2-cyano-3-methoxyhept-2-enenitrile | 35260-98-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-cyano-3-methoxyhept-2-enenitrile
• 英文别名: 2-(1-methoxy-pentylidene)-malonodinitrile；2-(1-Methoxypentylidene)propanedinitrile
• CAS: 35260-98-1
• 化学式: C₉H₁₂N₂O
• 分子量: 164.207
• InChiKey: QIWGPDTVQUDVOM-UHFFFAOYSA-N

物化性质

• 沸点：
  333.3±22.0 °C(Predicted)
• 密度：
  1.004±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  56.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-cyano-3-methoxyhept-2-enenitrile 在 硫酸 、 sodium ethanolate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 20.5h， 生成 3-Butyl-6-methyl-1-(2,4,6-trichloro-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 1-Aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one Inhibitors of Cyclin-Dependent Kinases

  摘要：

  Using a high-throughput screening strategy, a series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation of a protein substrate with IC(50)s in the low micromolar range. On the basis of preliminary structure-activity relationships (SAR), a model was proposed in which these inhibitors occupy the ATP-binding site of the enzyme, forming critical hydrogen bonds to the same residue (Val96) to which the amino group in ATP is presumed to bind. X-ray diffraction studies on a later derivative bound to CDK2 support this binding mode. Iterative cycles of synthesis and screening lead to a novel series of potent, CDK2-selective 6-(arylmethyl)pyrazolopyrimidinones. Placement of a hydrogen-bond donor in the meta-position on the 6-arylmethyl group resulted in approximately 100-fold increases in CDK4 affinity, giving ligands that were equipotent inhibitors of CDK4 and CDK2. These compounds exhibit antiproliferative effects in the NCI HCT116 and other cell lines. The potency of these antiproliferative effects is enhanced in anilide derivatives and translates into tumor growth inhibition in a mouse xenograft model.

  DOI：

  10.1021/jm020455u
• 作为产物：
  描述：

  原戊酸三甲酯 、 丙二腈 在 乙酸酐 作用下， 反应 15.0h， 以90%的产率得到2-cyano-3-methoxyhept-2-enenitrile
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 1-Aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one Inhibitors of Cyclin-Dependent Kinases

  摘要：

  Using a high-throughput screening strategy, a series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation of a protein substrate with IC(50)s in the low micromolar range. On the basis of preliminary structure-activity relationships (SAR), a model was proposed in which these inhibitors occupy the ATP-binding site of the enzyme, forming critical hydrogen bonds to the same residue (Val96) to which the amino group in ATP is presumed to bind. X-ray diffraction studies on a later derivative bound to CDK2 support this binding mode. Iterative cycles of synthesis and screening lead to a novel series of potent, CDK2-selective 6-(arylmethyl)pyrazolopyrimidinones. Placement of a hydrogen-bond donor in the meta-position on the 6-arylmethyl group resulted in approximately 100-fold increases in CDK4 affinity, giving ligands that were equipotent inhibitors of CDK4 and CDK2. These compounds exhibit antiproliferative effects in the NCI HCT116 and other cell lines. The potency of these antiproliferative effects is enhanced in anilide derivatives and translates into tumor growth inhibition in a mouse xenograft model.

  DOI：

  10.1021/jm020455u

文献信息

• WO2006/42850
  申请人：——

  公开号：——

  公开（公告）日：——
• CYANOTHIOPHENE, DEREN HERSTELLUNG UND DEREN VERWENDUNG ALS ARZNEIMITTEL
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP1807411A1

  公开（公告）日：2007-07-18
• [DE] CYANOTHIOPHENE, DEREN HERSTELLUNG UND DEREN VERWENDUNG ALS ARZNEIMITTEL<br/>[EN] CYANOTHIOPHENES, THE PRODUCTION THEREOF AND THEIR USE AS MEDICAMENTS<br/>[FR] CYANOTHIOPHENES, LEUR PRODUCTION ET LEUR UTILISATION COMME MEDICAMENTS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2006042850A1

  公开（公告）日：2006-04-27

  [EN] The invention relates to cyanothiophenes of general formula (I), in which the R's are defined in the claims, and relates to their tautomers, stereoisomers, mixtures and salts that have valuable pharmacological properties, in particular, a glucagon receptor-antagonistic action.
  [FR] L'invention concerne des cyanothiophènes, de formule générale (I) dans laquelle les R sont tels que définis dans les revendications, ainsi que leurs tautomères, leurs stéréoisomères, leurs mélanges et leurs sels présentant des propriétés pharmacologiques précieuses, en particulier, un effet antagoniste du récepteur de Glugacon.
  [DE] Die vorliegende Erfindung betrifft Cyanothiophene der allgemeinen Formel (I), in der R wie in den Ansprüchen definiert sind, deren Tautomere, deren Stereoisomere, deren Gemische und deren Salze, welche wertvolle pharmakologische Eigenschaften aufweisen, insbesondere eine Glugacon-Rezeptor-antagonistische Wirkung.