Design, modification and 3D QSAR studies of novel 2,3-dihydrobenzo[b][1,4] dioxin-containing 4,5-dihydro-1H-pyrazole derivatives as inhibitors of B-Raf kinase

Bioorganic and Medicinal Chemistry

Volumn 20, Issue 20, 2012, Pages 6048-6058

  Yang, Yu Shun ^a   Li, Qing Shan ^a   Sun, Shuai ^a   Zhang, Yan Bin ^a   Wang, Xiao Liang ^a   Zhang, Fei ^a   Tang, Jian Feng ^a   Zhu, Hai Liang ^a  

^a NANJING UNIVERSITY   (China)

Author keywords

Antitumor activity; B Raf; Dioxin; Modification; Pyrazole

Indexed keywords

(2,3 DIHYDROBENZO[B][1,4]DIOXIN 2 YL) (3,5 DIPHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL)METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 2 YL) [3 (4 METHOXYPHENYL) 5 PHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 2 YL) [5 (3 FLUOROPHENYL) 3 PHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 2 YL) [5 (4 FLUOROPHENYL) 3 PHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 2 YL) [5 (4 METHOXYPHENYL) 3 PHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL) (3,5 DIPHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL)METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL) [3 (4 METHOXYPHENYL) 5 PHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL) [5 (2 FLUOROPHENYL) 3 (4 METHOXYPHENYL) 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL) [5 (2 FLUOROPHENYL) 3 PHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL) [5 (3 FLUOROPHENYL) 3 (4 METHOXYPHENYL) 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL) [5 (3 FLUOROPHENYL) 3 PHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL) [5 (4 FLUOROPHENYL) 3 (4 METHOXYPHENYL) 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL) [5 (4 FLUOROPHENYL) 3 PHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL) [5 (4 METHOXYPHENYL) 3 PHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL]METHANONE; 2,3 DIHYDROBENZO[B][1,4]DIOXIN; 4,5 DIHYDRO 1H PYRAZOLE DERIVATIVE; [3 (4 BROMOPHENYL) 5 (2 FLUOROPHENYL) 4,5 DIHYDRO 1H PYRAZOL 1 YL] (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL)METHANONE; [3 (4 BROMOPHENYL) 5 (3 FLUOROPHENYL) 4,5 DIHYDRO 1H PYRAZOL 1 YL] (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL)METHANONE; [3 (4 BROMOPHENYL) 5 (4 FLUOROPHENYL) 4,5 DIHYDRO 1H PYRAZOL 1 YL] (2,3 DIHYDROBENZO[B][1,4]DIOXIN 2 YL)METHANONE; [3 (4 BROMOPHENYL) 5 (4 FLUOROPHENYL) 4,5 DIHYDRO 1H PYRAZOL 1 YL] (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL)METHANONE; [3 (4 BROMOPHENYL) 5 (4 METHOXYPHENYL) 4,5 DIHYDRO 1H PYRAZOL 1 YL] (2,3 DIHYDROBENZO[B][1,4]DIOXIN 2 YL)METHANONE; [3 (4 BROMOPHENYL) 5 (4 METHOXYPHENYL) 4,5 DIHYDRO 1H PYRAZOL 1 YL] (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL)METHANONE; [3 (4 BROMOPHENYL) 5 PHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL] (2,3 DIHYDROBENZO[B][1,4]DIOXIN 2 YL)METHANONE; [3 (4 BROMOPHENYL) 5 PHENYL 4,5 DIHYDRO 1H PYRAZOL 1 YL] (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL)METHANONE; [3,5 BIS(4 METHOXYPHENYL) 4,5 DIHYDRO 1H PYRAZOL 1 YL] (2,3 DIHYDROBENZO[B][1,4]DIOXIN 2 YL)METHANONE; [3,5 BIS(4 METHOXYPHENYL) 4,5 DIHYDRO 1H PYRAZOL 1 YL] (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL)METHANONE; B RAF KINASE; B RAF KINASE INHIBITOR; ERLOTINIB; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACUTE ORAL TOXICITY; ACUTE TOXICITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; CHEMICAL MODIFICATION; CONTROLLED STUDY; CRYSTALLIZATION; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; HUMAN; HUMAN CELL; IC 50; LD 50; MOLECULAR DOCKING; MOLECULAR DYNAMICS; PROTEIN PHOSPHORYLATION; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

BINDING SITES; CELL LINE, TUMOR; CELL PROLIFERATION; DIOXANES; DIOXINS; DRUG DESIGN; HUMANS; MOLECULAR DOCKING SIMULATION; PROTEIN KINASE INHIBITORS; PROTEIN STRUCTURE, TERTIARY; PROTO-ONCOGENE PROTEINS B-RAF; PYRAZOLES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; QUINAZOLINES; THERMODYNAMICS;

EID: 84866916846     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2012.08.043     Document Type: Article

References (25)

1. A.S. El-Aza, M.A. Al-Omar, A.M. Abdel-Aziz, N.I. Abdel-Aziz, A.A. El-Sayed, A.M. Aleisa, M.M. Sayed-Ahmed, and S.G. Abdel-Hamide Eur. J. Med. Chem. 45 2010 4188
2. R. Hoshino, Y. Chantani, T. Yamori, T. Tsuruo, H. Oka, O. Yoshida, Y. Shimada, S. Ari-I, H. Wada, J. Fujimoto, and M. Kohno Oncogene 18 1999 813
3. N. Li, D. Batt, and M. Warmuth Curr. Opin. Investig. Drugs 8 2007 452
4. H. Davies, G.R. Bignell, C. Cox, P. Stephens, S. Edkins, S. Clegg, J. Teague, H. Woffendin, M.J. Garnett, W. Bottomley, N. Davis, E. Dicks, R. Ewing, Y. Floyd, K. Gray, S. Hall, R. Hawes, J. Hughes, V. Kosmidou, A. Menzles, C. Mould, A. Parker, C. Stevens, S. Watt, S. Hooper, R. Wilson, H. Jayatilake, B.A. Gusterson, C. Cooper, J. Shipley, D. Hargrave, K. Pritchard-Jones, N. Maitland, G. Chenevix-Trench, G.J. Riggins, D.D. Bigner, G. Palmieri, A. Cossu, A. Flanagan, A. Nicholson, J.W.C. Ho, S.Y. Leung, S.T. Yuen, B.L. Weber, H.F. Seigler, T.L. Darrow, H. Paterson, R. Marais, C.J. Marshall, R. Wooster, M.R. Stratton, and P.A. Futreal Nature 417 2002 949
5. Y. Cohen, M. Xing, E. Mambo, Z. Guo, G. Wu, B. Trink, U. Beller, W.H. Westra, P.W. Landenson, and D. Sidransky J. Natl. Cancer Inst. 95 2003 625
6. X. Xu, R.M. Quiros, P. Gattuso, K.B. Ain, and R.A. Prinz Cancer Res. 63 2003 4561
7. K. Kalinsky, and F.G. Haluska Expert Rev. Anticancer Ther. 7 2007 715
8. D.S. Dhillon, S. Hagan, O. Rath, and W. Kolch Oncogene 26 2007 3279
9. P.T. Wan, M.J. Garnet, S.M. Roe, S. Lee, D. Niculescu-Duvaz, V.M. Good, C.M. Jones, C.J. Marshall, C.J. Springer, D. Barford, and R. Marais Cell 116 2004 855
10. S.M. Wilhelm, C. Carter, L.Y. Tang, D. Wilkie, A. McNabola, H. Rong, C. Chen, X.M. Zhang, P. Vincent, M. McHugh, Y.C. Cao, J. Shujath, S. Gawlak, D. Eveleigh, B. Rowley, L. Liu, L. Adnane, M. Lynch, D. Auclair, I. Taylor, R. Gedrich, A. Voznesensky, B. Riedl, L.E. Post, G. Bollag, and P.A. Trail Cancer Res. 64 2004 7099
11. P.N. Ibrahim, J. Zhang, H. Cho, S. Mamo, R. Bremer, S. Gillette, A. Kumar, D. Fong, W. Wang, Y.-L. Zhu, A. Marimuthu, Y. Suzuki, B. Lam, J. Rice, J. Tsai, C. Settachatgul, R. Shelloe, J. Cantwell, B. West, B. Powell, G. Habets, C. Zhang, D.R. Artis, P. Hirth, and G. Bollag Abstr. Pap. Am. Chem. Soc. 232 2006
12. U. McDermott, S.V. Sharma, L. Dowell, P. Greninger, C. Montagut, J. Lamb, H. Archibald, R. Raudales, A. Tam, D. Lee, S.M. Rothenberg, J.G. Supko, R. Sordella, L.E. Ulkus, A.J. Iafrate, S. Maheswaran, C.N. Njauw, H. Tsao, L. Drew, J.H. Hanke, X.-J. Ma, M.G. Erlander, N.S. Gray, D.A. Haber, and J. Settleman Proc. Natl. Acad. Sci. U.S.A. 104 2007 19936
13. A.J. King, D.R. Patrick, R.S. Batorsky, M.L. Ho, H.T. Do, S.Y. Zhang, R. Kumar, D.W. Rusnak, A.K. Takle, D.M. Wilson, E. Hugger, L. Wang, F. Karreth, J.C. Lougheed, J. Lee, D. Chau, T.J. Stout, E.W. May, C.M. Rominger, M.D. Schaber, L. Luo, A.S. Lakdawala, J.L. Adams, R.G. Contractor, K.S.M. Smalley, M. Herlyn, M.M. Morrissey, D.A. Tuveson, and P.S. Huang Cancer Res. 66 2006 11100
14. R.G. Ridley, W. Hofheinz, H. Matile, C. Jaquet, A. Dorn, R. Masciadri, S. Jolidon, W.F. Richter, A. Guenzi, M.A. Girometta, H. Urwyler, W. Huber, S. Thaithong, and W. Peters Antimicrob. Agents Chemother. 1996 1846 40
15. D.Y.D. De, F.M. Krogstad, L.D. Byers, and D.J. Krogstad J. Med. Chem. 41 1998 4918
16. D. Azarifar, and H. Ghasemnejad Molecules 8 2003 642
17. C. Blackburn, M.O. Duffy, A.E. Gould, B. Kulkarni, J.X. Liu, S. Menon, M. Nagayoshi, T.J. Vos, and J. Williams Bioorg. Med. Chem. Lett. 20 2010 4795
18. C.Y. Li, Y. Li, Q.S. Li, X.G. Sun, R. Wei, H.B. Gong, and H.L. Zhu Bioorg. Med. Chem. 20 2012 3746
19. M.T. Vazquez, G. Rosell, and M.D. Pujol Farmaco 51 1996 215
20. Y. Harrak, G. Rosell, G. Daidone, S. Plescia, D. Schillaci, and M.D. Pujol Bioorg. Med. Chem. 15 2007 4876
21. M.T. Vasquez, G. Rosell, and M.D. Pujol Eur. J. Med. Chem. 32 1997 529
22. M.Z. Xu, W.S. Lee, J.M. Han, H.W. Oh, D.S. Park, G.R. Tian, T.S. Jeong, and H.Y. Park Bioorg. Med. Chem. 14 2006 7826
23. P. Kirkpatrick Nat. Rev. Drug Disc. 3 2004 299
24. B.J. Newhouse, J.D. Hansen, J. Grina, M. Welch, G. Topalov, N. Littman, M. Callejo, M. Martinson, S. Galbraith, E.R. Laird, B.J. Brandbuber, G. Vigers, T. Morales, R. Woessner, N. Randolph, J. Lyssikatos, and A. Olivero Bioorg. Med. Chem. Lett. 21 2011 3488
25. G.S. Wu, D.H. Robertson, C.L. Brooks, and M. Vieth J. Comput. Chem. 24 2003 1549