Novel benzoylurea derivatives as potential antitumor agents; synthesis, activities and structure-activity relationships

Archives of Pharmacal Research - Tập 25 - Trang 781-785 - 2002
Ki -Jun Hwang1, Kyung -Ho Park2, Chong -Ock Lee3, Beom -Tae Kim1
1Department of Chemistry, and Research Center of Bioactive Materials, College of Natural Science, Chonbuk National University, Chonju, Korea
2Dupont CR&D, Experimental Station, Wilmington, USA
3Screening & Toxicology Research Center, Korea Research Institute of Chemical Technology, Yusung, Korea

Tóm tắt

A series of pyrazoloxyphenyl benzoyl urea derivatives was designed and synthesized for cytotoxic evaluation as potential antitumor agents. The synthetic compounds were evaluated for in vitro cytotoxicity against five human tumor cell lines, including A-549, SKOV-3, SK-MEL-2, XF-498 and HCT-15. Among others, compound 11 exhibited 50~100 times greater antitumor activities than the commercial product, Cisplatin.

Tài liệu tham khảo

Chern, J. W., Leu, Y., Wang, S., Jou, R., Lee, C.F., Tsou, P.C., Hsu, S.C., Liaw, Y.C. and Lin, H.M., Synthesis and cytotoxic evaluation of substituted sulfonyl-N-hydroxyguanidine derivatives as potential antitumor agents.J. Med. Chem., 40, 2276–2286 (1997). Gaede, B. and McDermott, L. L., Novel Perfluoroalkyl-substituted pyrazoles.J. Heterocyclic Chem., 30, 49–54 (1993). Howbert, J. J., Grossman, S. Crowel, T.A., Rieder, B. J., Harper, R. W., Kramer, K. E. Tao, E. V., Aikins, J., Poore, G. A., Rinzel, S. M., Grindey, G. B., Shaw, W. N., and Todd, G. C., Novel agents effective against solid tumor: The arylsulf-onylureas. synthesis, activities, and analysis of QSAR.J. Med. Chem., 3, 2393–2407 (1990). Hwang, K. J. and Park, K. H. pyrazole derivatives,US patent 5430158 (1995). Hwang, K. J. and Park, K. H. pyrazole containing benzoylurea derivatives, composition and use,EP 0557481 (1997). Iwata, S., Namekata, J., Tanaka, K. and Mitsuhashi, K., Synthesis of 4-Hydroxy-3-trifiuoromethypyrazoles.J. Heterocyclic Chem., 28, 1971–1976 (1991). Kondo, N., Iwao, T., Masuda, H., Yamanouchi, K., Ishihara, Y., Yamada, N., Haga, T., Ogawa, Y. and Yokoyama, K., Improved oral absorption of a poorly water-soluble drug, HO-221.Chem. Pharm. Bull. 41 (4), 737–740 (1993). Okada, H., Koyanagi, T., Yamada, N. and Haga, T., Synthesis and antitumor activies of novel benzoylphenylurea. derivatives.Chem. Pharm. Bull., 39 (9), 2308–2315 (1991). Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J. B., Vistica, D. T., Warren, J. T., Bokesch, H., Kenn, S. and Boyd, M. R.,J. Natl. Cancer Inst., 82, 1107 (1990). Wright, J. E. and Retrakaran, A. (eds.), Chitin and Benzoyl-phenyl ureas, Dr. W. Junk publishers, Dordrecht, (1987).