4-hydroxy-N’-[(E)-[4-dimethylaminophenyl]methylidene]benzohydrazide

• 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)-[4-dimethylaminophenyl]methylidene]benzohydrazide
• 英文别名: N'-{(E)-[4'-(dimethylamino)phenyl]methylidene}4hydroxylbenzohydrazide；N'-{(E)-[4-(dimethylamino)phenyl]methylidene}-4-hydroxybenzohydrazide；N-[(E)-[4-(dimethylamino)phenyl]methylideneamino]-4-hydroxybenzamide
• 化学式: C₁₆H₁₇N₃O₂
• 分子量: 283.33
• InChiKey: HZGBUEIBRGHLGQ-GZTJUZNOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  64.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-羟基苯甲酰肼 、 对二甲氨基苯甲醛 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以86%的产率得到4-hydroxy-N’-[(E)-[4-dimethylaminophenyl]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

• Thymidine phosphorylase and prostrate cancer cell proliferation inhibitory activities of synthetic 4-hydroxybenzohydrazides: In vitro, kinetic, and in silico studies
  作者：Sumaira Javaid、Syed Muhammad Saad、Humaira Zafar、Rizwana Malik、Khalid Mohammed Khan、M. Iqbal Choudhary、Atta-ur Rahman

  DOI：10.1371/journal.pone.0227549

  日期：——

  Over-expression of thymidine phosphorylase (TP) plays a key role in many pathological complications, including angiogenesis which leads to cancer cells proliferation. Thus in search of new anticancer agents, a series of 4-hydroxybenzohydrazides (1–29) was synthesized, and evaluated for in vitro thymidine phosphorylase inhibitory activity. Twenty compounds 1–3, 6–14, 16, 19, 22–24, and 27–29 showed potent to weak TP inhibitory activities with IC50 values in the range of 6.8 to 229.5 μM, in comparison to the standards i.e. tipiracil (IC50 = 0.014 ± 0.002 μM) and 7-deazaxanthine (IC50 = 41.0 ± 1.63 μM). Kinetic studies on selected inhibitors 3, 9, 14, 22, 27, and 29 revealed uncompetitive and non-competitive modes of inhibition. Molecular docking studies of these inhibitors indicated that they were able to interact with the amino acid residues present in allosteric site of TP, including Asp391, Arg388, and Leu389. Antiproliferative (cytotoxic) activities of active compounds were also evaluated against mouse fibroblast (3T3) and prostate cancer (PC3) cell lines. Compounds 1, 2, 19, and 22–24 exhibited anti-proliferative activities against PC3 cells with IC50 values between 6.5 to 10.5 μM, while they were largely non-cytotoxic to 3T3 (mouse fibroblast) cells proliferation. Present study thus identifies a new class of dual inhibitors of TP and cancer cell proliferation, which deserves to be further investigated for anti-cancer drug development.

  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。
• Persistent photoconductive coating composition
  申请人：Polychrome Corporation

  公开号：EP0385376A2

  公开（公告）日：1990-09-05

  A persistent photoconductive coating composition contains a persistent photoconductor, photoinitiator and an acetate or phenolic hydroxyl-containing resin dispersed in an inert coherent matrix.

  一种持久性光电导涂层组合物包含一种持久性光电导体、光引发剂和一种分散在惰性相干基质中的醋酸或含酚羟基树脂。
• MODULATORS OF HEDGEHOG SIGNALING PATHWAY
  申请人：PRESIDENT AND FELLOW OF HARVARD COLLEGE

  公开号：US20130274233A1

  公开（公告）日：2013-10-17

  The invention provides compounds and methods for modulating the Hedgehog signaling pathway. The compounds modulate the translocation and/or accumulation of smoothened to the primary cilia.
• 4-HYDROXYBENZOHYDARZIDE-A NEW CLASS OF ANGIOGENIC ENZYME THYMIDINE PHOSPHORYLASE INHIBITORS
  申请人：Choudhary Muhammad Iqbal

  公开号：US20170246130A1

  公开（公告）日：2017-08-31

  The present invention relates to anti-thymidine phosphorylase compounds. These compounds are derivatives of 4-hydroxybenzohydarzide or generally Schiff bases of hydrazones. The invention evaluates a series of Schiff bases of hydrazones against thymidine phosphorylase, and identified significant inhibitors of thymidine phosphorylase enzyme during in vitro studies.
• US4960663A
  申请人：——

  公开号：US4960663A

  公开（公告）日：1990-10-02