(E)-3-(indol-5-yl)-2-(3,4-dihydroxyphenylcarbonyl)-acrylonitrile

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-(indol-5-yl)-2-(3,4-dihydroxyphenylcarbonyl)-acrylonitrile
• 英文别名: AG 805；2-(3,4-dihydroxybenzoyl)-3-(5-indolyl)-2-propenenitrile；(E)-2-(3,4-dihydroxybenzoyl)-3-(1H-indol-5-yl)prop-2-enenitrile
• 化学式: C₁₈H₁₂N₂O₃
• 分子量: 304.305
• InChiKey: TWEQSBKXFOZXRA-RIYZIHGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  97.1
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-吲哚甲醛 、 氰基甲基-(3,4-二羟基苯基)酮 在 β-丙氨酸 作用下， 反应 3.0h， 以28%的产率得到(E)-3-(indol-5-yl)-2-(3,4-dihydroxyphenylcarbonyl)-acrylonitrile
  参考文献：
  名称：

  Tyrphostins。5.血小板衍生的生长因子受体酪氨酸激酶的有效抑制剂：喹喔啉，喹啉和吲哚酪氨酸受体抑制剂中的结构-活性关系。

  摘要：

  制备了一系列3-吲哚丙烯腈酪氨酸酪蛋白，2-氯-3-苯基喹啉和3-芳基喹喔啉，并测试了其对血小板衍生的生长因子受体酪氨酸激酶（PDGF-RTK）活性的抑制作用。发现抑制剂的效力为喹喔啉>喹啉>吲哚。喹喔啉和喹啉在6和7位上的亲脂基团（甲基，甲氧基）和3位上的苯基对于效价至关重要，而酪蛋白中的亲水邻苯二酚基团在不同位点具有抑制EGFR激酶活性。抑制剂对PDGF具有选择性，对EGF受体和HER-2 / c-ErbB-2受体无活性。

  DOI：

  10.1021/jm950727b

文献信息

• Compounds for the treatment of disorders related to vasculogenesis
  申请人：Yissum Research Development Corp.

  公开号：US05712395A1

  公开（公告）日：1998-01-27

  The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction and particularly KDR/FLK-1 receptor signal transduction in order to regulate and/or modulate vasculogenesis and angiogenesis. The invention is based, in part, on the demonstration that KDR/FLK-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of FLK-1. These results indicate a major role for KDR/FLK-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express FLK-1 and the uses of expressed FLK-1 to evaluate and screen for drugs and analogs of VEGF involved in FLK-1 modulation by either agonist or antagonist activities is also described. The invention also relates to the use of the disclosed compounds in the treatment of disorders, including cancer, diabetes, hemangioma and Kaposi's sarcoma, which are related to vasculogenesis and angiogenesis.

  本发明涉及有机分子，能够调节酪氨酸激酶信号传导，特别是KDR/FLK-1受体信号传导，以调节和/或调控血管生成和血管新生。该发明部分基于KDR/FLK-1酪氨酸激酶受体表达与内皮细胞相关，并鉴定血管内皮生长因子（VEGF）为FLK-1的高亲和配体。这些结果表明KDR/FLK-1在血管生成和血管新生期间的信号系统中起着重要作用。还描述了表达FLK-1的宿主细胞的工程以及利用表达的FLK-1评估和筛选通过激动剂或拮抗剂活性调节FLK-1的VEGF药物和类似物。该发明还涉及使用所披露的化合物治疗与血管生成和血管新生相关的疾病，包括癌症、糖尿病、血管瘤和Kaposi肉瘤。
• Quinazoline compounds and compositions thereof for the treatment of
  申请人：Sugen, Inc.

  公开号：US05792771A1

  公开（公告）日：1998-08-11

  The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction and particularly KDR/FLK-1 receptor signal transduction in order to regulate and/or modulate vasculogenesis and angiogenesis. The invention is based, in part, on the demonstration that KDR/FLK-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of FLK-1. These results indicate a major role for KDR/FLK-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express FLK-1 and the uses of expressed FLK-1 to evaluate and screen for drugs and analogs of VEGF involved in FLK-1 modulation by either agonist or antagonist activities is also described. The invention also relates to the use of the disclosed compounds in the treatment of disorders, including cancer, diabetes, hemangioma and Kaposi's sarcoma, which are related to vasculogenesis and angiogenesis.

  本发明涉及有机分子，能够调节酪氨酸激酶信号传导，特别是KDR/FLK-1受体信号传导，以调节和/或调节血管生成和血管新生。该发明部分基于KDR/FLK-1酪氨酸激酶受体表达与内皮细胞相关，并确定血管内皮生长因子（VEGF）为FLK-1的高亲和力配体的论证。这些结果表明KDR/FLK-1在血管生成和血管新生过程中的信号系统中起着重要作用。描述了表达FLK-1的宿主细胞的工程化，以及利用表达的FLK-1评估和筛选参与FLK-1调节的VEGF的药物和类似物，无论是通过激动剂还是拮抗剂活性。该发明还涉及使用所披露的化合物治疗与血管生成和血管新生相关的疾病，包括癌症、糖尿病、血管瘤和卡波西肉瘤。
• Certain indole compounds which inhibit EGF receptor tyrosine kinase
  申请人：Yissum Research Development Company of the Hebrew University of Jerusalem

  公开号：US05196446A1

  公开（公告）日：1993-03-23

  Heteroarylethenediyl compounds wherein the heteroaryl group can be mono- or icyclic heteroaryl and the aryl group can be or mono- or bicyclic carbocyclic, said compound optionally substituted or polysubstituted, with the proviso that the heteroaryl group is not furyl or thienyl when the ethenediyl group has geminal cyano substituents, and pharmaceutical compositions comprising said compounds, and the use thereof for inhibiting a protein tyrosine kinase portion of a receptor selected from epidermal growth factor and platelet derived growth factor in a patient suffering from such disorder.

  杂环烯丙基化合物，其中杂环芳基基团可以是单环或多环杂环芳基，芳基基团可以是单环或多环碳环芳基，所述化合物可选择性地取代或多取代，但条件是当烯丙基基团具有geminal氰基取代时，杂环芳基基团不是呋喃基或噻吩基。本发明还涉及包含上述化合物的制药组合物，以及将其用于抑制患有此类疾病的患者中的表皮生长因子和血小板源性生长因子中的蛋白酪氨酸激酶部分的受体。
• HETEROCYCLICETHENEDIYL COMPOUNDS WHICH INHIBIT EGF RECEPTOR TYROSINE KINASE
  申请人：RORER INTERNATIONAL (HOLDINGS)

  公开号：EP0527181A1

  公开（公告）日：1993-02-17
• EP0527181A4
  申请人：——

  公开号：EP0527181A4

  公开（公告）日：1993-04-07