α-cyano-β-hydroxy-p-methoxycinnamonitrile | 5515-10-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: α-cyano-β-hydroxy-p-methoxycinnamonitrile
• 英文别名: α-Hydroxy-4-methoxy-benzyliden-malonsaeure-dinitril；2-Cyan-3-hydroxy-3-<4-methoxy-phenyl>-acrylonitril；(p-Methoxy-benzoyl)-malo-dinitrilenol；2-[Hydroxy-(4-methoxyphenyl)methylidene]propanedinitrile
• CAS: 5515-10-6
• 化学式: C₁₁H₈N₂O₂
• 分子量: 200.197
• InChiKey: QQXSKJIGOYTWAF-UHFFFAOYSA-N

物化性质

• 熔点：
  187-188 °C(Solv: chloroform (67-66-3))
• 沸点：
  351.8±42.0 °C(Predicted)
• 密度：
  1.264±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  77
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2926909090

反应信息

• 作为反应物：
  描述：

  α-cyano-β-hydroxy-p-methoxycinnamonitrile 以 四氢呋喃 、 mineral oil 为溶剂， 反应 10.0h， 生成 5-amino-1-(2-hydroxy-2-phenylethyl)-3-(4-methoxyphenyl)-1Hpyrazole-4-carbonitrile
  参考文献：
  名称：

  Studies on the ATP Binding Site of Fyn Kinase for the Identification of New Inhibitors and Their Evaluation as Potential Agents against Tauopathies and Tumors

  摘要：

  Fyn is a member of the Src-family of nonreceptor protein-tyrosine kinases. Its abnormal activity has been shown to be related to various human cancers as well as to severe pathologies,; such as Alzheimer's and Parkinson's diseases. Herein, a structure-based drug design protocol was employed aimed at identifying novel Fyn inhibitors. Two hits from commercial sources (1, 2) were found active against Fyn with K-i of about 2 mu M, while derivative 4a, derived from our internal library, showed a K-i of 0.9 mu M. A hit-to-lead optimization effort was then initiated on derivative 4a to improve its potency. Slightly modifications rapidly determine an increase in the binding affinity, with the best inhibitors 4c and 44 having K(i)s of 70 and 95 nM, respectively. Both compounds were found able to inhibit the phosphorylation of : the protein Tau in an Alzheimer's model cell line and showed antiproliferative activities against different cancer cell lines.

  DOI：

  10.1021/acs.jmedchem.5b00140
• 作为产物：
  描述：

  大茴香酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 、 苯 为溶剂， 生成 α-cyano-β-hydroxy-p-methoxycinnamonitrile
  参考文献：
  名称：

  Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm00130a020

文献信息

• Libis,B.; Fleury,J.-P., Bulletin de la Societe Chimique de France, 1965, p. 3323 - 3329
  作者：Libis,B.、Fleury,J.-P.

  DOI：——

  日期：——
• Pyrrole derivatives as potent inhibitors of lymphocyte-specific kinase: Structure, synthesis, and SAR
  作者：Tetsuo Takayama、Hiroki Umemiya、Hideaki Amada、Tetsuya Yabuuchi、Fumiyasu Shiozawa、Hironori Katakai、Akiko Takaoka、Akie Yamaguchi、Mayumi Endo、Masakazu Sato

  DOI：10.1016/j.bmcl.2009.11.014

  日期：2010.1

  We have described the synthesis, enzyme inhibitory activity, structure-activity relationships, and proposed binding mode of a novel series of pyrrole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <10 nM) for Lck kinase inhibition. (C) 2009 Elsevier Ltd. All rights reserved.
• Fleury,J.-P.; Libis,B., Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1963, vol. 256, p. 2419 - 2421
  作者：Fleury,J.-P.、Libis,B.

  DOI：——

  日期：——
• Yokoyama, Masataka; Sato, Kenzi; Tateno, Hideo, Journal of the Chemical Society. Perkin transactions I, 1987, p. 623 - 628
  作者：Yokoyama, Masataka、Sato, Kenzi、Tateno, Hideo、Hatanaka, Hidekatsu

  DOI：——

  日期：——
• GAZIT, AVIV;YAISH, PNINA;GILON, CHAIM;LEVITZKI, ALEXANDER, J. MED. CHEM., 32,(1989) N0, C. 2344-2352
  作者：GAZIT, AVIV、YAISH, PNINA、GILON, CHAIM、LEVITZKI, ALEXANDER

  DOI：——

  日期：——