4-hydroxy-N’-[(E)-(5-chloro-2-hydroxyphenyl)methylidene]benzohydrazide | 1227627-03-3

• 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-hydroxy-N’-[(E)-(5-chloro-2-hydroxyphenyl)methylidene]benzohydrazide
• 英文别名: N'-[(E)-(5'-chloro-2'-hydroxylphenyl)methylidene]-4-hydroxylbenzohydrazide；(E)-N'-(5-chloro-2-hydroxybenzylidene)-4-hydroxybenzohydrazide；AD4-1017；N'-(5-Chloro-2-hydroxybenzylidene)-4-hydroxybenzohydrazide；N-[(E)-(5-chloro-2-hydroxyphenyl)methylideneamino]-4-hydroxybenzamide
• CAS: 1227627-03-3
• 化学式: C₁₄H₁₁ClN₂O₃
• 分子量: 290.706
• InChiKey: YEGJSEASBVRYIO-LZYBPNLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  81.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-羟基苯甲酰肼 、 5-氯代水杨醛 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以75.6%的产率得到4-hydroxy-N’-[(E)-(5-chloro-2-hydroxyphenyl)methylidene]benzohydrazide
  参考文献：
  名称：

  Thymidine phosphorylase and prostrate cancer cell proliferation inhibitory activities of synthetic 4-hydroxybenzohydrazides: In vitro, kinetic, and in silico studies

  摘要：

  胸苷磷酸化酶（TP）的过度表达在许多病理并发症中发挥了关键作用，包括导致癌细胞增殖的血管生成。因此，在寻找新的抗癌药物过程中，合成了一系列4-羟基苯肼 (1–29)，并评估了其体外胸苷磷酸化酶抑制活性。二十种化合物（1–3，6–14，16，19，22–24，和27–29）显示出从强到弱的TP抑制活性，其IC50值范围为6.8到229.5 μM，且与标准药物如tipiracil（IC50 = 0.014 ± 0.002 μM）和7-脱氮黄嘌呤（IC50 = 41.0 ± 1.63 μM）相比。对选定抑制剂3、9、14、22、27和29的动力学研究表明，存在非竞争性和无竞争性抑制模式。这些抑制剂的分子对接研究显示它们能够与TP的别构位点中的氨基酸残基相互作用，包括Asp391、Arg388和Leu389。活性化合物的抗增殖（细胞毒性）活性也在小鼠成纤维细胞（3T3）和前列腺癌（PC3）细胞系上进行了评估。化合物1、2、19以及22–24对PC3细胞表现出抗增殖活性，其IC50值在6.5到10.5 μM之间，而对3T3（小鼠成纤维细胞）细胞增殖则基本上没有细胞毒性。因此，本研究识别出一种新的TP和癌细胞增殖的双重抑制剂类别，值得进一步研究以开发抗癌药物。

  DOI：

  10.1371/journal.pone.0227549

文献信息

• [EN] SUBSTITUTED (E)-N'-(1-PHENYLETHYLIDENE) BENZOHYDRAZIDE ANALOGS AS HISTONE DEMETHYLASE INHIITORS<br/>[FR] ANALOGUES DE (E)-N'-(1-PHÉNYLÉTHYLIDÈNE)BENZOHYDRAZIDE SUBSTITUÉS EN TANT QU'INHIBITEURS DE L'HISTONE DÉMÉTHYLASE
  申请人：UNIV UTAH RES FOUND

  公开号：WO2013025805A1

  公开（公告）日：2013-02-21

  In one aspect, the invention relates to substituted (E)-N'-(1- phenylethylidene)benzohydrazide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of lysine-specific histone demethylase, including LSD1; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the LSD1. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及替代(E)-N'-(1-苯乙烯基)苯甲酰肼类似物，其衍生物以及相关化合物，这些化合物可用作赖氨酸特异性组蛋白去甲基化酶的抑制剂，包括LSD1；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与LSD1功能障碍相关的疾病的方法。本摘要旨在作为在特定领域进行搜索的扫描工具，并不旨在限制本发明。
• SUBSTITUTED (E)-N'-(1-PHENYLETHYLIDENE)BENZOHYDRAZIDE ANALOGS AS HISTONE DEMETHYLASE INHIBITORS
  申请人：Vankayalapati Hariprasad

  公开号：US20140163017A1

  公开（公告）日：2014-06-12

  In one aspect, the invention relates to substituted (E)-N′-(1-phenylethylidene)benzohydrazide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of lysine-specific histone demethylase, including LSD1; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the LSD1. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，本发明涉及取代的(E)-N′-(1-苯乙烯基)苯肼类似物、其衍生物和相关化合物，它们可用作赖氨酸特异性组蛋白去甲基化酶，包括LSD1的抑制剂；制备这些化合物的合成方法；含有这些化合物的制药组合物；以及使用这些化合物和组合物治疗与LSD1功能障碍相关的疾病的方法。本摘要旨在作为搜索特定技术领域的扫描工具，不旨在限制本发明。
• SUBSTITUTED (E)-N'-(1-PHENYLETHYLIDENE) BENZOHYDRAZIDE ANALOGS AS HISTONE DEMETHYLASE INHIITORS
  申请人：University of Utah Research Foundation

  公开号：EP2744330B1

  公开（公告）日：2020-07-15
• SUBSTITUTED (3-(5-CHLORO-2-HYDROXYPHENYL)-1-BENZOYL-1H-PYRAZOLE COMPOUNDS AS HISTONE DEMETHYLASE INHIBITORS
  申请人：University of Utah Research Foundation

  公开号：EP3010915B1

  公开（公告）日：2019-05-08
• METHODS AND COMPOSITIONS OF TARGETED DRUG DEVELOPMENT
  申请人：Errico Peter Joseph

  公开号：US20080015194A1

  公开（公告）日：2008-01-17

  The present invention is directed to methods for developing one or more drugs for one or more targeted therapies and compositions derived therefrom. In accordance with one aspect of the present invention, combinatorial chemistry techniques for use with high throughput screening techniques for identifying small molecule affinity and/or activity interactions are avoided by instead utilizing the natural mechanisms of antigen response to effect a massively parallel screening of naturally occurring molecules against an antigen. Other aspects of the invention provide compositions derived therefrom as well as therapeutic methods of use for the compounds.