Design, synthesis and biological evaluation of novel (E)-α- benzylsulfonyl chalcone derivatives as potential BRAF inhibitors

European Journal of Medicinal Chemistry

Volumn 50, Issue , 2012, Pages 288-295

  Li, Qing Shan ^a   Li, Cui Yun ^a   Lu, Xiang ^a   Zhang, Hui ^a   Zhu, Hai Liang ^a  

^a NANJING UNIVERSITY   (China)

Author keywords

BRAF; Inhibitors; Melanoma; Mutant; Virtual screening

Indexed keywords

2 (4 BROMOBENZYLSULFONYL) 1 PHENYL 3 [4 (TRIFLUOROMETHYL)PHENYL]PROP 2 EN 1 ONE; 2 (4 BROMOBENZYLSULFONYL) 3 (2 CHLOROPHENYL) 1 PHENYLPROP 2 EN 1 ONE; 2 (4 BROMOBENZYLSULFONYL) 3 (4 BROMOPHENYL) 1 PHENYLPROP 2 EN 1 ONE; 2 (4 BROMOBENZYLSULFONYL) 3 (4 FLUOROPHENYL)PHENYLPROP 2 EN 1 ONE; 2 (4 BROMOBENZYLSULFONYL) 3 (4 NITROPHENYL) 1 PHENYLPROP 2 EN 1 ONE; 2 (4 CHLOROBENZYLSULFONYL) 1 PHENYL 3 [4 (TRIFLUOROMETHYL)PHENYL]PROP 2 EN 1 ONE; 2 (4 CHLOROBENZYLSULFONYL) 3 (2 NITROPHENYL) 1 PHENYL PROP 2 EN 1 ONE; 2 (4 CHLOROBENZYLSULFONYL) 3 (4 CHLOROPHENYL) 1 PHENYLPROP 2 EN 1 ONE; 2 (4 CHLOROBENZYLSULFONYL) 3 (4 NITROPHENYL) 1 PHENYL PROP 2 EN 1 ONE; 2 (4 METHOXYBENZYLSULFONYL) 1 PHENYL 3 [4 (TRIFLUOROMETHYL)PHENYL]PROP 2 EN 1 ONE; 2 (4 METHOXYBENZYLSULFONYL) 3 (2 NITROPHENYL) 1 PHENYLPROP 2 EN 1 ONE; 2 (4 METHOXYBENZYLSULFONYL) 3 (4 NITROPHENYL) 1 PHENYLPROP 2 EN 1 ONE; 2 (BENZYLSULFONYL) 1 PHENYL 3 [4 (TRIFLUOROMETHYL) PHENYL] PROP 2 EN 1 ONE; 2 (BENZYLSULFONYL) 3 (2 CHLOROPHENYL ) 1 PHENYLPROP 2 EN 1 ONE; 2 (BENZYLSULFONYL) 3 (2 NITROPHENYL ) 1 PHENYLPROP 2 EN 1 ONE; 2 (BENZYLSULFONYL) 3 (4 BROMOPHENYL) 1 PHENYLPROP 2 EN 1 ONE; 2 (BENZYLSULFONYL) 3 (4 CHLOROPHENYL) 1 PHENYLPROP 2 EN 1 ONE; 2 (BENZYLSULFONYL) 3 (4 FLUOROPHENYL) 1 PHENYLPROP 2 EN 1 ONE; 2 (BENZYLSULFONYL) 3 (4 NITROPHENYL) 1 PHENYLPROP 2 EN 1 ONE; 2 (BROMOBENZYLSULFONYL) 3 (2 NITROPHENYL ) 1 PHENYLPROP 2 EN 1 ONE; 2 (BROMOBENZYLSULFONYL) 3 (4 NITROPHENYL ) 1 PHENYLPROP 2 EN 1 ONE; 3 (2 CHLOROPHENYL) 2 (4 METHOXYBENZYLSULFONYL) 1 PHENYLPROP 2 EN 1 ONE; 3 (4 BROMOPHENYL) 2 (4 CHLOROBENZYLSULFONYL) 1 PHENYL PROP 2 EN 1 ONE; 3 (4 BROMOPHENYL) 2 (4 METHOXYBENZYLSULFONYL) 1 PHENYLPROP 2 EN 1 ONE; 3 (4 CHLOROPHENYL) 2 (4 METHOXYBENZYLSULFONYL) 1 PHENYLPROP 2 EN 1 ONE; 3 (4 FLUOROPHENYL) 2 (4 METHOXYBENZYLSULFONYL) 1 PHENYLPROP 2 EN 1 ONE; ANTINEOPLASTIC AGENT; CHALCONE DERIVATIVE; SORAFENIB; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CELL PROLIFERATION; CONTROLLED STUDY; DRUG DESIGN; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; MELANOMA CELL; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION;

CELL LINE, TUMOR; CELL PROLIFERATION; CHALCONE; CHALCONES; DRUG DESIGN; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; INHIBITORY CONCENTRATION 50; MELANOMA; MOLECULAR STRUCTURE; MUTATION; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONES;

EID: 84862820174     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2012.02.007     Document Type: Article

References (28)

1. M.J. Robinson, and M.H. Cobb Mitogen-activated protein kinase pathways Current Opinion in Cell Biology 9 1997 180 186
2. J.M. Kyriakis, and J. Avruch Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation Physiological Reviews 81 2001 807 869
3. G.L. Johnson, and R. Lapadat Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases Science 298 2002 1911 1912
4. G. Pearson, F. Robinson, T.B. Gibson, B.E. Xu, M. Karandikar, K. Berman, and M.H. Cobb Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions Endocrine Reviews 22 2001 153 183
5. P. Cohen Protein kinases - the major drug targets of the twenty-first century? Nature Reviews Drug Discovery 1 2002 309 315
6. C. Wellbrock, M. Karasarides, and R. Marais The RAF proteins take centre stage Nature Reviews Molecular Cell Biology 5 2004 875 885
7. S.S. Sridhar, D. Hedley, and L.L. Siu Raf kinase as a target for anticancer therapeutics Molecular Cancer Therapeutics 4 2005 677 685
8. J. Avruch, A. Khokhlatchev, J.M. Kyriakis, Z.J. Luo, G. Tzivion, D. Vavvas, and X.F. Zhang Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade Recent Progress in Hormone Research 56 2001 127 155
9. H. Davies, G.R. Bignell, C. Cox, P. Stephens, S. Edkins, S. Clegg, J. Teague, H. Woffendin, M.J. Garnett, W. Bottomley, N. Davis, N. Dicks, R. Ewing, Y. Floyd, K. Gray, S. Hall, R. Hawes, J. Hughes, V. Kosmidou, A. Menzies, 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. Siegler, T.L. Darrow, H. Paterson, R. Marais, C.J. Marshall, R. Wooster, M.R. Stratton, and P.A. Futreal Mutations of the BRAF gene in human cancer Nature 417 2002 949 954
10. J.H. Lee, E.S. Lee, and Y.S. Kim Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid - a meta-analysis Cancer 110 2007 38 46
11. M.J. Garnett, and R. Marais Guilty as charged: B-RAF is a human oncogene Cancer Cell 6 2004 313 319
12. P.T.C. Wan, M.J. Garnett, S.M. Roe, S. Lee, D. Niculescu-Duvaz, V.M. Good, C.M. Jones, C.J. Marshall, C.J. Springer, D. Barford, R. Marais, and P. Cancer Genome Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF Cell 116 2004 855 867
13. C. Wellbrock, L. Ogilvie, D. Hedley, M. Karasarides, J. Martin, D. Niculescu-Duvaz, C.J. Springer, and R. Marais B-V599E-RAF is an oncogene in melanocytes Cancer Research 64 2004 2338 2342
14. J.S. Sebolt-Leopold, and R. Herrera Targeting the mitogen-activated protein kinase cascade to treat cancer Nature Reviews Cancer 4 2004 937 947
15. V. Gray-Schopfer, C. Wellbrock, and R. Marais Melanoma biology and new targeted therapy Nature 445 2007 851 857
16. M. Karasarides, A. Chiloeches, R. Hayward, D. Niculescu-Duvaz, I. Scanlon, F. Friedlos, L. Ogilvie, D. Hedley, J. Martin, C.J. Marshall, C.J. Springer, and R. Marais B-RAF is a therapeutic target in melanoma Oncogene 23 2004 6292 6298
17. B.B. Friday, and A.A. Adjei Advances in targeting the Ras/Raf/MEK/Erk mitogen-activated protein kinase cascade with MEK inhibitors for cancer therapy Clinical Cancer Research 14 2008 342 346
18. A.E. Gould, R. Adams, S. Adhikari, K. Aertgeerts, R. Afroze, C. Blackburn, E.F. Calderwood, R. Chau, J. Chouitar, M.O. Duffey, D.B. England, C. Farrer, N. Forsyth, K. Garcia, J. Gaulin, P.D. Greenspan, R.B. Guo, S.J. Harrison, S.C. Huan, N. Iartchouk, D. Janowick, M.S. Kim, B. Kulkarni, S.P. Langston, J.X. Liu, L.T. Ma, S. Menon, H. Mizutani, E. Paske, C.C. Renou, M. Rezaei, R.S. Rowland, M.D. Sintchak, M.D. Smith, S.G. Stroud, M. Tregay, Y.A. Tian, O.P. Veiby, T.J. Vos, S. Vyskocil, J. Williams, T.L. Xu, J.J. Yang, J. Yano, H.B. Zeng, D.M. Zhang, Q. Zhang, and K.M. Galvin Design and optimization of potent and orally bioavailable Tetrahydronaphthalene Raf inhibitors Journal of Medicinal Chemistry 54 2011 1836 1846
19. G. Bollag, P. Hirth, J. Tsai, J.Z. Zhang, P.N. Ibrahim, H.N. Cho, W. Spevak, C. Zhang, Y. Zhang, G. Habets, E. Burton, B. Wong, G. Tsang, B.L. West, B. Powell, R. Shellooe, A. Marimuthu, H. Nguyen, K.Y.J. Zhang, D.R. Artis, J. Schlessinger, F. Su, B. Higgins, R. Iyer, K. D'Andrea, A. Koehler, M. Stumm, P.S. Lin, R.J. Lee, J. Grippo, I. Puzanov, K.B. Kim, A. Ribas, G.A. McArthur, J.A. Sosman, P.B. Chapman, K.T. Flaherty, X.W. Xu, K.L. Nathanson, and K. Nolop Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma Nature 467 2010 596 599
20. C. Wellbrock, and A. Hurlstone BRAF as therapeutic target in melanoma Biochemical Pharmacology 80 2010 561 567
21. K.S.M. Smalley, M. Xiao, J. Villanueva, T.K. Nguyen, K.T. Flaherty, R. Letrero, P. Van Belle, D.E. Elder, Y. Wang, K.L. Nathanson, and M. Herlyn CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations Oncogene 28 2008 85 94
22. I. Niculescu-Duvaz, E. Roman, S.R. Whittaker, F. Friedlos, R. Kirk, I.J. Scanlon, L.C. Davies, D. Niculescu-Duvaz, R. Marais, and C.J. Springer Novel inhibitors of B-RAF based on a disubstituted pyrazine scaffold. Generation of a nanomolar lead Journal of Medicinal Chemistry 49 2006 407 416
23. 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.F. Wang, F. Karreth, J.C. Lougheed, J. Lee, D. Chau, T.J. Stout, E.W. May, C.M. Rominger, M.D. Schaber, L.S. 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 Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885 Cancer Research 66 2006 11100 11105
24. R. Huey, G.M. Morris, A.J. Olson, and D.S. Goodsell A semiempirical free energy force field with charge-based desolvation Journal of Computational Chemistry 28 2007 1145 1152
25. G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell, and A.J. Olson AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility Journal of Computational Chemistry 30 2009 2785 2791
26. C. Luo, P. Xie, and R. Marmorstein Identification of BRAF inhibitors through in silico screening Journal of Medicinal Chemistry 51 2008 6121 6127
27. M.V.R. Reddy, V.R. Pallela, S.C. Cosenza, M.R. Mallireddigari, R. Patti, M. Bonagura, M. Truongcao, B. Akula, S.S. Jatiani, and E.P. Reddy Design, synthesis and evaluation of (E)-alpha-benzylthio chalcones as novel inhibitors of BCR-ABL kinase Bioorganic & Medicinal Chemistry 18 2010 2317 2326
28. M. Vasudevan, K.K. Gunnam, and M. Parle Antinociceptive and anti-inflammatory effects of Thespesia populnea bark extract Journal of Ethnopharmacology 109 2007 264 270