methyl 2-((S)-2-(3-(3,5-bis(trifluoromethyl)phenyl)ureido)-3,3-dimethylbutanamido)-3-(1-methyl-1H-imidazol-4-yl)propanoate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 2-((S)-2-(3-(3,5-bis(trifluoromethyl)phenyl)ureido)-3,3-dimethylbutanamido)-3-(1-methyl-1H-imidazol-4-yl)propanoate
• 英文别名: methyl (2S)-2-[[(2S)-2-[[3,5-bis(trifluoromethyl)phenyl]carbamoylamino]-3,3-dimethylbutanoyl]amino]-3-(1-methylimidazol-4-yl)propanoate
• 化学式: C₂₃H₂₇F₆N₅O₄
• 分子量: 551.489
• InChiKey: DCYGSPZDKFBZBJ-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  S-(+)-7-Methoxycarbonyl-5,6,7,8-tetrahydroimidazo<1,5-c>pyrimidin-5-on 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 生成 methyl 2-((S)-2-(3-(3,5-bis(trifluoromethyl)phenyl)ureido)-3,3-dimethylbutanamido)-3-(1-methyl-1H-imidazol-4-yl)propanoate
  参考文献：
  名称：

  Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors

  摘要：

  Inhibition of the signaling pathways of signal transducer and activator of transcription 3 (STAT 3) has shown to be a promising strategy to combat cancer. In this paper we report the design, synthesis and evaluation of a novel class of small molecule inhibitors, that is, XZH-5 and its analogues, as promising leads for further development of STAT3 inhibitors. Preliminary SARs was established for XZH-5 and its derivatives; and the binding modes were predicted by molecular docking. Lead compounds with IC50 as low as 6.5 mu M in breast cancer cell lines and 7.6 mu M in pancreatic cancer cell lines were identified. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.025

文献信息

• Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors
  作者：Philias Daka、Aiguo Liu、Chamini Karunaratne、Erika Csatary、Cameron Williams、Hui Xiao、Jiayuh Lin、Zhenghu Xu、Richard C. Page、Hong Wang

  DOI：10.1016/j.bmc.2015.01.025

  日期：2015.3

  Inhibition of the signaling pathways of signal transducer and activator of transcription 3 (STAT 3) has shown to be a promising strategy to combat cancer. In this paper we report the design, synthesis and evaluation of a novel class of small molecule inhibitors, that is, XZH-5 and its analogues, as promising leads for further development of STAT3 inhibitors. Preliminary SARs was established for XZH-5 and its derivatives; and the binding modes were predicted by molecular docking. Lead compounds with IC50 as low as 6.5 mu M in breast cancer cell lines and 7.6 mu M in pancreatic cancer cell lines were identified. (C) 2015 Elsevier Ltd. All rights reserved.