3-[2-(dicyanomethylene)hydrazinyl]benzoic acid | 120814-59-7

• 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: 3-[2-(dicyanomethylene)hydrazinyl]benzoic acid
• 英文别名: 3-[2-(Dicyanomethylidene)hydrazinyl]benzoic acid
• CAS: 120814-59-7
• 化学式: C₁₀H₆N₄O₂
• 分子量: 214.183
• InChiKey: MRYDKRSKDJWGBN-UHFFFAOYSA-N

物化性质

• 沸点：
  414.5±47.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[2-(dicyanomethylene)hydrazinyl]benzoic acid 在 一水合肼 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 3,5-diamino-4-(3-carboxy)phenylazo-pyrazole
  参考文献：
  名称：

  4-Arylazo-3,5-diamino-1H-pyrazole CDK Inhibitors:  SAR Study, Crystal Structure in Complex with CDK2, Selectivity, and Cellular Effects

  摘要：

  In a routine screening of our small-molecule compound collection we recently identified 4-arylazo-3,5-diamino-1H-pyrazoles as a novel group of ATP antagonists with moderate potency against CDK2-cyclin E. A preliminary SAR study based on 35 analogues suggests ways in which the pharmacophore could be further optimized, for example, via substitutions in the 4-aryl ring. Enzyme kinetics studies with the lead compound and X-ray crystallography of an inhibitor-CDK2 complex demonstrated that its mode of inhibition is competitive. Functional kinase assays confirmed the selectivity toward CDKs, with a preference for CDK9cyclin T1. The most potent inhibitor, 4-[(3,5-diamino-1H-pyrazol-4-yl) diazenyl] phenol 31b (CAN508), reduced the frequency of S-phase cells of the cancer cell line HT-29 in antiproliferation assays. Further observed cellular effects included decreased phosphorylation of the retinoblastoma protein and the C-terminal domain of RNA polymerase II, inhibition of mRNA synthesis, and induction of the tumor suppressor protein p53, all of which are consistent with inhibition of CDK9.

  DOI：

  10.1021/jm0605740
• 作为产物：
  描述：

  间氨基苯甲酸 、 丙二腈 在 盐酸 、 sodium nitrite 、 sodium acetate 作用下， 以 甲醇 为溶剂， 反应 3.67h， 生成 3-[2-(dicyanomethylene)hydrazinyl]benzoic acid
  参考文献：
  名称：

  Goncalves, M. Sameiro T.; Oliveira-Campos, Ana M.F.; Rodrigues, Ligia M., Journal of Chemical Research, 2004, # 2, p. 115 - 117

  摘要：

  DOI：

文献信息

• Goncalves, M. Sameiro T.; Oliveira-Campos, Ana M.F.; Rodrigues, Ligia M., Journal of Chemical Research, 2004, # 2, p. 115 - 117
  作者：Goncalves, M. Sameiro T.、Oliveira-Campos, Ana M.F.、Rodrigues, Ligia M.、Proenca, M. Fernanda R.P.、Griffiths, John、Maia, Hernani L.S.、Kaja, Martin、Hrdina, Radim

  DOI：——

  日期：——
• Synthesis of 4-Amino-3,5-dicyano-arylpyrazoles, Part 2: Isolation and Characterization of By-Products
  作者：M. S. T. Gonçalves、A. M. F. Oliveira-Campos、L. M. Rodrigues、M. F. R. P. Proença

  DOI：10.1080/00397911.2010.543304

  日期：2012.6

  Reaction of (dicyanomethylidene-hydrazino) benzoic acids with chloroacetonitrile, under basic conditions, gave cyanomethyl-3-(7-amino-3,5-dicyano-1H-pyrazolo[4,3-d]pyrimidin-1-yl-benzoates and para-substituted cyanomethyl benzoates, in addition to the expected cyanomethyl 3-(4-amino-3,5-dicyano-1H-pyrazol-1-yl)-benzoates.
• 4-Arylazo-3,5-diamino-1<i>H</i>-pyrazole CDK Inhibitors:  SAR Study, Crystal Structure in Complex with CDK2, Selectivity, and Cellular Effects
  作者：Vladimír Kryštof、Petr Cankař、Iveta Fryšová、Jan Slouka、George Kontopidis、Petr Džubák、Marián Hajdúch、Josef Srovnal、Walter F. de Azevedo、Martin Orság、Martina Paprskářová、Jakub Rolčík、Aleš Látr、Peter M. Fischer、Miroslav Strnad

  DOI：10.1021/jm0605740

  日期：2006.11.1

  In a routine screening of our small-molecule compound collection we recently identified 4-arylazo-3,5-diamino-1H-pyrazoles as a novel group of ATP antagonists with moderate potency against CDK2-cyclin E. A preliminary SAR study based on 35 analogues suggests ways in which the pharmacophore could be further optimized, for example, via substitutions in the 4-aryl ring. Enzyme kinetics studies with the lead compound and X-ray crystallography of an inhibitor-CDK2 complex demonstrated that its mode of inhibition is competitive. Functional kinase assays confirmed the selectivity toward CDKs, with a preference for CDK9cyclin T1. The most potent inhibitor, 4-[(3,5-diamino-1H-pyrazol-4-yl) diazenyl] phenol 31b (CAN508), reduced the frequency of S-phase cells of the cancer cell line HT-29 in antiproliferation assays. Further observed cellular effects included decreased phosphorylation of the retinoblastoma protein and the C-terminal domain of RNA polymerase II, inhibition of mRNA synthesis, and induction of the tumor suppressor protein p53, all of which are consistent with inhibition of CDK9.