tert-butyl (E)-3-(4-iodophenyl)but-2-enoate | 1247847-51-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: tert-butyl (E)-3-(4-iodophenyl)but-2-enoate
• CAS: 1247847-51-3
• 化学式: C₁₄H₁₇IO₂
• 分子量: 344.192
• InChiKey: NJIAPGUVMDZFDD-MDZDMXLPSA-N

物化性质

• 沸点：
  363.4±21.0 °C(Predicted)
• 密度：
  1.422±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  tert-butyl (E)-3-(4-iodophenyl)but-2-enoate 在 4-二甲氨基吡啶 、 碘代三甲硅烷 、 2,2,2-三氟-N,N-二(三甲硅基)乙酰胺 、 silver nitrate 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 sodium hydroxide 、 镉 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 109.0h， 生成 pentachlorophenyl (2E)-3-[4-[[bis[(2,2-dimethyl-1-oxopropoxy)methoxy]phosphinyl]difluoromethyl]phenyl]but-2-enoate
  参考文献：
  名称：

  Potent and Selective Phosphopeptide Mimetic Prodrugs Targeted to the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 3

  摘要：

  Signal transducer and activator of transcription 3 (Stat3), a target for anticancer drug design, is activated by recruitment to phosphotyrosine residues on growth factor and cytokine receptors via its SH2 domain. We report here structure activity relationship studies on phosphopeptide mimics targeted to the SH2 domain of Stat3. Inclusion of a methyl group on the beta-position of the pTyr mimic 4-phosphocinnamide enhanced affinity 2- to 3-fold. Bis-pivaloyloxymethyl prodrugs containing beta-methylcinnamide, dipeptide scaffolds Haic and Nle-cis-3,4-methanoproline, and glutamine surrogates were highly potent, completely inhibiting phosphorylation of Stat3 Tyr705 at 0.5-1,mu M in a variety of cancer cell lines. The inhibitors were selective for Stat3 over Stat1, Stat5, Src, and p85 of PI3K, indicating ability to discriminate individual SH2 domains in intact cells. At concentrations that completely inhibited Stat3 phosphorylation, the prodrugs were not cytotoxic to a panel of tumor cells, thereby showing clear distinction between cytotoxicity and effects downstream of activated Stat3.

  DOI：

  10.1021/jm2000882
• 作为产物：
  描述：

  4-碘代苯乙酮 、 二乙基膦酰基乙酸叔丁酯 在 lithium tert-butoxide 作用下， 以 四氢呋喃 、 正己烷 、 叔丁醇 为溶剂， 反应 1.0h， 以79%的产率得到tert-butyl (E)-3-(4-iodophenyl)but-2-enoate
  参考文献：
  名称：

  Potent and Selective Phosphopeptide Mimetic Prodrugs Targeted to the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 3

  摘要：

  Signal transducer and activator of transcription 3 (Stat3), a target for anticancer drug design, is activated by recruitment to phosphotyrosine residues on growth factor and cytokine receptors via its SH2 domain. We report here structure activity relationship studies on phosphopeptide mimics targeted to the SH2 domain of Stat3. Inclusion of a methyl group on the beta-position of the pTyr mimic 4-phosphocinnamide enhanced affinity 2- to 3-fold. Bis-pivaloyloxymethyl prodrugs containing beta-methylcinnamide, dipeptide scaffolds Haic and Nle-cis-3,4-methanoproline, and glutamine surrogates were highly potent, completely inhibiting phosphorylation of Stat3 Tyr705 at 0.5-1,mu M in a variety of cancer cell lines. The inhibitors were selective for Stat3 over Stat1, Stat5, Src, and p85 of PI3K, indicating ability to discriminate individual SH2 domains in intact cells. At concentrations that completely inhibited Stat3 phosphorylation, the prodrugs were not cytotoxic to a panel of tumor cells, thereby showing clear distinction between cytotoxicity and effects downstream of activated Stat3.

  DOI：

  10.1021/jm2000882

文献信息

• [EN] ESTROGEN RECEPTOR MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS DE RÉCEPTEURS D'OESTROGÈNES ET LEURS UTILISATIONS
  申请人：SERAGON PHARMACEUTICALS INC

  公开号：WO2013142266A1

  公开（公告）日：2013-09-26

  Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

  本文描述了一些雌激素受体调节剂化合物。还描述了包括本文描述的化合物在内的药物组合物和药物，以及使用这些雌激素受体调节剂的方法，单独或与其他化合物结合，用于治疗与雌激素受体介导或依赖的疾病或症状。
• ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
  申请人：Seragon Pharmaceuticals, Inc.

  公开号：US20150105403A1

  公开（公告）日：2015-04-16

  Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

  本文描述了一些雌激素受体调节剂化合物。还描述了包括上述化合物的制药组合物和药物，以及使用这些雌激素受体调节剂，单独或与其他化合物联合治疗介导或依赖于雌激素受体的疾病或病情的方法。
• [EN] INHIBITORS OF STAT3 AND USES THEREOF<br/>[FR] INHIBITEURS DU STAT3 ET LEURS UTILISATIONS
  申请人：UNIV TEXAS

  公开号：WO2010118309A3

  公开（公告）日：2011-01-13
• US9499538B2
  申请人：——

  公开号：US9499538B2

  公开（公告）日：2016-11-22