10.067     Document Type: Article

References (27)

1. Schneiderman J., and Loskutoff D.J. Trends Cardiovasc. Med. 1 (1991) 99
2. Nilsson I.M., Ljungner H., and Tengborn L. Br. J. Med. 290 (1985) 1453
3. Wiman B., Ljungberg S., Chmielewska J., Urden G., Blomback M., and Johnsson H. J. Lab. Clin. Med. 105 (1985) 265
4. Juhan-Vague I., Valadier J., Alessi M.C., Aillaud M.F., Ansaldi J., Philip-Joet C., Holvet J., Serradimigni A., and Collen D. Thromb. Haemost. 57 (1987) 67
5. Wieczorek I., Ludlam C.A., and Fox K.A.A. Am. J. Cardiol. 74 (1994) 424
6. Krishnamurti C., Barr C.F., Hassett M.A., Young G.D., and Alving B.M. Blood 69 (1987) 798
7. Reilly C.F., Fujita T., Mayer E.F., and Siefried M.E. Arterioscler. Thromb. 11 (1991) 1276
8. Carmeliet P., Stassen J.M., Schoonjans L., Ream B., Van den Oord J.J., De Mol M., Mulligan R.C., and Collen D. J. Clin. Invest. 92 (1993) 2756
9. Levi M., Biemond B.J., Van Zonnenveld A.J., Ten Cate J.W., and Pannekoek H. Circulation 85 (1992) 305
10. Biemond B.J., Levi M., Coronel R., Janse M.J., Ten Cate J.W., and Pannekoek H. Circulation 1 (1995) 1175
11. Folkes A., Roe M.B., Sohal S., Golec J., Faint R., Brooks T., and Charlton P. Bioorg. Med. Chem. Lett. 11 (2001) 2589
12. Folkes A., Brown S.D., Canne L.E., Chan J., Engelhardt E., Epshteyn S., Faint R., Golec J., Hanel A., Kearney E., Leahy J.W., Mac M., Matthews D., Prisbylla M.P., Sanderson J., Simon R.J., Tesfai Z., Vicker N., Wang S., Webb R.R., and Charlton P. Bioorg. Med. Chem. Lett. 12 (2002) 1063
13. Wang S., Golec J., Miller W., Milutinovic S., Folkes A., Williams S., Brooks T., Hardman K., Charlton P., Wren S., and Spencer J. Bioorg. Med. Chem. Lett. 12 (2002) 2367
14. De Nanteuil G., Lila-Ambroise C., Rupin A., Vallez M.O., and Verbeuren T.J. Bioorg. Med. Chem. Lett. 13 (2003) 1705
15. Ye B., Bauer S., Buckman B.O., Ghannam A., Griedel B.D., Khim S.K., Lee W., Sacchi K.L., Shaw K.J., Liang A., Wu Q., and Zhao Z. Bioorg. Med. Chem. Lett. 13 (2003) 3361
16. Ye B., Chou Y.L., Karanjawala R., Lee W., Lu S.F., Shaw K.J., Jones S., Lentz D., Liang A., Tseng J.L., Wu Q., and Zhao Z. Bioorg. Med. Chem. Lett. 14 (2004) 761
17. Gopalsamy A., Kincaid S.L., Ellingboe J.W., Groeling T.M., Antrilli T.M., Krishnamurthy G., Aulabaugh A., Friedrichs G.S., and Crandall D.L. Bioorg. Med. Chem. Lett. 14 (2004) 3477
18. Hu B., Jetter J.W., Wrobel J.E., Antrilli T.M., Bauer J.S., Di L., Polakowski S., Jain U., and Crandall D.L. Bioorg. Med. Chem. Lett. 15 (2005) 3514
19. Elokdah H., Abou-Gharbia M., Hennan J.K., McFarlane G., Mugford C.P., Krishnamurthy G., and Crandall D.L. J. Med. Chem. 47 (2004) 3491
20. Ohtani A., Takagi T., Hirano A., Murakami J., and Sasaki Y. J. Biochem. 120 (1996) 1203
21. Ohtani A., and Murakami J. Fibrinolysis Proteol. 11 (1997) 45
22. Ohtani A., Murakami J., and Hirano-Wakimoto A. Eur. J. Pharmacol. 330 (1997) 151
23. Sai H., Ogiku T., Ohmizu H., and Ohtani A. Chem. Pharm. Bull. 54 (2006) 1686
24. Johnson W.S., and Daube G.H. Org. React. 6 (1951) 1
25. -3, Z = 4, R = 0.046, Rw = 0.165, CCDC Reference No. 705024.
26. We saw during another project that the 4-methoxy group was predominantly demethylated to phenol metabolite in the 3,4,5-trimethoxyphenyl group (unpublished result).
27. Compounds (3 mg/kg per day) were orally administered for three consecutive days. Two hours after the last administration, thrombi were induced and their dry weights were measured. See Ref. 11.