3'-羟基双氯芬酸 | 69002-85-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3'-羟基双氯芬酸
• 英文名称: 3'-Hydroxydiclofenac
• 英文别名: 4'-hydroxydiclofenac；2-[2-(2,6-dichloro-3-hydroxyanilino)phenyl]acetic acid
• CAS: 69002-85-3
• 化学式: C₁₄H₁₁Cl₂NO₃
• 分子量: 312.152
• InChiKey: HYPJZSYXUWYJDG-UHFFFAOYSA-N

物化性质

• 熔点：
  159-162 °C
• 沸点：
  429.5±45.0 °C(Predicted)
• 密度：
  1.520±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  4

ADMET

代谢

3p-羟基双氯芬酸已知的人体代谢物包括2-[2-(2,6-二氯-3-磺酸氧基苯基)苯基]乙酸和(2S,3S,4S,5R)-6-[3-[2-(羧甲基)苯胺基]-2,4-二氯苯氧基]-3,4,5-三羟基氧杂环己烷-2-羧酸。

3p-Hydroxy-diclofenac has known human metabolites that include 2-[2-(2,6-dichloro-3-sulfooxyanilino)phenyl]acetic acid and (2S,3S,4S,5R)-6-[3-[2-(carboxymethyl)anilino]-2,4-dichlorophenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  双氯芬酸 在 glucose-6-phosphate dehydrogenase 、 glucose-6-phosphate 、 ferredoxin 8 、 ferredoxin-NADP⁺ reductase B 、 recombinant CYP₂₆₇B₁ from Sorangium cellulosum So ce56 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 3'-羟基双氯芬酸
  参考文献：
  名称：

  CYP267A1 and CYP267B1 from Sorangium cellulosum So ce56 are Highly Versatile Drug Metabolizers

  摘要：

  食品与药物管理局和国际协调会议的指导方针强调了药物代谢物在临床试验中的重要性。因此，无论是作为分析标准的潜在应用，还是所需的毒理学测试，生产代谢物的真实来源都是非常重要的。由于我们之前已经展示了来自土壤细菌 Sorangium cellulosum So ce56 的细胞色素 P450 具有良好的生物技术潜力，因此我们在此研究了 CYP267 家族及其在转化市售药物（包括非甾体抗炎药、抗肿瘤药和抗高血压药）中的应用。CYP267 家族，尤其是 CYP267B1，显示出了转化多种底物的有趣能力。我们建立了依赖底物的提取方案，还优化了体外实验和基于大肠杆菌的全细胞生物转化的反应条件。我们能够检测到 CYP267A1 对 22 种药物中 7 种药物的活性，以及 CYP267B1 对 22 种药物中 14 种药物的转化能力。在我们利用 CYP267B1 和表达自体氧化还原伙伴铁氧还蛋白 8 和铁氧还蛋白-NADP+还原酶 B 建立的全细胞系统中，我们观察到了中等到较高的转化率（产率高达 85%）。由于野生型 CYP267B1 具有转化多种底物的巨大潜力，因此为筛选更多底物提供了广阔的空间，这将引起人们对未来利用 S. cellulosum So ce56 的 CYP267B1 生物技术的进一步关注。

  DOI：

  10.1124/dmd.115.068486

文献信息

• Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways
  作者：Roque Bort、Katherine Macé、Alan Boobis、Marı́a-José Gómez-Lechón、Andrea Pfeifer、José Castell

  DOI：10.1016/s0006-2952(99)00167-7

  日期：1999.9

  study was to re-examine the human hepatic metabolism of diclofenac, with special focus on the generation of minor hydroxylated metabolites implicated in the idiosyncratic hepatotoxicity of the drug. Different experimental approaches were used: human hepatocytes, human microsomes, and engineered cells expressing single human CYP (cytochromes P450). Human hepatocytes formed 3'-hydroxy-, 4'-hydroxy-, 5-hydroxy-

  这项研究的目的是重新检查双氯芬酸的人肝代谢，特别关注与药物特异肝毒性有关的次要羟基化代谢产物的产生。使用了不同的实验方法：人肝细胞，人微粒体和表达单个人CYP（细胞色素P450）的工程细胞。人肝细胞形成了3'-羟基-，4'-羟基-，5-羟基-4'，5-二羟基和N，5-二羟基双氯芬酸，以及几种内酰胺。人肝微粒体形成4'-和5-羟基双氯芬酸的过程遵循Michaelis-Menten动力学（Km 9 +/- 1 microM; Vmax 432 +/- 15 pmol / min / mg和Km 43 +/- 5 microM;和Vmax分别为15.4 +/- 0.6 pmol / min / mg）。将5-羟基双氯芬酸与人肝微粒体温育后检测到次生代谢物，产生4'，5-二羟基双氯芬酸（Km 15 +/- 1 microM; Vmax 96 +/- 3 pmol / min / mg）和少量的N，
• Albumin-binding compounds that prevent nonenzymatic glycation and that may be used for treatment of glycation-related pathologies
  申请人：——

  公开号：US20010034359A1

  公开（公告）日：2001-10-25

  The present invention is directed to compositions that inhibit the nonenzymatic glycation of albumin, as well as methods of using compounds that inhibit albumin glycation for the treatment of glycation-related pathologies.

  本发明涉及抑制白蛋白非酶促糖基化的组合物，并使用抑制白蛋白糖基化的化合物治疗糖基化相关病理的方法。
• Evaluation of MTBH, a novel hesperetin derivative, on the activity of hepatic cytochrome P450 isoform in vitro and in vivo using a cocktail method by HPLC-MS/MS
  作者：Yan Qin、Haijun Dong、Jiayin Sun、Yilong Zhang、Jun Li、Tianci Zhang、Guanjun Chen、Sheng Wang、Shuai Song、Wei Wang、Yuru Fan、Jie Wang、Xiaohui Huang、Chenlin Shen

  DOI：10.1080/00498254.2021.2009934

  日期：2021.12.2

  7-trihydroxy-4′-methoxyflavanone (MTBH), a novel hesperidin derivative, has potential in the prevention of hepatic disease, however, its effects on cytochrome P450 isoforms (CYP450s) remains unexplored. The purpose was to investigate the effects of MTBH on the mRNA, protein levels, and activities of six CYP450s (1A2, 2C11/9, 2D2/6, 3A1/4, 2C13/19, and 2E1) in vitro and in vivo. 2. In vitro study, rat and human

  摘要 1. 8-亚甲基-叔丁胺-3',5,7-三羟基-4'-甲氧基黄烷酮（MTBH）是一种新型橙皮苷衍生物，具有预防肝病的潜力，但其对细胞色素P450亚型的影响（ CYP450s）仍未开发。目的是在体外和体内研究MTBH 对六种 CYP450（1A2、2C11/9、2D2/6、3A1/4、2C13/19 和 2E1）的 mRNA、蛋白质水平和活性的影响。 2.体外研究采用大鼠和人肝微粒体，通过探针药物阐明MTBH对6个CYP450s的抑制作用。在体内研究中，Sprague-Dawley 雄性大鼠用 MTBH（25、50 或 100 mg/kg，连续 28 天）、苯巴比妥（80 mg/kg，连续 12 天）或 0.5% CMC-Na 溶液（对照组）通过灌胃给药，然后分别通过实时荧光定量PCR、蛋白质印迹和探针药物孵育系统分析肝脏CYP450s的mRNA、蛋白水平和活性。 3.体外研究表明，M
• Synthesis and quantitative structure-activity relationships of diclofenac analogs
  作者：Peter Moser、Alfred Sallmann、Irmgard Wiesenberg

  DOI：10.1021/jm00171a008

  日期：1990.9

  The synthesis of a series of 2-anilinophenylacetic acids, close analogues of diclofenac, is described. These compounds were tested in two models used for evaluating the activity of nonsteroidal antiinflammatory drugs (NSAID's), inhibition of cyclooxygenase enzyme activity in vitro, and adjuvant-induced arthritis (AdA) in rats. Statistically significant correlations were found between the inhibitory activities of the compounds in these two models, indicating that cyclooxygenase inhibition seems to be the underlying mechanism for the antiinflammatory activity of these compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the crucial parameters for activity in both models were the lipophilicity and the angle of twist between the two phenyl rings. Optimal activities were associated with halogen or alkyl substituents in both ortho positions of the anilino ring. Compounds with OH groups in addition to two ortho substituents or compounds with only one or no ortho substituents were less active.
• Monooxygenation of aromatic compounds by dioxygen with bioinspired systems using non-heme iron catalysts and tetrahydropterins: comparison with other reducing agents and interesting regioselectivity favouring meta-hydroxylation
  作者：Delphine Mathieu、Jean François Bartoli、Pierrette Battioni、Daniel Mansuy

  DOI：10.1016/j.tet.2004.03.006

  日期：2004.4

  Monooxygenation of aromatic compounds by dioxygen in the presence of catalytic amounts of an iron(II) salt and tetrahydropterins as reducing agents occurs with a regioselectivity favouring meta-hydroxylation of arenes bearing an electron-donating substituent, such as anisole, phenetole, toluene, and ethylbenzene. Comparison of similar systems using various reducing agents showed that only tetrahydropterins and ascorbate led to such a major meta-hydroxylation. The tetrahydropterin- and ascorbate-dependent systems should be useful for the preparation of meta-hydroxylated metabolites of aromatic drugs, as shown here in the case of diclofenac. (C) 2004 Elsevier Ltd. All rights reserved.