Synthesis and biological activity of 5-chloro-N4-substituted phenyl-9H-pyrimido[4,5-b]indole-2,4-diamines as vascular endothelial growth factor receptor-2 inhibitors and antiangiogenic agents

Bioorganic and Medicinal Chemistry

Volumn 21, Issue 7, 2013, Pages 1857-1864

  Gangjee, Aleem ^a   Zaware, Nilesh ^a   Raghavan, Sudhir ^a   Disch, Bryan C ^b   Thorpe, Jessica E ^b   Bastian, Anja ^b   Ihnat, Michael A ^b  

^a DUQUESNE UNIVERSITY   (United States)

^b UNIVERSITY OF OKLAHOMA   (United States)

Author keywords

Cytotoxicity; Pyrimido 4,5 b indol synthesis; Receptor tryosine kinase inhibitors; VEGFR 2 inhibitors

Indexed keywords

3 (4 DIMETHYLAMINO BENZYLIDENYL) 2 INDOLINONE; 4 (3 BROMOANILINO) 6,7 DIMETHOXYQUINAZOLINE; 4 [(4' CHLORO 2' FLUORO)PHENYLAMINO] 6,7 DIMETHOXYQUINAZOLINE; 5 CHLORO N4 (3 FLUOROPHENYL) 9H PYRIMIDO[4,5 B]INDOL 2,4 DIAMINE; 5 CHLORO N4 (3 METHOXYPHENYL) 9H PYRIMIDO[4,5 B]INDOL 2,4 DIAMINE; 5 CHLORO N4 (4 CHLORO 2 FLUOROPHENYL) 9H PYRIMIDO[4,5 B]INDOL 2,4 DIAMINE; 5 CHLORO N4 (4 CHLOROPHENYL) 9H PYRIMIDO[4,5 B]INDOL 2,4 DIAMINE; 5 CHLORO N4 (4 ISOPROPYLPHENYL) 9H PYRIMIDO[4,5 B]INDOL 2,4 DIAMINE; 5 CHLORO N4 PHENYL 9H PYRIMIDO[4,5 B]INDOL 2,4 DIAMINE; 5 CHLORO N4 SUBSTITUTED PHENYL 9H PYRIMIDO[4,5 B]INDOLE 2,4 DIAMINE DERIVATIVE; 6,7 DIMETHYL 2 PHENYLQUINOXALINE; ANTINEOPLASTIC AGENT; CB 676475; CISPLATIN; ERLOTINIB; N (4 ANILINO 5 CHLORO 9H PYRIMIDO[4,5 B]INDOL 2 YL) 2,2 DIMETHYLPROPANAMIDE; N (4,5 DICHLORO 9H PYRIMIDO[4,5 B]INDOL 2 YL) 2,2 DIMETHYLPROPANAMIDE; N [5 CHLORO 4 [(3 FLUOROPHENYL)AMINO] 9H PYRIMIDO[4,5 B]INDOL 2 YL] 2,2 DIMETHYLPROPANAMIDE; N [5 CHLORO 4 [(3 METHOXYPHENYL)AMINO] 9H PYRIMIDO[4,5 B]INDOL 2 YL] 2,2 DIMETHYLPROPANAMIDE; N [5 CHLORO 4 [(4 CHLORO 2 FLUOROPHENYL)AMINO] 9H PYRIMIDO[4,5 B]INDOL 2 YL] 2,2 DIMETHYLPROPANAMIDE; N [5 CHLORO 4 [(4 CHLOROPHENYL)AMINO] 9H PYRIMIDO[4,5 B]INDOL 2 YL] 2,2 DIMETHYLPROPANAMIDE; N [5 CHLORO 4 [(4 ISOPROPYLPHENYL)AMINO] 9H PYRIMIDO[4,5 B]INDOL 2 YL] 2,2 DIMETHYLPROPANAMIDE; SEMAXANIB; SUNITINIB; UNCLASSIFIED DRUG; VASCULOTROPIN INHIBITOR;

ANTIANGIOGENIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG POTENCY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; NUCLEOPHILICITY; SIGNAL TRANSDUCTION; SUBSTITUTION REACTION;

ANGIOGENESIS INHIBITORS; CELL LINE, TUMOR; DIAMINES; HALOGENATION; HUMANS; INDOLES; PYRIMIDINES; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 84875229136     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2013.01.040     Document Type: Article

References (40)

1. G. Manning, D.B. Whyte, R. Martinez, T. Hunter, and S. Sudarsanam Science (Washington, DC, US) 298 2002 1912-1916, 1933-1934
2. P. Blume-Jensen, and T. Hunter Nature 411 2001 355 365
3. J. Tabernero Mol. Cancer Res. 5 2007 203 220
4. A. Gschwind, O.M. Fischer, and A. Ullrich Nat. Rev. Cancer 4 2004 361 370
5. A.R. Quesada, R. Munoz-Chapuli, and M.A. Medina Med. Res. Rev. 26 2006 483 530
6. G. Marcucci, D. Perrotti, and M.A. Caligiuri Clin. Cancer Res. 9 2003 1333 1337 Clin. Cancer Res. 2003, 9, 1248-1252
7. A.N. Mohamed, P. Pemberton, J. Zonder, and C.A. Schiffer Clin. Cancer Res. 9 2003 1333 1337
8. C. Gridelli, P. Maione, F. Del Gaizo, G. Colantuoni, C. Guerriero, C. Ferrara, D. Nicolella, D. Comunale, A. De Vita, and A. Rossi Oncologist 12 2007 191 200
9. L.Q.M. Chow, and S.G. Eckhardt J. Clin. Oncol. 25 2007 884 896
10. J. Das, P. Chen, D. Norris, R. Padmanabha, J. Lin, R.V. Moquin, Z. Shen, L.S. Cook, A.M. Doweyko, S. Pitt, S. Pang, D.R. Shen, Q. Fang, H.F. de Fex, K.W. McIntyre, D.J. Shuster, K.M. Gillooly, K. Behnia, G.L. Schieven, J. Wityak, and J.C. Barrish J. Med. Chem. 49 2006 6819 6832
11. M.W. Deininger Clin. Cancer Res. 14 2008 4027 4031
12. S.R.D. Johnston, and A. Leary Drugs Today 42 2006 441 453
13. R. Morphy J. Med. Chem. 53 2010 1413 1437
14. M.W. Karaman, S. Herrgard, D.K. Treiber, P. Gallant, C.E. Atteridge, B.T. Campbell, K.W. Chan, P. Ciceri, M.I. Davis, P.T. Edeen, R. Faraoni, M. Floyd, J.P. Hunt, D.J. Lockhart, Z.V. Milanov, M.J. Morrison, G. Pallares, H.K. Patel, S. Pritchard, L.M. Wodicka, and P.P. Zarrinkar Nat. Biotechnol. 26 2008 127 132
15. P. Bamborough, D. Drewry, G. Harper, G.K. Smith, and K. Schneider J. Med. Chem. 51 2008 7898 7914
16. T. Force, D.S. Krause, and R.A. Van Etten Nat. Rev. Cancer 7 2007 332 344
17. A. Crespo, X. Zhang, and A. Fernandez J. Med. Chem. 51 2008 4890 4898
18. R. Kerkelae, L. Grazette, R. Yacobi, C. Iliescu, R. Patten, C. Beahm, B. Walters, S. Shevtsov, S. Pesant, F.J. Clubb, A. Rosenzweig, R.N. Salomon, R.A. Van Etten, J. Alroy, J.-B. Durand, and T. Force Nat. Med. 12 2006 908 916
19. P.M. Traxler, P. Furet, H. Mett, E. Buchdunger, T. Meyer, and N. Lydon J. Med. Chem. 39 1996 2285 2292
20. H.D.H. Showalter, A.J. Bridges, H. Zhou, A.D. Sercel, A. McMichael, and D.W. Fry J. Med. Chem. 42 1999 5464 5474
21. L. Han, A. Lorincz, and S. Sukumar B. Teicher, L. Ellis, Antiangiogenic Agents in Cancer Therapy Vol. 2 2008 Humana Press New Jersey 331 352
22. N. Ferrara Oncologist 9 2004 2 10
23. N. Ferrara, H.-P. Gerber, and J. LeCouter Nat. Med. 9 2003 669 676
24. S. Shinkaruk, M. Bayle, G. Lain, and G. Deleris Curr. Med. Chem.: Anticancer Agents 3 2003 95 117
25. SYBYL. X 1.3 ed.; Tripos Inc.: St. Louis, MO.
26. Lead IT. 2.1.0 ed.; Biosolve IT GmbH: St. Augustin, Germany.
27. A. Gangjee, J. Yang, M.A. Ihnat, and S. Kamat Bioorg. Med. Chem. 11 2003 5155 5170
28. S.A. Laufer, D.M. Domeyer, T.R.F. Scior, W. Albrecht, and D.R.J. Hauser J. Med. Chem. 48 2005 710 722
29. K. Choowongkomon, O. Sawatdichaikul, N. Songtawee, and J. Limtrakul Molecules 15 2010 4041 4054
30. G. Bold, K.-H. Altmann, J. Frei, M. Lang, P.W. Manley, P. Traxler, B. Wietfeld, J. Brueggen, E. Buchdunger, R. Cozens, S. Ferrari, P. Furet, F. Hofmann, G. Martiny-Baron, J. Mestan, J. Roesel, M. Sills, D. Stover, F. Acemoglu, E. Boss, R. Emmenegger, L. Laesser, E. Masso, R. Roth, C. Schlachter, W. Vetterli, D. Wyss, and J.M. Wood J. Med. Chem. 43 2000 2310 2323
31. P. Traxler, G. Bold, J. Frei, M. Lang, N. Lydon, H. Mett, E. Buchdunger, T. Meyer, M. Mueller, and P. Furet J. Med. Chem. 40 1997 3601 3616
32. L.F. Hennequin, A.P. Thomas, C. Johnstone, E.S. Stokes, P.A. Ple, J.J. Lohmann, D.J. Ogilvie, M. Dukes, S.R. Wedge, J.O. Curwen, and J. Kendrew J. Med. Chem. 42 1999 5369 5389
33. A. Gangjee, N. Zaware, S. Raghavan, M. Ihnat, S. Shenoy, and R.L. Kisliuk J. Med. Chem. 53 2010 1563 1578
34. S.M. Wilson, M.J. Barsoum, B.W. Wilson, and P.A. Pappone Cell Prolif. 32 1999 131 140
35. A. Arora, and E.M. Scholar J. Pharmacol. Exp. Ther. 315 2005 971 979
36. L.F. Hennequin, A.P. Thomas, C. Johnstone, E.S.E. Stokes, P.A. Ple, J.-J.M. Lohmann, D.J. Ogilvie, M. Dukes, S.R. Wedge, J.O. Curwen, J. Kendrew, and C. Lambert-van der Brempt J. Med. Chem. 42 1999 5369 5389
37. M. Kovalenko, A. Gazit, A. Bohmer, C. Rorsman, L. Ronnstrand, C.H. Heldin, J. Waltenberger, F.D. Bohmer, and A. Levitzki Cancer Res. 54 1994 6106-14
38. R.L. Comis Oncologist 10 2005 467 470
39. Y. Miyazaki, S. Matsunaga, J. Tang, Y. Maeda, M. Nakano, R.J. Philippe, M. Shibahara, W. Liu, H. Sato, L. Wang, and R.T. Nolte Bioorg. Med. Chem. Lett. 15 2005 2203 2207
40. Molecular Operating Environment (MOE). 10th ed.; C. C. G., Inc.: 1255 University Street, Suite 1600, Montreal, Quebec, Canada, 2010.