(4-hydroxyphenyl)carbonohydrazonoyl dicyanide | 55966-85-3

• 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: (4-hydroxyphenyl)carbonohydrazonoyl dicyanide
• 英文别名: Propanedinitrile, [(4-hydroxyphenyl)hydrazono]-；2-[(4-hydroxyphenyl)hydrazinylidene]propanedinitrile
• CAS: 55966-85-3
• 化学式: C₉H₆N₄O
• 分子量: 186.173
• InChiKey: XTCRJLBGLWCFIH-UHFFFAOYSA-N

物化性质

• 熔点：
  95 °C
• 沸点：
  359.0±44.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-hydroxyphenyl)carbonohydrazonoyl dicyanide 在 一水合肼 作用下， 生成 4-[(3,5-diamino-1H-pyrazol-4-yl)hydrazinylidene]cyclohexa-2,5-dien-1-one
  参考文献：
  名称：

  A Facile Synthesis of New Monoazo Disperse Dyes Derived from 4-Hydroxyphenylazopyrazole-5-amines: Evaluation of Microwave Assisted Dyeing Behavior

  摘要：

  合成了一系列含有吡唑并嘧啶部分的新型单偶氮分散染料，通过将马隆腈或3-氨基克罗顿腈与4-羟基苯基重氮盐酸盐偶联。将所得产物与水合肼处理，得到相应的4-芳基偶氮氨基吡唑，然后与2,4-戊二酮和烯胺腈或芳基取代的烯胺酮反应，生成目标吡唑并嘧啶单偶氮分散染料。使用NMR光谱和X射线晶体学方法对染料的结构进行了表征。采用微波辐射加热的高温染色方法，进行聚酯织物的染色。大多数染色织物在光牢度测试中表现出中等的光牢度以及优良的洗涤和汗液牢度水平。

  DOI：

  10.3390/molecules171213891
• 作为产物：
  描述：

  对氨基苯酚 、 丙二腈 在 盐酸 、 sodium acetate 、 sodium nitrite 作用下， 生成 (4-hydroxyphenyl)carbonohydrazonoyl dicyanide
  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

• Modification of Boc-Protected CAN508 via Acylation and Suzuki-Miyaura Coupling
  作者：Martin Pisár、Eva Schütznerová、Filip Hančík、Igor Popa、Zdeněk Trávníček、Petr Cankař

  DOI：10.3390/molecules23010149

  日期：——

  derivatives were further arylated by Suzuki-Miyaura coupling using the XPhos Pd G2 pre-catalyst. The coupling reaction provided generally the para-substituted benzoylpyrazoles in the higher yields than the meta-substituted ones. The Boc groups were only utilized as directing functionalities for the benzoylation step and were hydrolyzed under conditions of Suzuki-Miyaura coupling, which allowed for elimination

  细胞周期蛋白依赖性激酶抑制剂 CAN508 用二碳酸二叔丁酯保护以接触氨基苯甲酰化吡唑。溴衍生物通过 Suzuki-Miyaura 偶联使用 XPhos Pd G2 预催化剂进一步芳基化。偶联反应通常以比间位取代的更高的产率提供对位取代的苯甲酰基吡唑。Boc 基团仅用作苯甲酰化步骤的导向官能团，并在 Suzuki-Miyaura 偶联条件下水解，从而消除了额外的脱保护步骤。
• Utilization of DmbNHNH2 in the synthesis of amino-substituted 4-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenols
  作者：Eva Schütznerová、Igor Popa、Vladimír Kryštof、Hiroyuki Koshino、Zdeněk Trávníček、Pavel Hradil、Petr Cankař

  DOI：10.1016/j.tet.2012.03.063

  日期：2012.5

  (2,4-Dimethoxybenzyl)hydrazine (DmbNHNH(2)) was utilized in the synthesis of Dmb-protected 4-((3,5diamino-1H-pyrazol-4-yl)diazenyl)phenols. This unambiguous protection of the pyrazole endocyclic nitrogen atom enabled the preparation of amino-substituted 4((3,5-diamino-1H-pyrazol-4yl)diazenyl) phenols that were inaccessible through direct substitution. The Boc group could be selectively cleaved in the presence of the Dmb group. (C) 2012 Elsevier Ltd. All rights reserved.

  (2,4-二甲氧基苄基)肼(DmbNHNH₂)用于合成Dmb保护的4-((3,5-二氨基-1H-吡唑-4-基)偶氮基)苯酚。这种明确的吡唑环内氮原子保护使得能够制备氨基取代的4-((3,5-二氨基-1H-吡唑-4-基)偶氮基)苯酚，这些化合物无法通过直接取代获得。在Dmb基团存在下，Boc基团可以被选择性裂解。©2012 Elsevier Ltd.所有权利保留。
• Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors
  作者：Aviv Gazit、Pnina Yaish、Chaim Gilon、Alexander Levitzki

  DOI：10.1021/jm00130a020

  日期：1989.10

  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.
• 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：——
• 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.