2-(2-(dicyanomethylene)hydrazinyl) benzoic acid | 98749-23-6

• 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: 2-(2-(dicyanomethylene)hydrazinyl) benzoic acid
• 英文别名: 2-(2-carboxyphenylhydrazo)malononitrile；2-[2-(Dicyanomethylidene)hydrazinyl]benzoic acid
• CAS: 98749-23-6
• 化学式: C₁₀H₆N₄O₂
• 分子量: 214.183
• InChiKey: RQHWLNIWNUNYDJ-UHFFFAOYSA-N

物化性质

• 沸点：
  399.0±44.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 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：

  2-(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-(2-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：

  邻氨基苯甲酸 、 丙二腈 在 盐酸 、 sodium nitrite 、 sodium acetate 作用下， 以 水 为溶剂， 反应 0.5h， 生成 2-(2-(dicyanomethylene)hydrazinyl) benzoic acid
  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

文献信息

• In Situ Ligand Transformation in the Synthesis of Manganese Complexes: Mono-, Tri- and a Barrel-shaped Tetradeca-nuclear Mn^II₁₄Aggregate
  作者：Muhammad Usman Anwar、Yanhua Lan、Lianne M. C. Beltran、Rodolphe Clérac、Sven Pfirrmann、Christopher E. Anson、Annie K. Powell

  DOI：10.1021/ic9001048

  日期：2009.6.15

  amination of DHB resulting from the nucleophilic attack of an amino group of ethylenediamine. The linear, mixed-valence trinuclear complex, (Et3NH)4[MnIII2MnII(μ-OH)2(Lig-II)2(HLig-II)2] (2), was synthesized using a preparation involving the in situ reaction of azide and a nitrile of DHB. Larger species can also be prepared using this technique. In a reaction involving two different in situ ligand formations

  给出了导致一例原位配体转化的三个例子的三个一锅合成法。这些原位反应涉及2-（N'-二氰基亚甲基-肼基）-苯甲酸（DHB）的各种转化。由此产生的配体能够制备三种新的配位化合物，并通过红外光谱，元素分析和单晶X射线衍射对其进行了全面表征。通过一锅合成制备[Mn III（Lig-I）（CH 3 OH）Cl]（1）配合物，其中通过胺化反应形成芳基配体（Lig-I）2-由乙二胺的氨基发生亲核攻击而产生的DHB。线性，混合价三核复合物，（Et 3使用涉及叠氮化物和DHB腈的原位反应的制剂合成了NH）4 [Mn III 2 Mn II（μ-OH）2（Lig-II）2（HLig-II）2 ]（2）。也可以使用该技术制备更大的物种。在涉及两个不同原位配体形成的反应中，两个DHB分子的环缩合和DHB腈的部分水解（四癸核Mn（II）聚集体的第一个实例（H 3 O）4 [Mn II 14（ μ 6 -CO 3）（μ
• Cooperative Metal–Ligand Assisted<i>E/Z</i>Isomerization and Cyano Activation at Cu^IIand Co^IIComplexes of Arylhydrazones of Active Methylene Nitriles
  作者：Kamran T. Mahmudov、Maximilian N. Kopylovich、Alessandra Sabbatini、Michael G. B. Drew、Luísa M. D. R. S. Martins、Claudio Pettinari、Armando J. L. Pombeiro

  DOI：10.1021/ic501704g

  日期：2014.9.15

  (NaHL3) were used in the template synthesis of a series of CuII and CoII complexes [Cu(H2O)2L1a]·H2O (1), [Cu(H2O)(3-pyon)L1b]·H2O (2), [Cu(H2O)(4-pyon)L1b] (3), [Co(H2O)((CH3)2NCHO)(μ-L2a)]2·(CH3)2NCHO (4), [Cu3(μ3-OH)(NO3)(CH3OH)(μ2-X)3(μ2-HL3)] (5), [Cu(H2O)(py)L3]·H2O (6), [Cu(H2O)2(μ-L4)]6·6H2O (7), [Cu(2-cnpyb)2(L1b)2]·2H2O (8), [Cu(2-cnpya)2(L1a)2]·2H2O (9), and [Cu(H2O)(4-cnpy)(L1a)2] (10), where

  新的（E / Z）-2-（2-（1-氰基-2-甲氧基-2-氧亚乙基）肼基）苯甲酸（H 2 L 4）和已知的2-（2-（二氰基亚甲基）肼基）苯磺酸钠（ NaHL 1），2-（2-（二氰基亚甲基）肼基）苯甲酸（H 2 L 2）和钠（E / Z）-2-（2-（1-氰基-2-甲氧基-2-氧代乙叉））肼基）苯磺酸盐（NaHL 3）用于模板合成一系列Cu II和Co II配合物[Cu（H 2 O）2 L 1a ]·H 2 O（1），[Cu（H 2 O） （3 on）L图1b ]·H 2 O（2），[铜（H 2 O）（4-pyon）L- 1B ]（3），[CO（H 2 O）（（CH 3）2 NCHO）（μ-L 2A） ] 2 ·（CH 3）2 NCHO（4），[铜3（μ 3 -OH）（NO 3）（CH 3 OH）（μ 2 -X）3（μ 2 -HL 3）]（5）， [Cu（H 2 O）（py）L 3 ]·H
• Template Syntheses of Copper(II) Complexes from Arylhydrazones of Malononitrile and their Catalytic Activity towards Alcohol Oxidations and the Nitroaldol Reaction: Hydrogen Bond-Assisted Ligand Liberation and<i>E</i>/<i>Z</i>Isomerisation
  作者：Maximilian N. Kopylovich、Archana Mizar、M. Fátima C. Guedes da Silva、Tatiana C. O. Mac Leod、Kamran T. Mahmudov、Armando J. L. Pombeiro

  DOI：10.1002/chem.201203254

  日期：2013.1.7

  treated with ethylenediamine. The hydrogen bond‐induced E/Z isomerization of the (HL1d)− ligand occurs upon conversion of [Na(H2O)2(μ‐H2O)2}(HL1d)]n (14) to [Cu(H2O)6][HL1d]2⋅2 H2O (15) and [CuNa(H2O)‐(κN1,1 κO2:2 κO1 L1d)2}K0.5(μ‐O)2]n⋅H2O (16). The synthesized complexes 3–9 are catalyst precursors for both the selective oxidation of primary and secondary alcohols (to the corresponding carbonyl compounds)

  将2-一锅模板缩合（2-（二氰基亚甲基）肼基）苯磺酸（H 2大号1，1），或2-（2-（二氰基亚甲基）肼基）苯甲酸（H 2大号2，2）用甲醇（一），乙二胺（b）中，乙醇（c）或铜的水（d）（II），导致了各种金属配合物，即，单核物[Cu（H 2 O）2（κ ø 1，κ ñ 2 大号1A ]（3）和[铜（H 2 O）（κ Ô 1，κ ñ 3 大号1B）]（4），四核物[Cu 4（1κ Ò 1，κ Ñ 2：2κ ø 1 大号图2a）3 - （1κ Ò 1，κ Ñ 2：2κ ø 2 大号2A）]（5），[铜2（H 2 O）（1κ Ò 1，κ ñ 2：2κ ø 1 大号2C） - （1κ Ò 1，1κ ñ 2：2κ Ô 1，2κ ñ 1 L -图2c）] 2（6）和物[Cu 2（H 2 O）2（κ ø 1，κ Ñ 2 L - 1DD） - （1κ Ò 1，κ Ñ 2：2κ ø 1 大号1DD）（μ-
• Novel cyano-activated Cu(<scp>ii</scp>) complexes of arylhydrazones of active methylene nitriles and their catalytic application for azide–alkyne cycloaddition in water and glycerol
  作者：Atash V. Gurbanov、Abdallah G. Mahmoud、Vusala A. Aliyeva、M. Fátima C. Guedes da Silva、Armando J. L. Pombeiro

  DOI：10.1039/d3nj00512g

  日期：——

  characterized by elemental analyses, electrospray ionization mass spectrometry (ESI-MS), and FT-IR spectroscopy. Their molecular structures were established using single crystal X-ray diffraction (SCXRD) analysis. The catalytic activity of the complexes was investigated for the microwave assisted 1,3-dipolar azide–alkyne cycloaddition reaction using a mixture of water and glycerol as reaction medium. Pre-catalyst

  2-(2-(二氰基亚甲基)肼基)苯甲酸 (H 2 L 1 ) 与乙酸铜 ( II ) 在咪唑 (im)、4,4'-联吡啶 (4,4'- bipy) 或吡啶 (py) 导致新配合物 [Cu 2 (CH 3 OH) 2 (μ-L 1a ) 2 ] ( 1 ), [Cu(L 1a )(im)] ( 2 ), [Cu( L 1a )(H 2 O)(4,4'-bipy)]·H 2 O ( 3 ) 或 [Cu(L 1a )(py)] n ( 4 )，其中 (L 1a )2− = ( Z )-1-(2-carboxylatophenyl)-2-(1-cyano-2-imino-2-methoxyethylidene)hydrazin-1-ide。在甲醇中存在吡啶的情况下，醋酸铜 ( II ) 一水合物与 2-(2-(二氰亚甲基)肼基)对苯二甲酸(H 3 L 2 ) 反应中的腈基一锅法活化得到三核 Cu (
• 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.