Synthesis and biological activity of 2-aminothiazoles as novel inhibitors of PGE2 production in cells.
作者： Breland Smith , Hui-Hua Chang , Federico Medda , Vijay Gokhale , Justin Dietrich
DOI: 10.1016/J.BMCL.2012.03.013
关键词:
摘要: Abstract This Letter presents the synthesis and biological evaluation of a collection 2-aminothiazoles as novel class compounds with capability to reduce production PGE 2 in HCA-7 human adenocarcinoma cells. A total 36 analogs were synthesized assayed for reduction, those potent cellular activity counter screened inhibitory against COX-2 cell free assay. In general, bearing 4-phenoxyphenyl substituent R position highly active cells while maintaining negligible inhibition. Specifically, compound 5l (R 1 = Me, = 4-OPh-Ph, 3 = CH(OH)Me) exhibited most reducing entire series (EC 50 = 90 nM) an IC value inhibition >5 μM vitro. Furthermore, anti-tumor analog 1a was analyzed xenograft mouse models exhibiting promising anti-cancer activity.
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sci-hub.se 参考文章(17)
Adel Hamza, Xinyun Zhao, Min Tong, Hsin-Hsiung Tai, Chang-Guo Zhan, Novel human mPGES-1 inhibitors identified through structure-based virtual screening Bioorganic & Medicinal Chemistry. ,vol. 19, pp. 6077- 6086 ,(2011) , 10.1016/J.BMC.2011.08.040
Jong Taik Moon, Ji Young Jeon, Hang Ah Park, Young-Soo Noh, Kyung-Tae Lee, Jungahn Kim, Dong Joon Choo, Jae Yeol Lee, Synthesis and PGE2 production inhibition of 1H-furan-2,5-dione and 1H-pyrrole-2,5-dione derivatives Bioorganic & Medicinal Chemistry Letters. ,vol. 20, pp. 734- 737 ,(2010) , 10.1016/J.BMCL.2009.11.067
Bernard Côté, Louise Boulet, Christine Brideau, David Claveau, Diane Ethier, Richard Frenette, Marc Gagnon, André Giroux, Jocelyne Guay, Sébastien Guiral, Joseph Mancini, Evelyn Martins, Frédéric Massé, Nathalie Méthot, Denis Riendeau, Joel Rubin, Daigen Xu, Hongping Yu, Yves Ducharme, Richard W. Friesen, Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitors Bioorganic & Medicinal Chemistry Letters. ,vol. 17, pp. 6816- 6820 ,(2007) , 10.1016/J.BMCL.2007.10.033
André Giroux, Louise Boulet, Christine Brideau, Anh Chau, David Claveau, Bernard Côté, Diane Ethier, Richard Frenette, Marc Gagnon, Jocelyne Guay, Sébastien Guiral, Joseph Mancini, Evelyn Martins, Frédéric Massé, Nathalie Méthot, Denis Riendeau, Joel Rubin, Daigen Xu, Hongping Yu, Yves Ducharme, Richard W. Friesen, Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors Bioorganic & Medicinal Chemistry Letters. ,vol. 19, pp. 5837- 5841 ,(2009) , 10.1016/J.BMCL.2009.08.085
Thomas D. Penning, John J. Talley, Stephen R. Bertenshaw, Jeffery S. Carter, Paul W. Collins, Stephen Docter, Matthew J. Graneto, Len F. Lee, James W. Malecha, Julie M. Miyashiro, Roland S. Rogers, D. J. Rogier, Stella S. Yu, Gary D. Anderson, Earl G. Burton, J. Nita Cogburn, Susan A. Gregory, Carol M. Koboldt, William E. Perkins, Karen Seibert, Amy W. Veenhuizen, Yan Y. Zhang, Peter C. Isakson, Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide (SC-58635, celecoxib). Journal of Medicinal Chemistry. ,vol. 40, pp. 1347- 1365 ,(1997) , 10.1021/JM960803Q
Douglas Hanahan, Robert A Weinberg, The hallmarks of cancer. Cell. ,vol. 100, pp. 57- 70 ,(2000) , 10.1016/S0092-8674(00)81683-9
Dingzhi Wang, Raymond N. DuBois, Eicosanoids and cancer Nature Reviews Cancer. ,vol. 10, pp. 181- 193 ,(2010) , 10.1038/NRC2809
Denis Riendeau, Renee Aspiotis, Diane Ethier, Yves Gareau, Erich L. Grimm, Jocelyne Guay, Sébastien Guiral, Hélène Juteau, Joseph A. Mancini, Nathalie Méthot, Joel Rubin, Richard W. Friesen, Inhibitors of the inducible microsomal prostaglandin E2 synthase (mPGES-1) derived from MK-886 Bioorganic & Medicinal Chemistry Letters. ,vol. 15, pp. 3352- 3355 ,(2005) , 10.1016/J.BMCL.2005.05.027
Douglas Hanahan, Robert A. Weinberg, Hallmarks of cancer: the next generation. Cell. ,vol. 144, pp. 646- 674 ,(2011) , 10.1016/J.CELL.2011.02.013
Moana Tercel, Ralph J Stevenson, Guo-Liang Lu, Stephen M Stribbling, William R Wilson, Michele A Tatnell, Rebecca N Marnane, Kathleen G Mountjoy, William A Denny, None, Weight loss effects of quaternary salts of 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indoles; structure–activity relationships Bioorganic & Medicinal Chemistry. ,vol. 20, pp. 734- 749 ,(2012) , 10.1016/J.BMC.2011.12.007