α-Hydroxy-4-methyl-benzyliden-malonsaeure-dinitril | 5515-09-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: α-Hydroxy-4-methyl-benzyliden-malonsaeure-dinitril
• 英文别名: 2-Cyan-3-hydroxy-3-p-tolyl-acrylonitril；2-[Hydroxy-(4-methylphenyl)methylidene]propanedinitrile
• CAS: 5515-09-3
• 化学式: C₁₁H₈N₂O
• 分子量: 184.197
• InChiKey: VGQMAXLZZVLYAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  67.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  α-Hydroxy-4-methyl-benzyliden-malonsaeure-dinitril 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-methylphenyl)-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：

  对甲基苯甲酰氯 、 丙二腈 在 sodium hydroxide 作用下， 生成 α-Hydroxy-4-methyl-benzyliden-malonsaeure-dinitril
  参考文献：
  名称：

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

  摘要：

  DOI：

文献信息

• PROTEIN KINASE INHIBITORS
  申请人：Pharmascience, Inc.

  公开号：US20150191473A1

  公开（公告）日：2015-07-09

  The present invention relates to a novel family of inhibitors of protein kinases. In particular, the present invention relates to inhibitors of the members of the Tec and Src protein kinase families.

  本发明涉及一种新型的蛋白激酶抑制剂家族。具体而言，本发明涉及Tec和Src蛋白激酶家族成员的抑制剂。
• 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：——
• 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：——
• US9796716B2
  申请人：——

  公开号：US9796716B2

  公开（公告）日：2017-10-24
• 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
  作者：Cristina Tintori、Giuseppina La Sala、Giulia Vignaroli、Lorenzo Botta、Anna Lucia Fallacara、Federico Falchi、Marco Radi、Claudio Zamperini、Elena Dreassi、Lucia Dello Iacono、Donata Orioli、Giuseppe Biamonti、Mirko Garbelli、Andrea Lossani、Francesca Gasparrini、Tiziano Tuccinardi、Ilaria Laurenzana、Adriano Angelucci、Giovanni Maga、Silvia Schenone、Chiara Brullo、Francesca Musumeci、Andrea Desogus、Emmanuele Crespan、Maurizio Botta

  DOI：10.1021/acs.jmedchem.5b00140

  日期：2015.6.11

  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.