AG 537 | 140674-77-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: AG 537
• 英文别名: tyrphostin AG 537；2-cyano-N-{3-[2-cyano-3-(3,4-dihydroxyphenyl)-acryloylamino]-propyl}-3-(3,4-dihydroxyphenyl)-acrylamide；bis-tyrphostin；(E)-2-cyano-N-[3-[[(E)-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino]propyl]-3-(3,4-dihydroxyphenyl)prop-2-enamide
• CAS: 140674-77-7
• 化学式: C₂₃H₂₀N₄O₆
• 分子量: 448.435
• InChiKey: ZHOKHSGWBNPFQU-GONBZBRSSA-N

物化性质

• 沸点：
  901.7±65.0 °C(Predicted)
• 密度：
  1.461±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  187
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  乙酰氯 、 AG 537 在 4-二甲氨基吡啶 吡啶 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 生成
  参考文献：
  名称：

  [EN] METHODS AND AGENTS FOR INHIBITING DYNAMIN-DEPENDENT ENDOCYTOSIS
  [FR] PROCEDES ET AGENTS POUR INHIBER L'ENDOCYTOSE DEPENDANT DE LA DYNAMINE

  摘要：

  抑制细胞中依赖动力蛋白的内吞作用的方法已被披露，包括将细胞用式(I)的化合物、二聚酪酪激酶抑制剂、生理上可接受的盐或其前药的有效量进行处理。还提供了所述方法中有用的化合物。抑制细胞中依赖动力蛋白的内吞作用适用于治疗癫痫和神经系统疾病和症状。

  公开号：

  WO2005049009A1
• 作为产物：
  描述：

  2-cyano-N-[3-(2-cyanoacetylamino)propyl]acetamide 、 3,4-二羟基苯甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以85%的产率得到AG 537
  参考文献：
  名称：

  Parallel Solution-Phase Synthesis of Targeted Tyrphostin Libraries with Anticancer Activity

  摘要：

  半自动化、优雅的合成和并行溶液相合成方法的结合，使我们开发出了五个有针对性的对称酪磷脂化合物库。这些化合物库平均由 12 个化合物组成。尽管如此，我们还是发现了针对 HT29（结直肠癌）和 G401（肾癌）细胞系的低微摩尔强效生长抑制剂。此外，我们还获得了重要的 SAR 数据。我们注意到，具有 2-氯苯基的类似物始终具有最强的生长抑制活性（10：GI50 HT29 5.5 ± 0.4 μM，GI50 G401 2.6 ± 0.4 μM；23：GI50 HT29 2.4 ± 0.2 μM，GI50 G401 1.9 ± 1 μM；34：GI50 HT29 8.8 ± 0.2 μM，GI50 G401 1.9 ± 1 μM）：对于 34：GI50 HT29 8.8 ± 3.1 μM，GI50 G401 6.2 ± 2.9 μM；对于 46：GI50 HT29 5.2 ± 0.9 μM，GI50 G401 3.7 ± 0.6 μM；对 57：GI50 HT29 4.6 ± 0.8 μM，GI50 G401 2.1 ± 0.2 μM）、3-氯苯（对 11：GI50 HT29 3.8 ± 0.7 μM，GI50 G401 1.7 ± 0.7 μM；对于 48：GI50 HT29 5.9 ± 0.1 μM，GI50 G401 3.4 ± 0.6 μM；对于 58：GI50 HT29 4.8 ± 0.9 μM，GI50 G401 3.4 ± 0.2 μM），或 3-甲氧基苯基取代基（对于 13：GI50 HT29 7.4 ± 3.8 μM，GI50 G401 2.8 ± 0.5 μM；对于 26：对于 26：GI50 HT29 4.5 ± 0.5 μM，GI50 G401 4.9 ± 1 μM；对于 37：GI50 HT29 3.7 ± 0.2 μM，GI50 G401 1.6 ± 0.2 μM；49：GI50 HT29 3.7 ± 0.4 μM，GI50 G401 3.4 ± 0.2 μM；60：GI50 HT29 4.1 ± 0.6 μM，GI50 G401 1.8 ± 0.3 μM）。最后，我们注意到，增加末端芳香环之间的距离对 2-、3-氯苯基和 3-甲氧基苯基类似物的影响很小，但对 OH、COOH 和多重取代的类似物有有利影响。

  DOI：

  10.1071/ch04143

文献信息

• Parallel Solution-Phase Synthesis of Targeted Tyrphostin Libraries with Anticancer Activity
  作者：Timothy A. Hill、Jennette A. Sakoff、Phillip J. Robinson、Adam McCluskey

  DOI：10.1071/ch04143

  日期：——

  The combination of semi-automation, an elegant synthesis, and parallel solution-phase synthesis approaches has allowed the development of five targeted, symmetrical tyrphostin compound libraries. These libraries on average are comprised of 12 compounds. Notwithstanding this, low micromolar potent growth inhibitors against HT29 (colorectal carcinoma) and G401 (renal carcinoma) cell lines were discovered. Additionally, significant SAR data was obtained. We noted that the most potent growth inhibitory activity was consistently observed for those analogues that possessed a 2-chlorophenyl (for 10: GI50 HT29 5.5 ± 0.4 μM, GI50 G401 2.6 ± 0.4 μM; for 23: GI50 HT29 2.4 ± 0.2 μM, GI50 G401 1.9 ± 1 μM; for 34: GI50 HT29 8.8 ± 3.1 μM, GI50 G401 6.2 ± 2.9 μM; for 46: GI50 HT29 5.2 ± 0.9 μM, GI50 G401 3.7 ± 0.6 μM; for 57: GI50 HT29 4.6 ± 0.8 μM, GI50 G401 2.1 ± 0.2 μM), a 3-chlorophenyl (for 11: GI50 HT29 3.8 ± 0.7 μM, GI50 G401 1.7 ± 0.7 μM; for 48: GI50 HT29 5.9 ± 0.1 μM, GI50 G401 3.4 ± 0.6 μM; for 58: GI50 HT29 4.8 ± 0.9 μM, GI50 G401 3.4 ± 0.2 μM), or a 3-methoxyphenyl substituent (for 13: GI50 HT29 7.4 ± 3.8 μM, GI50 G401 2.8 ± 0.5 μM; for 26: GI50 HT29 4.5 ± 0.5 μM, GI50 G401 4.9 ± 1 μM; for 37: GI50 HT29 3.7 ± 0.2 μM, GI50 G401 1.6 ± 0.2 μM; for 49: GI50 HT29 3.7 ± 0.4 μM, GI50 G401 3.4 ± 0.2 μM; for 60: GI50 HT29 4.1 ± 0.6 μM, GI50 G401 1.8 ± 0.3 μM). Finally, we noted that increasing the distance between the terminal aromatic rings had only a minimal effect on the 2-, 3-chlorophenyl, and 3-methoxyphenyl analogues, but did have a favourable effect on OH, COOH, and multiply substituted analogues.

  半自动化、优雅的合成和并行溶液相合成方法的结合，使我们开发出了五个有针对性的对称酪磷脂化合物库。这些化合物库平均由 12 个化合物组成。尽管如此，我们还是发现了针对 HT29（结直肠癌）和 G401（肾癌）细胞系的低微摩尔强效生长抑制剂。此外，我们还获得了重要的 SAR 数据。我们注意到，具有 2-氯苯基的类似物始终具有最强的生长抑制活性（10：GI50 HT29 5.5 ± 0.4 μM，GI50 G401 2.6 ± 0.4 μM；23：GI50 HT29 2.4 ± 0.2 μM，GI50 G401 1.9 ± 1 μM；34：GI50 HT29 8.8 ± 0.2 μM，GI50 G401 1.9 ± 1 μM）：对于 34：GI50 HT29 8.8 ± 3.1 μM，GI50 G401 6.2 ± 2.9 μM；对于 46：GI50 HT29 5.2 ± 0.9 μM，GI50 G401 3.7 ± 0.6 μM；对 57：GI50 HT29 4.6 ± 0.8 μM，GI50 G401 2.1 ± 0.2 μM）、3-氯苯（对 11：GI50 HT29 3.8 ± 0.7 μM，GI50 G401 1.7 ± 0.7 μM；对于 48：GI50 HT29 5.9 ± 0.1 μM，GI50 G401 3.4 ± 0.6 μM；对于 58：GI50 HT29 4.8 ± 0.9 μM，GI50 G401 3.4 ± 0.2 μM），或 3-甲氧基苯基取代基（对于 13：GI50 HT29 7.4 ± 3.8 μM，GI50 G401 2.8 ± 0.5 μM；对于 26：对于 26：GI50 HT29 4.5 ± 0.5 μM，GI50 G401 4.9 ± 1 μM；对于 37：GI50 HT29 3.7 ± 0.2 μM，GI50 G401 1.6 ± 0.2 μM；49：GI50 HT29 3.7 ± 0.4 μM，GI50 G401 3.4 ± 0.2 μM；60：GI50 HT29 4.1 ± 0.6 μM，GI50 G401 1.8 ± 0.3 μM）。最后，我们注意到，增加末端芳香环之间的距离对 2-、3-氯苯基和 3-甲氧基苯基类似物的影响很小，但对 OH、COOH 和多重取代的类似物有有利影响。
• Methods and Agents for Inhibiting Dynamin-Dependent Endocytosis
  申请人：McCluskey Adam

  公开号：US20070225363A1

  公开（公告）日：2007-09-27

  There are disclosed methods for inhibiting dynamin-dependent endocytosis in cells comprising treating the cells with an effective amount of a compound of formula (I), or a dimeric tyrphostin, physiologically acceptable salt, or prodrug thereof. Compounds useful in the methods described are also provided. The inhibition of dynamin-dependent endocytosis of cells is applicable to the treatment of epilepsy and neurological disorders and conditions.

  本文揭示了抑制细胞中依赖于动力蛋白的内吞作用的方法，其中包括使用化合物(I)、二聚酪氨酸酪氨酸激酶抑制剂、生理可接受的盐或前药的有效量处理细胞。本文还提供了适用于所述方法的化合物。抑制细胞中依赖于动力蛋白的内吞作用适用于治疗癫痫和神经系统疾病和症状。
• Use of endocytosis inhibitors and antibodies for cancer therapy
  申请人：THE UNIVERSITY OF QUEENSLAND

  公开号：US10253107B2

  公开（公告）日：2019-04-09

  The present invention relates to the use of endocytosis inhibitors, including clathrin-dependent endocytosis inhibitors such as inhibitors of dynamin and antibodies, for enhancing the immune response to cancer, and thereby treating cancers including cancer associated receptor positive cancers.

  本发明涉及内吞抑制剂的使用，包括凝集素依赖性内吞抑制剂，例如达纳明抑制剂和抗体，用于增强对癌症的免疫反应，从而治疗癌症，包括癌症相关受体阳性癌症。
• T5 exonuclease-based method to identify DNA topoisomerase inhibitors
  申请人：Leng Fenfei

  公开号：US11268129B1

  公开（公告）日：2022-03-08

  The present invention provides assays and methods for studying DNA topology and topoisomerases. The assays and methods utilize a circular plasmid DNA comprising one or more hairpin structures and the ability of T5 exonuclease (T5E) to digest the circular plasmid DNA in a specific configuration. The assays and methods can be used as a high throughput screening for inhibitors of, for example, DNA gyrases and DNA topoisomerases I for anticancer drug and antibiotics discovery.

  本发明提供了研究DNA拓扑结构和拓扑异构酶的检测方法。这些检测方法利用包含一个或多个发夹结构的环状质粒 DNA 以及 T5 外切酶（T5E）以特定构型消化环状质粒 DNA 的能力。这些检测方法可用于高通量筛选 DNA 回旋酶和 DNA 拓扑异构酶 I 等的抑制剂，以发现抗癌药物和抗生素。
• Tyrphostins. 6. Dimeric Benzylidenemalononitrile Tyrphostins:  Potent Inhibitors of EGF Receptor Tyrosine Kinase <i>in Vitro</i>
  作者：Aviv Gazit、Nir Osherov、Chaim Gilon、Alexander Levitzki

  DOI：10.1021/jm960225d

  日期：1996.1.1

  Benzylidenemalononitrile (BMN) tyrphostins were previously found to be potent inhibitors of EGF receptor (EGFR) tyrosine kinase activity. Since these compounds were found to compete for the substrate and sometimes with the ATP site and since EGFR acts as a dimer, we prepared a series of dimeric tyrphostins. These dimeric tyrphostins were built from two BMN units linked by various spacers and designed to fit the dimeric cross-autophosphorylation signal transduction intermediate of the EGFR tyrosine kinases. Structure-activity relationship of these potent dimeric EGF receptor tyrosine kinase inhibitors is reported.