TIE-2/VEGF-R2 SAR and in vitro activity of C3-acyl dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole analogs

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 7, 2008, Pages 2368-2372

  Underiner, Ted L ^a   Ruggeri, Bruce ^a   Aimone, Lisa ^a   Albom, Mark ^a   Angeles, Thelma ^a   Chang, Hong ^a   Hudkins, Robert L ^a   Hunter, Kathryn ^a   Josef, Kurt ^a   Robinson, Candy ^a   Weinberg, Linda ^a   Yang, Shi ^a   Zulli, Allison ^a  

^a CEPHALON INC   (United States)

Author keywords

Anti angiogenic; Kinase inhibitor; TIE 2; VEGF R2; VEGFR2

Indexed keywords

ANGIOPOIETIN RECEPTOR; ANGIOTENSIN I; CARBAZOLE DERIVATIVE; CARBONYL DERIVATIVE; RECEPTOR BLOCKING AGENT; VASCULOTROPIN RECEPTOR 2;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIANGIOGENIC ACTIVITY; AORTA; AREA UNDER THE CURVE; ARTICLE; CELL ASSAY; CELL STIMULATION; CHEMICAL ANALYSIS; CHEMOTAXIS; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG RECEPTOR BINDING; ENZYME ASSAY; HUMAN; HUMAN CELL; IN VITRO STUDY; MICROVASCULATURE; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; TISSUE CULTURE;

ACYLATION; ANGIOGENESIS INHIBITORS; ANGIOTENSIN I; ANIMALS; AORTA; BIOLOGICAL AVAILABILITY; CELLS, CULTURED; CHEMOTAXIS; ENDOTHELIAL CELLS; ENZYME INHIBITORS; INDAZOLES; INDOLES; MODELS, CHEMICAL; RATS; RECEPTOR, TIE-2; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES; UMBILICAL VEINS; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

RATTUS;

EID: 41149130389     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.02.069     Document Type: Article

References (34)

1. Carmeliet P., and Jain R.K. Nature 407 (2000) 249
2. Hanahan D. Science 277 (1997) 48
3. Griffioen A.W., and Molema G. Pharmacol. Rev. 52 (2000) 237
4. Folkman, J. In Cancer Medicine, 5th ed.; Holland, J. E., Frei, I. E., Bast, J., Kufe, D., Pollock, R., Weichselbaum, R., Eds.; Dekker, Inc.: Ontario, 2000; pp 132-152.
5. Korpelainen E.I., and Alitalo K. Curr. Opin. Cell Biol. 10 (1998) 159
6. Ferrara N., and Davis-Smyth T. Endocrine Rev. 18 (1997) 4
7. Neufeld G., Cohen T., Gengrinovitch S., and Poltorak Z. FASEB J. 13 (1999) 9
8. Gale N.W., and Yancopoulos G.D. Gene Dev. 13 (1999) 1055
9. Jones N., Iljin K., Dumont D.J., and Alitalo K. Nat. Rev. Mol. Cell Biol. 2 (2001) 257
10. Giordano, F.J.;.
11. Johnson R.S. Curr. Opin. Gen. Dev. 11 (2001) 35
12. Cristofanilli M., Charnsangavej C., and Hortobagyi G.N. Nat. Rev. Drug Disc. 1 (2002) 415
13. Uemura A., Ogawa M., Hirashima M., Fujiwara T., Koyama S., Takagi H., Honda Y., Wiegand S.J., Yancopoulos G.D., and Nishikawa S.-I. J. Clin. Invest. 110 (2002) 1619
14. Visconti R.P., Richardson C.D., and Sato T.N. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 8219
15. Tsigkos S., Koutsilieris M., and Papapetropoulos A. Expert Opin. Invest. Drugs 12 (2003) 933
16. Asahara T., Chen D., Takahashi T., Fujikawa K., Kearney M., Magner M., Yancopoulos G.D., and Isner J.M. Circ. Res. 83 (1998) 233
17. Lobov I.B., Brooks P.C., and Lang R.A. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 11205
18. Beebe J.S., Jani J.P., Knauth E., Goodwin P., Higdon C., Rossi A.M., Emerson E., Finkelstein M., Floyd E., Harriman S., Atherton J., Hillerman S., Soderstrom C., Kou K., Gant T., Noe M.C., Foster B., Rastinejad F., Marx M.A., Schaeffer T., Whalen P.M., and Roberts W.G. Cancer Res. 63 (2003) 7301
19. Hasegawa M., Nishigaki N., Washio Y., Kano K., Harris P.A., Sato H., Mori I., West R.I., Shibahara M., Toyoda H., Wang L., Nolte R.T., Veal J.M., and Cheung M. J. Med. Chem. 50 (2007) 4453
20. Ji Z., Ahmed A.A., Albert D.H., Bouska J.J., Bousquet P.F., Cunha G.A., Glaser K.B., Guo J., Li J., Marcotte P.A., Moskey M.D., Pease L.J., Stewart K.D., Yates M., Davidsen S.K., and Michaelides M.R. Bioorg. Med. Chem. Lett. 16 (2006) 4326
21. Miyazaki Y., Tang J., Maeda Y., Nakano M., Wang L., Nolte R.T., Sato H., Sugai M., Okamoto Y., Truesdale A.T., Hassler D.F., Nartey E.N., Patrick D.R., Ho M.L., and Ozawa K. Bioorg. Med. Chem. Lett. 17 (2007) 1773
22. Miyazakia Y., Matsunagaa S., Tanga J., Maedaa Y., Nakanoa M., Philippea R.J., Shibaharaa M., Liub W., Satoa H., Wangb L., and Nolteb R.T. Bioorg. Med. Chem. Lett. 15 (2005) 2203
23. Stieber F., Mazitschek R., Soric N., Giannis A., and Waldmann H. Angew. Chem., Int. Ed. 41 (2002) 4757
24. Becknell N.C., Zulli A.L., Angeles T.S., Yang S., Albom M.S., Aimone L.D., Robinson C., Chang H., and Hudkins R.L. Bioorg. Med. Chem. Lett. 16 (2006) 5368
25. Gingrich D.E., Reddy D.R., Iqbal M.A., Singh J., Aimone L.D., Angeles T.S., Albom M., Yang S., Meyer S., Ator M., Robinson C., Ruggeri B.A., Dionne C.A., Vaught J.L., Mallamo J.P., and Hudkins R.L. J. Med. Chem. 46 (2003) 5375-5388
26. Ruggeri B., Singh J., Gingrich D., Angeles T., Albom M., Chang H., Robinson C., Hunter K., Dobrzanski P., Jones-Bolin S., Aimone L., Klein-Szanto A., Herbert J.-M., Bono F., Schaeffer P., Casellas P., Bourie B., Pili R., Isaacs J., Ator M., Hudkins R., Vaught J., Mallamo J., and Dionne C. Cancer Res. 63 (2003) 5978
27. Hudkins, R. L.; Zulli, A. L.; Reddy, D. R.; Gingrich, D. E.; Tao, M.; Becknell, N. C.; Diebold, J. L.; Underiner, T. L. U.S. Patent Appl. 2005143442 A1, 2005.
28. Hudkins, R. L.; Zulli, A. L.; Reddy, D. R.; Tao, M.; Underiner, T. L. U.S. Patent Appl. 2005137245 A1, 2005.
29. Cellular activity was assessed with a VEGF-R2 autophosphorylation assay as described in Ref. 9a.
30. A TIE-2/DHI-carbazole co-crystal structure was obtained and will be reported elsewhere. The structure was refined and used for docking studies with 7e.
31. Ruggeri B., Singh J., Gingrich D., Angeles T., Albom M., Chang H., Robinson C., Hunter K., Dobrzanski P., Jones-Bolin S., Aimone L., Klein-Szanto A., Herbert J.-M., Bono F., Schaeffer P., Casellas P., Bourie B., Pili R., Isaacs J., Ator M., Hudkins R., Vaught J., Mallamo J., and Dionne C. Cancer Res. 63 (2003) 5978
32. http://www.millipore.com/drugdiscovery/svp3/profilerxl.
33. Dandu, R.; Zulli, A. L.; Bacon, E.; Underiner, T.; Robinson, C.; Chang, H.; Miknyoczki, S.; Grobelny, J.; Ruggeri, B. A.; Angeles, T. S.; Aimone, L. D.; Hudkins, R. L. Presented at the 234th National Meeting of the American Chemical Society, Boston, MA, August 2007.
34. Dandu R., Zulli A.L., Bacon E.R., Underiner T., Robinson C., Chang H., Miknyoczki S., Grobelny J., Ruggeri B.A., Yang S., Albom M.S., Angeles T.S., Aimone L.D., and Hudkins R.L. Bioorg. Med. Chem. Lett. 18 (2008) 1916