(2E)-2-氰基-3-(3,4-二羟基苯基)-N-(3-苯基丙基)-2-丙烯酰胺 | 133550-34-2

• 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
• 中文名称: (2E)-2-氰基-3-(3,4-二羟基苯基)-N-(3-苯基丙基)-2-丙烯酰胺
• 英文名称: tyrphostin B46
• 英文别名: Tyrphostin B 46；(E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-(3-phenyl-propyl)-3-propenamide；(E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-(3-phenylpropyl)acrylamide；AG 555；AG555；α-cyano-(3,4-dihydroxy)-N-(3-phenylpropyl)cinnamide；Tyrphostin AG 555；(E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-(3-phenylpropyl)prop-2-enamide
• CAS: 133550-34-2
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: GSQOBTOAOGXIFL-LFIBNONCSA-N

物化性质

• 沸点：
  621.1±55.0 °C(Predicted)
• 密度：
  1.273±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO或乙醇：可溶

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  93.4
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• WGK Germany：
  3
• 安全说明：
  S22,S24/25
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  -20℃

制备方法与用途

生物活性

AG-555（Tyrphostin B46）是一种酪氨酸激酶抑制剂，能够与拓扑异构酶I直接相互作用，从而阻止DNA松弛。其IC50值为0.7 μM，可以抑制EGFR。

靶点

Target	Value
EGFR (Cell-free assay)	0.7 μM

体外研究

AG-555（100 μM）能够同时抑制病毒生命周期的早期阶段（整合过程）和晚期阶段（病毒蛋白合成）。Tyrphostin AG555通过阻断Cdk2激活，诱导非肿瘤细胞在G1-S期和早期S期生长停滞，并对EGFR过表达细胞的生长具有很强的抑制效果。此外，AG 555能够特异性地通过MAPK途径激活及结合磷酸化的Jun/ATF-2于一个新的内源性调控序列来抑制BPV-1转录。

细胞增殖测定

参数	值
细胞系:	NIH/3T3未感染细胞和慢性感染Mo-MuLV的NIH/3T3细胞。
浓度:	100 μM。
孵育时间:	1小时。
结果:	抑制了Mo-MuLV前病毒DNA整合。

反应信息

• 作为产物：
  描述：

  3-苯基-1-丙胺 反应 16.0h， 生成 (2E)-2-氰基-3-(3,4-二羟基苯基)-N-(3-苯基丙基)-2-丙烯酰胺
  参考文献：
  名称：

  Tyrphostins. II. Heterocyclic and .alpha.-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine kinases

  摘要：

  We have previously described a novel series of low molecular weight protein tyrosine kinase inhibitors which we named tyrphostins. The characteristic active pharmacophore of these compounds was the hydroxy-cis-benzylidenemalononitrile moiety. In this article we describe three novel groups of tyrphostins: (i) one group has the phenolic moiety of the cis-benzylidenemalononitrile replaced either with other substituted benzenes or with heteroaromatic rings, (ii) another is a series of conformationally constrained derivatives of hydroxy-cis-benzylidenemalononitriles in which the malononitrile moiety is fixed relative to the aromatic ring, and (iii) two groups of compounds in which the position trans to the benzenemalononitrile has been substituted by ketones and amides. Among the novel tyrphostins examined we found inhibitors which discriminate between the highly homologous EGF receptor kinase (HER1) and ErbB2/neu kinase (HER2). These findings may lead to selective tyrosine kinase blockers for the treatment of diseases in which ErbB2/neu is involved.

  DOI：

  10.1021/jm00110a022

文献信息

• Tissue non-specific alkaline phosphatase inhibitors and uses thereof for treating vascular calcification
  申请人：Burnham Institute for Medical Research

  公开号：EP2433496A1

  公开（公告）日：2012-03-28

  Disclosed herein are compounds that are tissue-nonspecific alkaline phosphatase inhibitors. The disclosed compounds are used to treat, prevent, or abate vascular calcification, arterial calcification and other cardiovascular diseases.

  本文公开的化合物是组织非特异性碱性磷酸酶抑制剂。所公开的化合物可用于治疗、预防或减轻血管钙化、动脉钙化和其他心血管疾病。
• Antipsychotic molecular-targeting epithelial growth factor receptor
  申请人：Nawa Hiroyuki

  公开号：US20060167026A1

  公开（公告）日：2006-07-27

  The purpose of this invention is to provide an agent useful for prevention and/or treatment of psychosis, schizophrenia and cognitive impairments. To solve this problem, this invention provides epidermal growth factor receptor inhibitors as therapeutic agents for psychosis, schizophrenia and cognitive impairments.

  本发明的目的是提供一种用于预防和/或治疗精神病、精神分裂症和认知障碍的药物。为了解决这个问题，本发明提供了表皮生长因子受体抑制剂作为治疗精神病、精神分裂症和认知障碍的药物。
• TISSUE NON-SPECIFIC ALKALINE PHOSPHATASE INHIBITORS AND USES THEREOF FOR TREATING VASCULAR CALCIFICATION
  申请人：The Burnham Institute for Medical Research

  公开号：EP2164329A2

  公开（公告）日：2010-03-24
• Modulation of Axon Degeneration
  申请人：Watts Ryan

  公开号：US20110256150A1

  公开（公告）日：2011-10-20

  The invention relates generally to treatment of neurological disorders and nervous system injuries. The invention specifically provides methods of using modulators of particular target proteins to modulate degeneration of neurons or portions thereof, such as axons.
• MODULATION OF AXON DEGENERATION
  申请人：Genentech, Inc.

  公开号：US20140328940A1

  公开（公告）日：2014-11-06

  The invention relates generally to treatment of neurological disorders and nervous system injuries. The invention specifically provides methods of using modulators of particular target proteins to modulate degeneration of neurons or portions thereof, such as axons.