2-(2-carboxyphenylthio)-N-(4-carboxyphenyl)acetamide | 884803-01-4

• 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: 2-(2-carboxyphenylthio)-N-(4-carboxyphenyl)acetamide
• 英文别名: 2-(2-carboxyphenylsulfanyl)-N-(4-carboxyphenyl)acetamide；2-{[2-(4-Carboxyanilino)-2-oxoethyl]sulfanyl}benzoic acid；2-[2-(4-carboxyanilino)-2-oxoethyl]sulfanylbenzoic acid
• CAS: 884803-01-4
• 化学式: C₁₆H₁₃NO₅S
• 分子量: 331.349
• InChiKey: NMTCFUNJEPOVRR-UHFFFAOYSA-N

物化性质

• 熔点：
  264 °C(Solv: ethanol (64-17-5))
• 沸点：
  632.9±50.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对氨基苯甲酸 在 sodium carbonate 、 potassium carbonate 作用下， 以 水 、 丙酮 、 乙腈 为溶剂， 反应 12.5h， 生成 2-(2-carboxyphenylthio)-N-(4-carboxyphenyl)acetamide
  参考文献：
  名称：

  Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit cancer growth

  摘要：

  针对人类胸苷酸合成酶（hTS）这种二聚酶的药物被广泛用于抗癌治疗。然而，使用传统的底物位点定向 TS 抑制剂治疗会诱导这种蛋白质的过度表达并产生耐药性。因此，我们另辟蹊径，发现了 TS 二聚体脱稳剂。这些化合物与单体-单体界面结合，使重组蛋白和细胞内蛋白的二聚化平衡向非活性单体转移。结构、光谱和动力学研究为这些小分子与 hTS 的相互作用效果提供了证据和定量信息。我们重点研究了其中的佼佼者 E7，结果表明它能抑制癌细胞中的 hTS，并加速其蛋白酶体降解，从而降低酶在细胞内的水平。在人类胰腺癌和卵巢癌小鼠模型中，E7 的抗癌效果也优于氟尿嘧啶。因此，在发现第一种TS原药抑制剂氟尿嘧啶六十多年后，E7打破了TS抑制与反应表达增强之间的联系，为抗击耐药性癌症提供了一种策略。

  DOI：

  10.7554/elife.73862

文献信息

• Synthesis and analgesic effects of 2-(2-carboxyphenylsulfanyl)-N-(4-substitutedphenyl)acetamide derivatives
  作者：Ümide Demir Özkay、Yusuf Özkay、Özgür Devrim Can

  DOI：10.1007/s00044-010-9300-y

  日期：2011.3

  This present study was undertaken to synthesize and investigate possible analgesic activities of some 2-(2-carboxyphenylsulfanyl)-N-(4-substitutedphenyl)acetamide derivatives that were designed by combining an analgesic drug thiosalicylic acid and the main pharmacophore group of paracetamol, N-(4-substitutedphenylacetamide). Chemical structures of synthesized compounds were elucidated by IR, H-1-NMR, and Mass spectral data. Paracetamol, thiosalicylic acid and some of the synthesized compounds in the series exhibited significant analgesic activities in hot-plate, tail-clip, and acetic acid-induced writhing tests. Compound 2d showed more potent analgesic activity than both paracetamol and thiosalicylic acid. None of the compounds changed the responses of animals recorded in Rota-Rod or activity cage tests with respect to control values. Therefore, analgesic activities of the synthesized compounds evaluated in this study were not caused by motor impairments or neurosedative effects.
• Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit cancer growth
  作者：Luca Costantino、Stefania Ferrari、Matteo Santucci、Outi MH Salo-Ahen、Emanuele Carosati、Silvia Franchini、Angela Lauriola、Cecilia Pozzi、Matteo Trande、Gaia Gozzi、Puneet Saxena、Giuseppe Cannazza、Lorena Losi、Daniela Cardinale、Alberto Venturelli、Antonio Quotadamo、Pasquale Linciano、Lorenzo Tagliazucchi、Maria Gaetana Moschella、Remo Guerrini、Salvatore Pacifico、Rosaria Luciani、Filippo Genovese、Stefan Henrich、Silvia Alboni、Nuno Santarem、Anabela da Silva Cordeiro、Elisa Giovannetti、Godefridus J Peters、Paolo Pinton、Alessandro Rimessi、Gabriele Cruciani、Robert M Stroud、Rebecca C Wade、Stefano Mangani、Gaetano Marverti、Domenico D'Arca、Glauco Ponterini、Maria Paola Costi

  DOI：10.7554/elife.73862

  日期：——

  Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces over-expression of this protein and development of drug resistance. We thus pursued an alternative strategy that led us to the discovery of TS-dimer destabilizers. These compounds bind at the monomer-monomer interface and shift the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers. A structural, spectroscopic, and kinetic investigation has provided evidence and quantitative information on the effects of the interaction of these small molecules with hTS. Focusing on the best among them, E7, we have shown that it inhibits hTS in cancer cells and accelerates its proteasomal degradation, thus causing a decrease in the enzyme intracellular level. E7 also showed a superior anticancer profile to fluorouracil in a mouse model of human pancreatic and ovarian cancer. Thus, over sixty years after the discovery of the first TS prodrug inhibitor, fluorouracil, E7 breaks the link between TS inhibition and enhanced expression in response, providing a strategy to fight drug-resistant cancers.

  针对人类胸苷酸合成酶（hTS）这种二聚酶的药物被广泛用于抗癌治疗。然而，使用传统的底物位点定向 TS 抑制剂治疗会诱导这种蛋白质的过度表达并产生耐药性。因此，我们另辟蹊径，发现了 TS 二聚体脱稳剂。这些化合物与单体-单体界面结合，使重组蛋白和细胞内蛋白的二聚化平衡向非活性单体转移。结构、光谱和动力学研究为这些小分子与 hTS 的相互作用效果提供了证据和定量信息。我们重点研究了其中的佼佼者 E7，结果表明它能抑制癌细胞中的 hTS，并加速其蛋白酶体降解，从而降低酶在细胞内的水平。在人类胰腺癌和卵巢癌小鼠模型中，E7 的抗癌效果也优于氟尿嘧啶。因此，在发现第一种TS原药抑制剂氟尿嘧啶六十多年后，E7打破了TS抑制与反应表达增强之间的联系，为抗击耐药性癌症提供了一种策略。