酪氨酸磷酸化抑制剂A63 | 5553-97-9

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 酪氨酸类衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 酪氨酸磷酸化抑制剂A63
• 中文别名: 4-羟基苄基丙二腈
• 英文名称: Tyrphostin A63
• 英文别名: 2-(4-hydroxybenzyl)malononitrile；4-hydroxybenzylmalononitrile；tyrphostin AG43；AG43；(4-hydroxy-benzyl)-malononitrile；(4-Hydroxy-benzyl)-malononitril；2-[(4-Hydroxyphenyl)methyl]propanedinitrile
• CAS: 5553-97-9
• 化学式: C₁₀H₈N₂O
• mdl: MFCD00133904
• 分子量: 172.186
• InChiKey: PDRLQWJJFLVIRC-UHFFFAOYSA-N

物化性质

• 稳定性/保质期：

  遵照规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  67.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  酪氨酸磷酸化抑制剂A63 在 一水合肼 作用下， 以 甲醇 为溶剂， 反应 8.0h， 以60%的产率得到4-[(3,5-diamino-1H-pyrazol-4-yl)methyl]phenol
  参考文献：
  名称：

  The Synthesis of Some Derivatives Based on the 4-Benzyl-1H-pyrazole-3,5-diamine Core

  摘要：

  The three-step synthesis of 4-benzyl-1H-pyrazole-3,5-diamines 2 from commercially available aldehydes 3 is given. The Knoevenagel condensation was utilized to assemble the initial carbon framework, resulting in the benzylidenemalononitriles 4 which were directly transformed by the reduction of the electron deficient C=C bond to benzylmalononitriles 5. Subsequent cycloaddition of hydrazine with 5 afforded the desired pyrazoles 2. Due to the high similarity with 4-arylazo-1H-pyrazole-3,5-diamines, the biological activities of the 4-benzyl-1H-pyrazole-3,5-diamines 2 were evaluated while focusing on the inhibition of cyclin-dependent kinases (CDKs), but no significant results were obtained.

  DOI：

  10.3987/com-10-12101
• 作为产物：
  描述：

  4-羟基苯亚甲基丙二腈 在 Penicillium citrinum CBMAI 1186 作用下， 以 二甲基亚砜 为溶剂， 反应 144.0h， 以12%的产率得到酪氨酸磷酸化抑制剂A63
  参考文献：
  名称：

  海洋真菌柠檬青霉CBMAI 1186的合成及生物催化的Knoevenagel缩合化合物的烯还原反应

  摘要：

  α，β-不饱和化合物的化学选择性生物还原是一种重要的合成工具，可用于合成许多精细化学品和药物分子。本文报道了在绿色化学条件下使用甲醇（如溶剂，游离碱和游离催化剂）通过微波辐射通过Knoevenagel缩合合成芳族丙二腈衍生物。在成瘾中，还测试了海洋来源的真菌柠檬青霉CBMAI 1186的全细胞对芳香族丙二腈衍生物的C–C双键的生物催化还原作用。真菌烯还原酶催化的产物以非常好的收率获得（高达> 98％）。

  DOI：

  10.1016/j.tet.2016.02.014

文献信息

• Monosubstituted Malononitriles: Efficient One-Pot Reductive Alkylations of Malononitrile with Aromatic Aldehydes
  作者：Robert Sammelson、Fariba Tayyari、Dwight Wood、Phillip Fanwick

  DOI：10.1055/s-2007-990945

  日期：2008.1

  been developed for the reductive alkylation of malononitrile with aromatic aldehydes. This new procedure has vastly improved the yield and efficiency of the process, and increased the scope of the aromatic aldehydes. Incorporating water as the catalyst in ethanol for the condensation step allows stoichiometric amounts of malononitrile and aldehyde to be employed. The reduction step takes place quickly

  已经开发了一种强大的新一锅法，用于丙二腈与芳香醛的还原烷基化。这种新工艺极大地提高了工艺的产率和效率，并扩大了芳香醛的范围。在缩合步骤的乙醇中加入水作为催化剂允许使用化学计量的丙二腈和醛。还原步骤用硼氢化钠快速有效地进行，通过过滤或萃取得到单取代的丙二腈。2-喹啉甲醛的产物迅速重排为新的中氮茚，而单取代衍生物的烷基化提供了不重排的不对称二取代丙二腈。
• A novel bifunctional Pd–ZIF-8/rGO catalyst with spatially separated active sites for the tandem Knoevenagel condensation–reduction reaction
  作者：Hefang Wang、Yansu Wang、Aizhong Jia、Cunyue Wang、Luming Wu、Yongfang Yang、Yanji Wang

  DOI：10.1039/c7cy01725a

  日期：——

  microscopy (SEM) and transmission electron microscopy (TEM). Pd–ZIF-8/rGO shows excellent catalytic performance in the tandem reaction with 100% benzaldehyde conversion and 98.3% selectivity to benzylmalononitrile. The excellent catalytic performance of Pd–ZIF-8/rGO in the tandem reaction is due to the high catalytic activities of spatially separated Pd NPs and ZIF-8 active sites and concentrated reactants

  通过分别在氧化石墨烯（GO）表面上共价相互作用和沸石咪唑酸酯骨架（ZIF-8）的配位作用固定钯纳米颗粒（NPS），制备了一种具有空间分离的活性位点的新型双功能催化剂。作为Knoevenagel缩合-串联反应的有效催化剂。傅里叶变换红外光谱（FT-IR），X射线衍射（XRD），拉曼光谱，紫外可见光谱，X射线光电子能谱（XPS）和热重分析（TGA）的结果表明，Pd和ZIF-8被成功地固定在GO的表面，并使用NaBH 4将GO还原为还原的氧化石墨烯（rGO）在制备Pd–ZIF-8 / rGO中用作还原剂。N 2表征了Pd–ZIF-8 / rGO的组织结构和形貌。吸附-解吸，扫描电子显微镜（SEM）和透射电子显微镜（TEM）。Pd–ZIF-8 / rGO在串联反应中表现出出色的催化性能，苯甲醛转化率为100％，对苄基丙二腈的选择性为98.3％。Pd–ZIF-8 / rGO在串联反应中的出色催化性能是由于空间分离的Pd
• Nanocrystalline ZnO forKnoevenagel Condensation and Reduction of the Carbon,Carbon Double Bond in Conjugated Alkenes
  作者：Mona Hosseini-Sarvari、Hashem Sharghi、Samane Etemad

  DOI：10.1002/hlca.200890072

  日期：2008.4

  A novel efficient and eco-friendly nanocrystalline ZnO catalyst was used for the Knoevenagel condensation and for the reduction of CC double bonds at room temperature in the absence of solvents.

  新型高效，环保的纳米ZnO催化剂用于Knoevenagel缩合反应，并在室温下在无溶剂的情况下还原CC双键。
• Pesticide composition comprising malononitrile compounds
  申请人：——

  公开号：US20040142821A1

  公开（公告）日：2004-07-22

  The present invention relates to use of malononitrile compounds of formula (X): 1 wherein R 1 and R 2 are the same or different and independently C 1 -C 5 (halo)-alkyl, C 1 -C 5 (halo)alkyloxy, C 2 -C 5 (halo)alkenyl, C 2 -C 5 (halo)alkynyl, hydrogen, or cyano; R 3 and R 4 are the same or different and independently C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, or hydrogen, or R 3 and R 4 are taken together to form C 2 -C 6 (halo)alkylene or C 4 -C 6 (halo)alkenylene; R 5 is halogen, cyano, nitro, C 1 -C 4 (halo)alkyl, or the like; n is an integer of 0 to 4; R 6 is halogen, cyano, nitro, C 1 -C 4 (halo)alkyl, or the like; or R 5 and R 6 are taken together to form methylenedioxy; with the provisos that when R 6 is hydrogen, then n is an integer of 1 to 4 and that when n is 2 or more, then R 5 's are different from each other; as pesticides, and to pesticide compositions containing these compounds as active ingredients. The present invention makes it possible to effectively control pests such as insect pests, acarine pests, and nematode pests.

  本发明涉及使用式（X）的丙二腈化合物：其中R1和R2相同或不同且独立地为C1-C5（卤）烷基，C1-C5（卤）烷氧基，C2-C5（卤）烯基，C2-C5（卤）炔基，氢或氰基；R3和R4相同或不同且独立地为C1-C10烷基，C2-C10烯基，C2-C10炔基或氢，或者R3和R4结合形成C2-C6（卤）烷基或C4-C6（卤）烯基；R5为卤素，氰基，硝基，C1-C4（卤）烷基或类似物；n为0至4的整数；R6为卤素，氰基，硝基，C1-C4（卤）烷基或类似物；或者R5和R6结合形成亚甲二氧基；但当R6为氢时，n为1至4的整数，且当n为2或更多时，R5不相同；作为杀虫剂，以及含有这些化合物作为活性成分的杀虫剂组合物。本发明使得能够有效地控制害虫，例如昆虫害虫，螨虫害虫和线虫害虫。
• Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: Synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II
  作者：Hriday Bera、Probir kumar Ojha、Bee Jen Tan、Lingyi Sun、Anton V. Dolzhenko、Wai-Keung Chui、Gigi Ngar Chee Chiu

  DOI：10.1016/j.ejmech.2014.03.063

  日期：2014.5

  In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones were designed, synthesized and evaluated for their TP inhibitory potential. All the synthesized analogues conferred a varying degree of TP inhibitory activity, comparable or better than positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 mu M). A systematic approach to the lead optimization identified compounds 3c and 4a as the most promising TP inhibitors, exhibiting mixed mode of enzyme inhibition. Moreover, selected compounds demonstrated the ability to attenuate the expression of the angiogenic markers (viz. MMP-9 and VEGF) in MDA-MB-231 cells at sublethal concentrations. In addition, molecular docking studies revealed the plausible binding orientation of these inhibitors towards TP, which was in accordance with the experimental results. Taken as a whole, these compounds would constitute a new direction for the design of novel TP inhibitors with promising antiangiogenic properties. (C) 2014 Elsevier Masson SAS. All rights reserved.