Synthesis and biological activity of 1H-pyrrol-2(5H)-ones
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摘要: 目的 研究5位连有取代苯基的1H-吡咯-2(5H)-酮类化合物生物活性。 方法 在吡咯酮的5位引入各种取代苯基,合成出目标化合物,所有化合物1H NMR和MS等谱确证;通过荧光偏振法测定化合物对蛋白的抑制常数Ki。 结果 所有13个目标化合物都能抑制蛋白的结合,其中化合物4e的Ki达到阳性对照药的5倍。 结论 5位苯环的取代基团对活性影响很大,吸电子基团取代活性高于亲电子基团,其中硝基取代活性最强。
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关键词:
- 1H-吡咯-2(5H)-酮 /
- 化学合成 /
- 生物活性
Abstract: Objective To study the biological activity of 1H-pyrrol-2(5H)-ones which introduced substituted phenyl group as side chain. Methods By introduction of 5-substituted phenyl group, a serial 1H-pyrrol-2(5H)-ones were synthesized and their structures were confirmed by 1H NMR and MS. The binding constant Ki was assayed by the fluorescence polarization binding assay method. Results Thirteen title compounds exhibited stronger protein binding activities and compound 4e showed five times higher than positive drug. Conclusion The introduction of electron-attracting groups was beneficial to improve their activities. Among them, the nitro group was preferred group.-
Key words:
- 1H-pyrrol-2(5H)-one /
- chemical synthesis /
- biological activity
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[1] Moll UM, Petrenko O. The MDM2-p53 Interaction[J]. Mol Cancer Res,2003, 1:1001. [2] Kussie PH, Gorina S, Marechal V, et al. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain[J]. Science, 1996, 274:948. [3] Garcia-Echeverria C, Chene P, Blommers MJJ. Discovery of potent antagonists of the interaction between human double minute 2 and tumor suppressor p53[J].J Med Chem, 2000, 43:3205. [4] Baek S, Kutchukian PS, Verdine GL, et al. Structure of the stapled p53 peptide bound to Mdm2[J].J Am Chem Soc, 2012, 134:103. [5] Lyubomir T, Vassilev BT, Bradford G, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2[J]. Science, 2004, 303:844. [6] Yu S, Qin D, Shangary S, et al. Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction[J]. J Med Chem, 2009, 52:7970. [7] Marugan JJ, Leonard K, Raboisson P, et al. Enantiomerically pure 1,4-benzo-diazepine-2,5-diones as MDM2 antagonists[J]. Bioorg Med Chem Lett, 2006,16:3115. -
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