Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 5, 2010, Pages 1573-1577

  Lee, Junghun ^a   Kim, Hwan ^a   Yu, Hana ^a   Chung, Jae Yoon ^a   Oh, Chang Hyun ^a   Yoo, Kyung Ho ^a   Sim, Taebo ^a   Hah, Jung Mi ^a  

^a Korea Institute of Science and Technology   (South Korea)

Author keywords

Antiproliferative activity; BRAF; CRAF; Melanoma cell line; Pyrimidin 4 yl 1H imidazol 2 yl derivatives; Selectivity

Indexed keywords

AMIDE; CARBONYL DERIVATIVE; IMIDAZOLE; IMIDAZOLE DERIVATIVE; SORAFENIB; UREA DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CELL PROLIFERATION; CONTROLLED STUDY; DRUG INHIBITION; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HYDROPHOBICITY; IC 50; MELANOMA CELL; STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; BENZENESULFONATES; BINDING SITES; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; DRUG DISCOVERY; HUMANS; IMIDAZOLES; MELANOMA; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; PROTO-ONCOGENE PROTEINS C-RAF; PYRIDINES; PYRIMIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 76649090272     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.01.064     Document Type: Article

References (22)

1. Jemal A., Siegel R., and Ward E. CA Cancer J. Clin. 58 (2008) 71
2. Nashan D., Muller M.L., Grabbe S., Wustlich S., and Enk A. J. Eur. Acad. Derm. Venl. 21 (2007) 1305
3. Carlson J.A., Ross J.S., Slominski A., Linette G., Mysliborski J., Hill J., and Mihm Jr. M. J. Am. Acad. Dermatol. 52 (2005) 743
4. Smalley K.S. Int. J. Cancer 104 (2003) 527
5. Dhawan P., Singh A.B., Ellis D.L., and Richmond A. Cancer Res. 62 (2002) 7335
6. Davies H., Bignell G.R., Cox C., Stephens P., Edkins S., and Clegg S. Nature 417 (2002) 949
7. Houben R., Vetter-Kauczok C.S., Ortmann S., Rapp U.R., Broecker E.B., and Becker J.C. J. Invest. Dermatol. 128 (2008) 2003
8. Eisen T., Ahmad T., Flaherty K.T., Gore M., Kaye S., and Marais R. Br. J. Cancer 95 (2006) 581
9. Smalley K.S.M., Xiao M., Villaneva J., Nguyen T.K., Flaherty K.T., Letrero R., Van Belle P., Elder D.E., Wang Y., Nathanson K.L., and Herlyn M. Oncogene 28 (2009) 85
10. Jilaveanu L., Zito C.R., Aziz S.A., Conrad P.J., Schmitz J.C., Sznol M., Camp R.L., Rimm D.L., and Kluger H.M. Clin. Cancer Res. 15 (2009) 5704
11. Dumaz N., Hayward R., Martin J., Ogilvie L., Hedley D., Curtin J.A., Bastian B.C., Springer C., and Marais R. Cancer Res. 66 (2006) 9483
12. Bennett, M. J. et al. WO2007105058A2.
13. King A.J., Patrick D.R., Batorsky R.S., Ho M.L., Do H.T., Zhang S.Y., Kumar R., Huang P.S., et al. Cancer Res. 23 (2006) 11100
14. Tsai J., Lee J.T., Wang W., Zhang J., Cho H., Bollag G., et al. Proc. Natl. Acad. Sci. 105 (2008) 3041
15. Wilhelm S.M., Adnane L., Newell P., Villanueva A., Llovet J.M., and Lynch M. Mol. Cancer Ther. 7 (2008) 3129
16. Liu Y., and Gray N.S. Nat. Chem. Biol. 2 (2006) 358
17. Voss M.E., Beer C.M., Mitchell S.A., Blmgren P.A., and Zhichkin P.E. Tetrahedron 64 (2008) 645
18. 50 was calculated using GraphPad Prism 4.0 software.
19. 50 determination (MTT assay) was the same as in A375P cell line.
20. Montagut C., Sharma S.V., Shioda T., McDermott U., Ulman M., Ulkus L.E., Dias-Santagata D., Stubbs H., Lee D.Y., Singh A., Drew L., Haber D.A., and Settleman J. Cancer Res. 68 (2008) 4853
21. SM service (www.reactionbiology.com) for screening of 7a.
22. +.