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This work is licensed under a Creative Commons Attribution 4.0 International License.
Design and Synthesis of Novel Dasatinib Analogues
Corresponding Author(s) : G. Buchappa
Asian Journal of Chemistry,
Vol. 28 No. 6 (2016): Vol 28 Issue 6
Abstract
Design, synthesis, characterization and in vitro biological assay of a series of novel carboxylic acid and amino acid analogs of dasatinib (1) as anticancer agents are reported. Some of the synthesized analogs were identified as potent Src/Abl kinase inhibitors with greater antiproliferative activity against K652 and T315I cancer cell lines. The synthetic process involves condensation of N-(2-chloro-6-methylphenyl)-2-[[6-[4(-1-pipearazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide with carboxylic acids in the presence of dicyclohexylcarbodiimide and oxyma in organic solvent medium. Compounds were characterized and tested for anticancer activity on leukemia cancer cell lines K562 and Baf3/T315. Analogues of lactic acid, mandalic acid, leucine and proline have shown promising antiproliferative activity compared to dasatinib.
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- FDA, FDA Approves Additional Medical Indication for Sprycel; www.fda.gov. FDA; Retrieved 22 March 2013.
- S.G. Buchanan, Targets, 2, 101 (2003); doi:10.1016/S1477-3627(03)02320-1.
- M. Schnürch, B. Waldner, K. Hilber and M.D. Mihovilovic, Bioorg. Med. Chem. Lett., 21, 2149 (2011); doi:10.1016/j.bmcl.2011.01.123.
- N. Vukovic, S. Sukdolak, S. Solujic and T. Milosevic, Arch. Pharm., 341, 491 (2008); doi:10.1002/ardp.200700215.
- A. De Logu, M. Saddi, M.C. Cardia, R. Borgna, C. Sanna, B. Saddi and E. Maccioni, J. Antimicrob. Chemother., 55, 692 (2005); doi:10.1093/jac/dki084.
- Q. Al-Balas, N.G. Anthony, B. Al-Jaidi, A. Alnimr, G. Abbott, A.K. Brown, R.C. Taylor, G.S. Besra, T.D. McHugh, S.H. Gillespie, B.F. Johnston and S.P. Mackay, PLoS One, 4, e5617 (2009); doi:10.1371/journal.pone.0005617.
- T.K. Venkatachalam, E.A. Sudbeck, C. Mao and F.M. Uckun, Bioorg. Med. Chem. Lett., 11, 523 (2001); doi:10.1016/S0960-894X(01)00011-7.
- B.S. Holla, K.V. Malini, B.S. Rao, B.K. Sarojini and N.S. Kumari, Eur. J. Med. Chem., 38, 313 (2003); doi:10.1016/S0223-5234(02)01447-2.
- I.S. Adagu, J. Antimicrob. Chemother., 49, 103 (2002); doi:10.1093/jac/49.1.103.
- W.C. Patt, H.W. Hamilton, M.D. Taylor, M.J. Ryan, D.G. Taylor, C.J.C. Connolly, A.M. Doherty, S.R. Klutchko and I. Sircar, J. Med. Chem., 35, 2562 (1992); doi:10.1021/jm00092a006.
- J.C. Jaen, L.D. Wise, B.W. Caprathe, H. Tecle, S. Bergmeier, C.C. Humblet, T.G. Heffner, L.T. Meltzer and T.A. Pugsley, J. Med. Chem., 33, 311 (1990); doi:10.1021/jm00163a051.
- B.A. Fink, Mortensen, S.R. Stauffer, Z.D. Aron and J.A. Katzenellenbogen, Chem. Biol., 6, 205 (1999); doi:10.1016/S1074-5521(99)80037-4.
- J.E. Van Muijlwijk-Koezen, H. Timmerman, R.C. Vollinga, J. Frijtag von Drabbe Künzel, M. de Groote, S. Visser and A.P. IJzerman, J. Med. Chem., 44, 749 (2001); doi:10.1021/jm0003945.
- J.V. Metzger, Comprehensive Heterocyclic Chemistry I, Pergamon: New York, Vol. 6, 328 (1984).
- B.-C. Chen, R. Droghini, J. Lajeunesse, J. DiMarco, M. Galella and R. Chidambaram, Process for Preparing 2-Aminothiazole-5-Aromatic Carboxamides as Kinase Inhibitors, US Patent 20060004067 A1 (2006).
- D.B. Kitchen, H. Decornez, J.R. Furr and J. Bajorath, J. Nat. Rev. Drug Discov., 3, 935 (2004); doi:10.1038/nrd1549.
- J. Das, R. Padmanabha, P. Chen, D.J. Norris, A.M.P. Doweyko, J.C. Barrish and J. Wityak, Cyclic Protein Tyrosine Kinase Inhibitors, US Patent 6,979,694 B2 (2005).
References
FDA, FDA Approves Additional Medical Indication for Sprycel; www.fda.gov. FDA; Retrieved 22 March 2013.
S.G. Buchanan, Targets, 2, 101 (2003); doi:10.1016/S1477-3627(03)02320-1.
M. Schnürch, B. Waldner, K. Hilber and M.D. Mihovilovic, Bioorg. Med. Chem. Lett., 21, 2149 (2011); doi:10.1016/j.bmcl.2011.01.123.
N. Vukovic, S. Sukdolak, S. Solujic and T. Milosevic, Arch. Pharm., 341, 491 (2008); doi:10.1002/ardp.200700215.
A. De Logu, M. Saddi, M.C. Cardia, R. Borgna, C. Sanna, B. Saddi and E. Maccioni, J. Antimicrob. Chemother., 55, 692 (2005); doi:10.1093/jac/dki084.
Q. Al-Balas, N.G. Anthony, B. Al-Jaidi, A. Alnimr, G. Abbott, A.K. Brown, R.C. Taylor, G.S. Besra, T.D. McHugh, S.H. Gillespie, B.F. Johnston and S.P. Mackay, PLoS One, 4, e5617 (2009); doi:10.1371/journal.pone.0005617.
T.K. Venkatachalam, E.A. Sudbeck, C. Mao and F.M. Uckun, Bioorg. Med. Chem. Lett., 11, 523 (2001); doi:10.1016/S0960-894X(01)00011-7.
B.S. Holla, K.V. Malini, B.S. Rao, B.K. Sarojini and N.S. Kumari, Eur. J. Med. Chem., 38, 313 (2003); doi:10.1016/S0223-5234(02)01447-2.
I.S. Adagu, J. Antimicrob. Chemother., 49, 103 (2002); doi:10.1093/jac/49.1.103.
W.C. Patt, H.W. Hamilton, M.D. Taylor, M.J. Ryan, D.G. Taylor, C.J.C. Connolly, A.M. Doherty, S.R. Klutchko and I. Sircar, J. Med. Chem., 35, 2562 (1992); doi:10.1021/jm00092a006.
J.C. Jaen, L.D. Wise, B.W. Caprathe, H. Tecle, S. Bergmeier, C.C. Humblet, T.G. Heffner, L.T. Meltzer and T.A. Pugsley, J. Med. Chem., 33, 311 (1990); doi:10.1021/jm00163a051.
B.A. Fink, Mortensen, S.R. Stauffer, Z.D. Aron and J.A. Katzenellenbogen, Chem. Biol., 6, 205 (1999); doi:10.1016/S1074-5521(99)80037-4.
J.E. Van Muijlwijk-Koezen, H. Timmerman, R.C. Vollinga, J. Frijtag von Drabbe Künzel, M. de Groote, S. Visser and A.P. IJzerman, J. Med. Chem., 44, 749 (2001); doi:10.1021/jm0003945.
J.V. Metzger, Comprehensive Heterocyclic Chemistry I, Pergamon: New York, Vol. 6, 328 (1984).
B.-C. Chen, R. Droghini, J. Lajeunesse, J. DiMarco, M. Galella and R. Chidambaram, Process for Preparing 2-Aminothiazole-5-Aromatic Carboxamides as Kinase Inhibitors, US Patent 20060004067 A1 (2006).
D.B. Kitchen, H. Decornez, J.R. Furr and J. Bajorath, J. Nat. Rev. Drug Discov., 3, 935 (2004); doi:10.1038/nrd1549.
J. Das, R. Padmanabha, P. Chen, D.J. Norris, A.M.P. Doweyko, J.C. Barrish and J. Wityak, Cyclic Protein Tyrosine Kinase Inhibitors, US Patent 6,979,694 B2 (2005).