methyl 2-(hydroxy)formanilide-4-carboxylate | 876162-62-8

• 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: methyl 2-(hydroxy)formanilide-4-carboxylate
• 英文别名: 4-formylamino-3-hydroxy-benzoic acid methyl ester；4-Formamino-3-oxy-benzoesaeuremethylester；4-Formylamino-3-hydroxy-benzoesaeure-methylester；methyl 4-formamido-3-hydroxybenzoate
• CAS: 876162-62-8
• 化学式: C₉H₉NO₄
• 分子量: 195.175
• InChiKey: CEQZNFLHWCUANG-UHFFFAOYSA-N

物化性质

• 沸点：
  449.6±35.0 °C(Predicted)
• 密度：
  1.369±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(hydroxy)formanilide-4-carboxylate 生成 alkaline earth salt of/the/ methylsulfuric acid
  参考文献：
  名称：

  v. Meyer, Journal fur praktische Chemie (Leipzig 1954), 1915, vol. <2> 92, p. 265

  摘要：

  DOI：
• 作为产物：
  描述：

  4-氨基-3-羟基苯甲酸 在 硫酸 作用下， 以 水 为溶剂， 反应 48.0h， 生成 methyl 2-(hydroxy)formanilide-4-carboxylate
  参考文献：
  名称：

  鉴定邻羟基苯胺作为赖氨酸脱甲基酶5抑制剂的新型支架。

  摘要：

  Fe（II）/α-酮戊二酸依赖性赖氨酸脱甲基酶（KDMs）是多种疾病（包括癌症）的引人注目的药物靶标。在这项研究中，我们设计和筛选了有望用作Fe（II）螯合剂的邻位取代的酸酐，并确定了邻羟基苯胺作为KDM5A抑制剂的新型支架。用4-羧基-2-羟基甲酰苯胺（9c）的前药形式治疗人肺癌A549细胞时，组蛋白H3水平上的三甲基赖氨酸4含量增加，提示该细胞中存在KDM5抑制作用。

  DOI：

  10.1016/j.bmcl.2019.03.028

文献信息

• Structural Requirements for Factor Xa Inhibition by 3-Oxybenzamides with Neutral P1 Substituents:  Combining X-ray Crystallography, 3D-QSAR, and Tailored Scoring Functions
  作者：Hans Matter、David W. Will、Marc Nazaré,、Herman Schreuder、Volker Laux、Volkmar Wehner

  DOI：10.1021/jm049187l

  日期：2005.5.1

  The design, synthesis, and structure-activity relationship of 3-oxybenzamides as potent inhibitors of the coagulation protease factor Xa are described on the basis of X-ray structures, privileged structure motifs, and SAR information. A total of six X-ray structures of fXa/inhibitor complexes led us to identify the major protein-ligand interactions. The binding mode is characterized by a lipophilic dichlorophenyl substituent interacting with Tyr228 in the protease S1 pocket, while polar parts are accommodated in S4. This alignment in combination with docking allowed derivation of 3D-QSAR models and tailored scoring functions to rationalize biological affinity and provide guidelines for optimization. The resulting models showed good correlation coefficients and predictions of external test sets. Furthermore, they correspond to binding site topologies in terms of steric, electrostatic, and hydrophobic complementarity. Two approaches to derive tailored scoring functions combining binding site and ligand information led to predictive models with acceptable predictions of the external set. Good correlations to experimental affinities were obtained for both AFMoC (adaptation of fields for molecular comparison) and the novel TScore function. The SAR information from 3D-QSAR and tailored scoring functions agrees with all experimental data and provides guidelines and reasonable activity estimations for novel fXa inhibitors.
• Novel factor Xa inhibitors based on a benzoic acid scaffold and incorporating a neutral P1 ligand
  作者：Marc Nazaré、Hans Matter、Otmar Klingler、Fahad Al-Obeidi、Herman Schreuder、Gerhard Zoller、Jörg Czech、Martin Lorenz、Angela Dudda、Anusch Peyman、Hans Peter Nestler、Matthias Urmann、Armin Bauer、Volker Laux、Volkmar Wehner、David W. Will

  DOI：10.1016/j.bmcl.2004.03.059

  日期：2004.6

  A series of novel, highly potent, achiral factor Xa inhibitors based on a benzoic acid scaffold and containing a chlorophenethyl moiety directed towards the protease S1 pocket is described. A number of structural features, such as the requirements of the P1, P4 and ester-binding pocket ligands were explored with respect to inhibition of factor Xa. Compound 46 was found to be the most potent compound in a series of antithrombotic secondary assays. (C) 2004 Elsevier Ltd. All rights reserved.
• v. Meyer, Journal fur praktische Chemie (Leipzig 1954), 1915, vol. <2> 92, p. 265
  作者：v. Meyer

  DOI：——

  日期：——
• Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors
  作者：Pattaporn Jaikhan、Benjaporn Buranrat、Yukihiro Itoh、Jiranan Chotitumnavee、Takashi Kurohara、Takayoshi Suzuki

  DOI：10.1016/j.bmcl.2019.03.028

  日期：2019.5

  attractive drug targets for several diseases including cancer. In this study, we designed and screened ortho-substituted anilides that are expected to function as Fe(II) chelators, and identified ortho-hydroxy anilide as a novel scaffold for KDM5A inhibitors. Treatment of human lung cancer A549 cells with a prodrug form of 4-carboxy-2-hydroxy-formanilide (9c) increased trimethylated lysine 4 on histone

  Fe（II）/α-酮戊二酸依赖性赖氨酸脱甲基酶（KDMs）是多种疾病（包括癌症）的引人注目的药物靶标。在这项研究中，我们设计和筛选了有望用作Fe（II）螯合剂的邻位取代的酸酐，并确定了邻羟基苯胺作为KDM5A抑制剂的新型支架。用4-羧基-2-羟基甲酰苯胺（9c）的前药形式治疗人肺癌A549细胞时，组蛋白H3水平上的三甲基赖氨酸4含量增加，提示该细胞中存在KDM5抑制作用。