2-methyl-2-((4-nitrophenyl)thio)propanoic acid | 58076-37-2

• 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: 2-methyl-2-((4-nitrophenyl)thio)propanoic acid
• 英文别名: α-(4-nitro-phenylsulfanyl)-isobutyric acid；α-(4-Nitro-phenylmercapto)-isobuttersaeure；2-Methyl-2-(4-nitrophenylsulfanyl)propanoic acid；2-methyl-2-(4-nitrophenyl)sulfanylpropanoic acid
• CAS: 58076-37-2
• 化学式: C₁₀H₁₁NO₄S
• 分子量: 241.268
• InChiKey: HILMHSGKLHGSCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methyl-2-((4-nitrophenyl)thio)propanoic acid 以64%的产率得到
  参考文献：
  名称：

  ANDREANI F.; ANDRISANO R.; ANDREANI A., FARMACO ED. SCI , 1975, 30, NO 10, 847-858

  摘要：

  DOI：
• 作为产物：
  描述：

  2-Methyl-2-(4-nitro-phenylsulfanyl)-propionic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以59 %的产率得到2-methyl-2-((4-nitrophenyl)thio)propanoic acid
  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

• Copper-Catalyzed Synthesis of Hindered Ethers from α-Bromo Carbonyl Compounds
  作者：Zhe Zhou、Nicole Erin Behnke、László Kürti

  DOI：10.1021/acs.orglett.8b02371

  日期：2018.9.7

  A catalytic method for the synthesis of sterically hindered ethers and thioethers from α-bromo carbonyl compounds and the corresponding nucleophiles using an inexpensive Cu(I) catalytic system is reported. This facile transformation takes place at ambient temperature and does not require the exclusion of air or moisture; thus, it is well-suited for the functionalization and derivatization of complex

  报道了一种使用廉价的 Cu(I) 催化体系从 α-溴代羰基化合物和相应的亲核试剂合成位阻醚和硫醚的催化方法。这种转变在环境温度下发生，不需要排除空气或湿气；因此，它非常适合复杂有机分子的功能化和衍生化。
• Synthesis, In Vitro, In Vivo and In Silico Antidiabetic Bioassays of 4-Nitro(thio)phenoxyisobutyric Acids Acting as Unexpected PPARγ Modulators: An In Combo Study
  作者：Blanca Colin-Lozano、Héctor Torres-Gomez、Sergio Hidalgo-Figueroa、Fabiola Chávez-Silva、Samuel Estrada-Soto、Julio Cesar Almanza-Pérez、Gabriel Navarrete-Vazquez

  DOI：10.3390/ph15010102

  日期：——

  Four isobutyric acids (two nitro and two acetamido derivatives) were prepared in two steps and characterized using spectral analysis. The mRNA concentrations of PPARγ and GLUT-4 (two proteins documented as key diabetes targets) were increased by 3T3-L1 adipocytes treated with compounds 1–4, but an absence of in vitro expression of PPARα was observed. Docking and molecular dynamics studies revealed the plausible interaction between the synthesized compounds and PPARγ. In vivo studies established that compounds 1–4 have antihyperglycemic modes of action associated with insulin sensitization. Nitrocompound 2 was the most promising of the series, being orally active, and one of multiple modes of action could be selective PPARγ modulation due to its extra anchoring with Gln-286. In conclusion, we demonstrated that nitrocompound 2 showed strong in vitro and in vivo effects and can be considered as an experimental antidiabetic candidate.

  四个异丁酸（两个硝基和两个乙酰胺衍生物）通过两步制备，并使用光谱分析进行表征。用化合物1-4处理的3T3-L1脂肪细胞的PPARγ和GLUT-4的mRNA浓度增加，但观察到PPARα在体外表达的缺失。对接和分子动力学研究揭示了合成化合物与PPARγ之间的可能相互作用。体内研究表明，化合物1-4具有与胰岛素敏感性相关的抗高血糖作用。硝基化合物2是该系列中最有前途的，口服活性，可能的作用模式之一是选择性PPARγ调节，因为它与Gln-286有额外的锚定。总之，我们证明了硝基化合物2在体内和体外都表现出强烈的效果，可以被视为一种实验性抗糖尿病候选药物。
• <i>meta</i>‐C−H Arylation of Aniline Derivatives via Palladium/ S,O‐Ligand/Norbornene Cooperative Catalysis
  作者：Verena Sukowski、Manuela van Borselen、Simon Mathew、Bas de Bruin、M. Ángeles Fernández‐Ibáñez

  DOI：10.1002/anie.202317741

  日期：2024.1.25

  Aromatic amines are ubiquitous moieties in organic molecules and their direct functionalization is of great interest in many research areas due to their prevalence in pharmaceuticals and organic electronics. While several synthetic tools exist for the ortho‐ and para‐functionalization of anilines, the functionalization of the less reactive meta‐position is not easy to achieve with current methods. To date, the meta‐C−H arylation of aniline derivatives has been restricted to either the use of directing groups & templates, or their transformation into anilides & quaternary anilinium salts. Herein, we report the first general and efficient meta‐C−H‐arylation of non‐directed aniline derivatives via cooperative catalysis with a palladium–S,O‐ligand–norbornene system. The reaction proceeds under mild conditions with a wide range of aniline derivatives and aryl iodides, while being operationally simple and scalable. Our preliminary mechanistic investigation–including the isolation of several palladium complexes and deuterium experiments–reveal useful insights into the substituent‐effects of both the aniline‐substrate and the norbornene‐mediator during the meta‐C−H activation step.

  摘要 芳香胺是有机分子中无处不在的分子，由于芳香胺在医药和有机电子产品中的广泛应用，其直接官能化在许多研究领域都引起了极大的兴趣。虽然有多种合成工具可以实现苯胺的正官能化和对官能化，但目前的方法却难以实现反应性较低的元位的官能化。迄今为止，苯胺衍生物的元-C-H 芳基化仅限于使用定向基团和模板，或将其转化为苯胺类和季胺盐。在此，我们首次报道了通过钯-S,O-配体-降冰片烯体系的协同催化，对非定向苯胺衍生物进行通用而高效的元-C-H-芳基化反应。该反应在温和的条件下进行，适用于多种苯胺衍生物和芳基碘化物，同时操作简单、规模可控。我们的初步机理研究--包括分离几种钯配合物和氘实验--揭示了在元-C-H 活化步骤中苯胺底物和降冰片烯介质的取代效应。
• Galimberti; Defranceschi, Gazzetta Chimica Italiana, 1947, vol. 77, p. 431,435
  作者：Galimberti、Defranceschi

  DOI：——

  日期：——
• Andreani; Andrisano; Andreani, Farmaco, Edizione Scientifica, 1975, vol. 30, # 10, p. 847 - 858
  作者：Andreani、Andrisano、Andreani

  DOI：——

  日期：——