(E)-tert-butyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylate

• 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: (E)-tert-butyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylate
• 英文别名: (E)-t-butyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylate；tert-butyl (E)-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enoate
• 化学式: C₁₄H₁₅NO₄
• 分子量: 261.277
• InChiKey: OPAGSLHAPPEXHL-UXBLZVDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-tert-butyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylate 在 三氟乙酸 作用下， 反应 1.5h， 以90%的产率得到酪氨酸磷酸化抑制剂 AG 30
  参考文献：
  名称：

  具有体内抗伤害感受活性的首个两孔域钾通道TWIK相关的K +通道1-选择性激动剂的开发。

  摘要：

  TWIK相关的K +通道TREK-1最近已成为开发新型镇痛药的有吸引力的治疗靶标，表明TREK-1的激活可能导致疼痛抑制。在这里，我们报告了一系列取代的丙烯酸（合成1 - 54）基于我们以前的咖啡酸酯酯的工作。通过电生理学评估了类似物调节TREK-1通道的能力以及体内抗伤害感受活性（乙酸诱导的扭体法和热板法），从而鉴定出了一系列能够激活TREK-1的新型分子。并在体内显示出强大的抗伤害感受活性。呋喃基类似物36是该系列中最有前途的。

  DOI：

  10.1021/acs.jmedchem.6b01285
• 作为产物：
  描述：

  氰乙酸叔丁酯 、 3,4-二羟基苯甲醛 在 哌啶 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以52%的产率得到(E)-tert-butyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylate
  参考文献：
  名称：

  具有体内抗伤害感受活性的首个两孔域钾通道TWIK相关的K +通道1-选择性激动剂的开发。

  摘要：

  TWIK相关的K +通道TREK-1最近已成为开发新型镇痛药的有吸引力的治疗靶标，表明TREK-1的激活可能导致疼痛抑制。在这里，我们报告了一系列取代的丙烯酸（合成1 - 54）基于我们以前的咖啡酸酯酯的工作。通过电生理学评估了类似物调节TREK-1通道的能力以及体内抗伤害感受活性（乙酸诱导的扭体法和热板法），从而鉴定出了一系列能够激活TREK-1的新型分子。并在体内显示出强大的抗伤害感受活性。呋喃基类似物36是该系列中最有前途的。

  DOI：

  10.1021/acs.jmedchem.6b01285

文献信息

• PAIN RELIEF COMPOUNDS
  申请人：ECOLE NATIONALE SUPERIEURE DE CHIMIE DE CLERMONT FERRAND

  公开号：US20150038466A1

  公开（公告）日：2015-02-05

  The present invention relates to the use of compounds for the treatment or prevention of pain in mammals, in particularly in human beings, and also to a process for preparing these compounds.

  本发明涉及使用化合物治疗或预防哺乳动物（尤其是人类）的疼痛，并且涉及一种制备这些化合物的方法。
• Benzylidene-malononitrile derivatives for the inhibition of proliferative processes in mammalian cells
  申请人：YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM

  公开号：EP0322738A2

  公开（公告）日：1989-07-05

  There are provided pharmaceutical compositions containing as an active ingredient a compound of the general formula (I): wherein R₁ and R₂ are each independently CN, CONH₂ or COOH or one of R₁ and R₂ may be -CSNH₂ or, when R₁ is CN, R₂ can also be the group R₃ is H, CH₃ or OH, R₄, R₅, R₆, R₇ are each independently H, OH, C₁₋₅ alkyl, C₁₋₅ alkoxy. NH₂, CHO, halogen, NO₂ or COOH, or R₄ and R₅ together may represent a group -O-CH₂-O-; provided that: (a) when R₄ and R₇ are each OH, R₃, R₅ and R₆ are each H and one of R₁ and R₂ is CN, then the other of R₁ and R₂ cannot be CONH₂; and (b) when R₃ and R₇ are each H, R₅ is OH and R₄ and R₆ are both H or both C₁₋₅ alkyl, then R₁ is CN and R₂ is CN or the group or a pharmaceutically acceptable salt thereof. There are also provided some novel compounds of formula (I) above. The compositions and compounds according to the invention are efficient protein-tyrosine kinase inhibitors and are suitable for the inhibition of proliferative processes in mammalian cells.

  提供了含有通式(I)化合物作为活性成分的药物组合物： 其中 R₁ 和 R₂ 各自独立地为 CN、CONH₂ 或 COOH，或者 R₁ 和 R₂ 中的一个可以是 -CSNH₂，或者当 R₁ 是 CN 时，R₂ 也可以是基团 R₃ 是 H、CH₃ 或 OH、 R₄、R₅、R₆、R₇各自独立地为 H、OH、C₁₋₅烷基、C₁₋₅烷氧基。NH₂、CHO、卤素、NO₂或 COOH，或 R₄ 和 R₅ 可共同代表一个基团 -O-CH₂-O-； 条件是(a) 当 R₄ 和 R₇ 均为 OH，R₃、R₅ 和 R₆ 均为 H，且 R₁ 和 R₂ 中的一个为 CN 时，则 R₁ 和 R₂ 中的另一个不能为 CONH₂；(b) 当 R₃ 和 R₇ 分别为 H、R₅ 为 OH 且 R₄ 和 R₆ 均为 H 或均为 C₁₋₅ 烷基时，则 R₁ 为 CN，R₂ 为 CN 或基团 或其药学上可接受的盐。 还提供了一些上述式 (I) 的新型化合物。 根据本发明的组合物和化合物是高效的蛋白酪氨酸激酶抑制剂，适用于抑制哺乳动物细胞的增殖过程。
• Benzylidene- and cinnamylidine-malononitrile derivatives for the inhibition of proliferative processes in mammalian cells
  申请人：YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM

  公开号：EP0614661A2

  公开（公告）日：1994-09-14

  57 There are provided pharmaceutical compositions containing as an active ingredient a compound of the general formula (I): wherein R1 and R2 are each independently CN, CONH2 or COOH or one of R1 ad R2 may be -CSNH2 or, when R1 is CN, R2 can also be the group R3 is H, CH3 or OH, R4, Rs, R6, R7 are each independently H, OH, C1-5 alkyl, C1-5 alkoxy, NH2, CHO, halogen, N02 or COOH, or R4 and R5 together may represent a group -O-CH2-O-; provided that: (a) when R4 ad R7 are each OH, R3, R5 and R6 are each H and one of R1 and R2 is CN, then the other of R1 and R2 cannot be CONH2; and (b) when R3 and R7 are each H, R5 is OH and R4 and R6 are both H or both C1 -5 alkyl, then R1 is CN and R2 is CN or the group or a pharmaceutically acceptable salt thereof. There are also provided some novel compounds of formula (I) above. The compositions and compounds according to the invention are efficient protein-tyrosine kinase inhibitors and are suitable for the inhibition of proliferative processes in mammalian cells.

  57 提供了含有通式（I）化合物作为活性成分的药物组合物： 其中 R1 和 R2 各自独立地为 CN、CONH2 或 COOH，或者 R1 和 R2 中的一个可以是 -CSNH2，或者当 R1 为 CN 时，R2 也可以是基团 R3 是 H、CH3 或 OH、 R4、Rs、R6、R7 各自独立地为 H、OH、C1-5 烷基、C1-5 烷氧基、NH2、CHO、卤素、N02 或 COOH，或 R4 和 R5 可共同代表一个基团 -O-CH2-O-； 条件是(a) 当 R4 和 R7 分别为 OH，R3、R5 和 R6 分别为 H，且 R1 和 R2 中的一个为 CN 时，则 R1 和 R2 中的另一个不能为 CONH2；以及 (b) 当 R3 和 R7 分别为 H，R5 为 OH，且 R4 和 R6 均为 H 或均为 C1-5 烷基时，则 R1 为 CN，R2 为 CN 或该基团 或其药学上可接受的盐。 还提供了一些上述式（I）的新型化合物。 根据本发明的组合物和化合物是高效的蛋白酪氨酸激酶抑制剂，适用于抑制哺乳动物细胞的增殖过程。
• Synthesis and structure–activity relationship study of substituted caffeate esters as antinociceptive agents modulating the TREK-1 channel
  作者：Nuno Rodrigues、Khalil Bennis、Delphine Vivier、Vanessa Pereira、Franck C. Chatelain、Eric Chapuy、Hemantkumar Deokar、Jérôme Busserolles、Florian Lesage、Alain Eschalier、Sylvie Ducki

  DOI：10.1016/j.ejmech.2014.01.049

  日期：2014.3

  The TWIK-related K+ channel, TREK-1, has recently emerged as an attractive therapeutic target for the development of a novel class of analgesic drugs. It has been reported that TREK-1 -/- mice were more sensitive than wild-type mice to painful stimuli, suggesting that activation of TREK-1 could result in pain inhibition. Here we report the synthesis of a series of substituted caffeate esters (12a-u) based on the hit compound CDC 2 (cinnamyl 3,4-dihydroxyl-alpha-cyanocinnamate). These analogs were evaluated for their ability to modulate TREK-1 channel by electrophysiology and for their in vivo antinociceptive activity (acetic acid induced-writhing assay) leading to the identification a series of novel molecules able to activate TREK-1 and displaying potent analgesic activity in vivo. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors
  作者：Aviv Gazit、Pnina Yaish、Chaim Gilon、Alexander Levitzki

  DOI：10.1021/jm00130a020

  日期：1989.10

  A novel class of low molecular weight protein tyrosine kinase inhibitors is described. These compounds constitute a systematic series of molecules with a progressive increase in affinity toward the substrate site of the EGF receptor kinase domain. These competitive inhibitors also effectively block the EGF-dependent autophosphorylation of the receptor. The potent EGF receptor kinase blockers examined were found to competitively inhibit the homologous insulin receptor kinase at 10(2)-10(3) higher inhibitor concentrations in spite of the significant homology between these protein tyrosine kinases. These results demonstrate the ability to synthesize selective tyrosine kinase inhibitors. The most potent EGF receptor kinase inhibitors also inhibit the EGF-dependent proliferation of A431/clone 15 cells with little or no effect on EGF independent cell growth. These results demonstrate the potential use of protein tyrosine kinase inhibitors as selective antiproliferative agents for proliferative diseases caused by the hyperactivity of protein tyrosine kinases. We have suggested the name "tyrphostins" for this class of antiproliferative compounds which act as protein tyrosine kinase blockers.