4-hydroxy-N’-[(E)-(4-bromophenyl)methylidene]benzohydrazide | 1415703-68-2

• 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-bromophenyl)methylidene]benzohydrazide
• 英文别名: N'-[(E)-(4'-bromophenyl)methylidene]-4-hydroxylbenzohydrazide；(E)-N'-(4-bromobenzylidene)-4-hydroxybenzohydrazide；N'-(4-bromobenzylidene)-4-hydroxybenzohydrazide；N-[(E)-(4-bromophenyl)methylideneamino]-4-hydroxybenzamide
• CAS: 1415703-68-2
• 化学式: C₁₄H₁₁BrN₂O₂
• 分子量: 319.158
• InChiKey: NTCZEIJENYPNKE-CXUHLZMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 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：
  61.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-羟基苯甲酰肼 、 对溴苯甲醛 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以81.9%的产率得到4-hydroxy-N’-[(E)-(4-bromophenyl)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

• (<i>E</i>)-<i>N</i>′-(4-Chlorobenzylidene)-, (<i>E</i>)-<i>N</i>′-(4-bromobenzylidene)- and (<i>E</i>)-<i>N</i>′-[4-(diethylamino)benzylidene]- derivatives of 4-hydroxybenzohydrazide
  作者：Ashokkumar Subashini、Kandasamy Ramamurthi、Helen Stoeckli-Evans

  DOI：10.1107/s0108270112038462

  日期：2012.10.15

  The 4-chloro- [C₁₄H₁₁ClN₂O₂, (I)], 4-bromo- [C₁₄H₁₀BrN₂O₂, (II)] and 4-diethylamino- [C₁₈H₂₁N₃O₂, (III)] derivatives of benzylidene-4-hydroxybenzohydrazide, all crystallize in the same space group (P2₁/c), (I) and (II) also being isomorphous. In all three compounds, the conformation about the C=N bond isE. The molecules of (I) and (II) are relatively planar, with dihedral angles between the two benzene rings of 5.75 (12) and 9.81 (17)°, respectively. In (III), however, the same angle is 77.27 (9)°. In the crystal structures of (I) and (II), two-dimensional slab-like networks extending in theaandcdirections are formedviaN—H...O and O—H...O hydrogen bonds. The molecules stack head-to-tailviaπ–π interactions involving the aromatic rings [centroid–centroid distance = 3.7622 (14) Å in (I) and 3.8021 (19) Å in (II)]. In (III), undulating two-dimensional networks extending in thebandcdirections are formedviaN—H...O and O—H...O hydrogen bonds. The molecules stack head-to-headviaπ–π interactions involving inversion-related benzene rings [centroid–centroid distances = 3.6977 (12) and 3.8368 (11) Å].

  苄叉-4-羟基苯甲酰肼的 4-氯-[C14H11ClN2O2，(I)]、4-溴-[C14H10BrN2O2，(II)]和 4-二乙氨基-[C18H21N3O2，(III)]衍生物都在同一空间群（P21/c）中结晶，(I)和(II)也是同构的。在这三种化合物中，关于 C=N 键的构象均为 E。(I) 和 (II) 的分子相对平面，两个苯环之间的二面角分别为 5.75 (12) 和 9.81 (17)°。而在（III）中，同一角度为 77.27 (9)°。在 (I) 和 (II) 的晶体结构中，通过 N-H...O 和 O-H...O 氢键形成了沿 a 和 c 方向延伸的二维板状网络。分子通过涉及芳香环的π-π 相互作用从头到尾堆积起来[(I) 中的中心-中心距离 = 3.7622 (14) Å，(II) 中的中心-中心距离 = 3.8021 (19) Å]。在 (III) 中，通过 N-H...O 和 O-H...O 氢键形成了沿带方向延伸的波状二维网络。分子头对头通过涉及反转相关苯环的π-π 相互作用堆叠[中心-中心距离 = 3.6977 (12) 和 3.8368 (11) Å]。
• 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.
• 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。