1-Naphthyl glucuronide | 17238-47-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-Naphthyl glucuronide
• 英文别名: 1-naphthol-glucuronide；O¹-[1]naphthyl-glucopyranuronic acid；O¹-[1]Naphthyl-glucopyranuronsaeure；Naphthyl glucuronide；(2S,3S,4S,5R)-3,4,5-trihydroxy-6-naphthalen-1-yloxyoxane-2-carboxylic acid
• CAS: 17238-47-0
• 化学式: C₁₆H₁₆O₇
• 分子量: 320.299
• InChiKey: KEQWBZWOGRCILF-AKFOCJAPSA-N

物化性质

• 熔点：
  100-106°C
• 沸点：
  623.0±55.0 °C(Predicted)
• 密度：
  1.567±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-Naphthyl glucuronide 、 alkaline earth salt of/the/ methylsulfuric acid 生成 萘酚 、 D-葡萄糖醛酸
  参考文献：
  名称：

  血管紧张素受体阻滞剂：保护靶器官的证据。

  摘要：

  高血压是整个发达国家的一个主要问题。尽管目前的抗高血压治疗方案可降低发病率和死亡率，但患者往往不依从，并且药物可能无法完全使血压正常化。因此，当前的治疗常常不能预防或逆转血压长期升高时经常发生的心血管重塑。阻断肾素-血管紧张素系统（RAS）可有效控制高血压和治疗充血性心力衰竭。血管紧张素转换酶 (ACE) 抑制剂和血管紧张素受体阻滞剂 (ARB) 都会抑制 RAS 的活性，但这两类抗高血压药物具有不同的作用机制和不同的药理学特征。血管紧张素转换酶抑制剂阻断血管紧张素 II (Ang II) 产生的单一途径。此外，血管紧张素I并不是ACE的唯一底物。ACE 抑制剂还可以阻止缓激肽的降解，这可能对心血管疾病有潜在的益处。然而，缓激肽是与 ACE 抑制剂治疗相关的咳嗽的推测原因。ACE 抑制剂临床试验的数据支持 RAS 参与心血管疾病的发展。血管紧张素受体阻滞剂作用于 RAS 远端，选择性阻断 Ang

  DOI：

  10.1002/clc.4960240303
• 作为产物：
  描述：

  萘酚 、 UDP-glucuronic acid 在 human UDP-glucuronosyltransferase 1A₉ 、 magnesium chloride 、 alamethicin 、 糖质酸-1,4-内酯 作用下， 生成 1-Naphthyl glucuronide
  参考文献：
  名称：

  Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches

  摘要：

  通过实验使用145种酚类化合物，并通过3D-QSAR方法分析，确定了人UGT1A9的催化选择性。UGT1A9是一种重要的膜结合酶，催化外源性物质的葡糖醛酸化反应。通过动力学分析确定了UGT1A9的催化效率。使用CoMFA和CoMSIA技术分析了定量结构活性关系。通过将葡糖醛酸化位点及其相邻的芳香环重叠，实现了底物结构的最大立体重叠。对于具有多个活性葡糖醛酸化位点的底物，每个位点被视为单独的底物。3D-QSAR分析产生了统计上可靠的模型，具有良好的预测能力（CoMFA：q2=0.548，r2=0.949，r pred 2=0.775；CoMSIA：q2=0.579，r2=0.876，r pred 2=0.700）。通过轮廓系数图阐明了底物中负责选择性差异的结构特征。将轮廓系数图叠加在UGT1A9的同源模型的催化口袋中，能够高度自信地识别UGT1A9的催化口袋。CoMFA/CoMSIA模型可以预测底物的选择性和UGT1A9的体外清除率。我们的发现还提供了理解UGT1A9功能和底物选择性的可能分子基础。

  DOI：

  10.1007/s11095-012-0666-z

文献信息

• NOVEL IMMORTALIZED HEPATIC CELL LINE ORIGINATING IN HUMANS
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1083223A1

  公开（公告）日：2001-03-14

  The present invention relates to a new immortalized hepatocyte culture of human (preferably human fetal) normal cell origin, a method of producing said culture, a screening method for a compound or a salt thereof which inhibits or promotes an enzyme activity involved in the metabolism of xenobiotics in the liver, or which inhibits or promotes the expression of a gene encoding an enzyme involved in the metabolism of xenobiotics in the liver, or which inhibits or promotes the induction of expression of a gene encoding an enzyme involved in the metabolism of xenobiotics in the liver, characterized by the use of said culture, a compound which inhibits or promotes an enzyme activity involved in the metabolism of xenobiotics in the liver, a compound which inhibits or promotes the expression of a gene encoding an enzyme involved in the metabolism of xenobiotics in the liver, or a compound which inhibits or promotes the induction of expression of a gene encoding an enzyme involved in the metabolism of xenobiotics in the liver, obtained using said screening method, or salts thereof. The immortalized hepatocyte culture of human normal cell origin of the present invention is useful in, for example, screening for compounds or salts thereof having therapeutic/preventive effects on hepatic insufficiency .

  本发明涉及一种新的人类（最好是人类胎儿）正常细胞来源的永生化肝细胞培养物，一种生产所述培养物的方法，一种筛选化合物或其盐的方法，该化合物或其盐可抑制或促进参与肝脏中异种生物代谢的酶活性，或可抑制或促进编码参与肝脏中异种生物代谢的酶的基因的表达，或可抑制或促进编码参与肝脏中异种生物代谢的酶的基因的诱导表达、或抑制或促进编码肝脏中参与异种生物代谢的酶的基因的表达，或抑制或促进编码肝脏中参与异种生物代谢的酶的基因的诱导表达、其特征在于使用所述培养物、使用所述筛选方法获得的抑制或促进参与肝脏中异 生素代谢的酶活性的化合物、抑制或促进参与肝脏中异生素代谢的酶编码基因表达的复 合物、或抑制或促进参与肝脏中异生素代谢的酶编码基因诱导表达的化合物或其盐。 本发明的人类正常细胞来源的永生化肝细胞培养物可用于例如筛选对肝功能不全具有治疗/预防作用的化合物或其盐类。
• Methods and compositions for extending lifespan
  申请人：Longevica Therapeutics Inc.

  公开号：US10653715B2

  公开（公告）日：2020-05-19

  The present invention relates to methods for attenuating aging, of health maintenance, and/or treating, or delaying the onset of, an age-related condition or disorder, in a subject comprising administering to the subject an effective amount of (a) one or more compounds that sustain pharmacological activation of xenobiotic metabolism or induce fermentation by gut bacteria to produce substances that activate xenobiotic metabolism enzymes and/or stimulate xenobiotic excretion and (b) one or more chelators. A further aspect of the invention is a composition comprising (a) and (b).

  本发明涉及减轻受试者衰老、维持健康和/或治疗与年龄有关的疾病或紊乱或推迟其发生的方法，包括向受试者施用有效量的(a)一种或多种化合物，这些化合物可持续药理激活异生物代谢或诱导肠道细菌发酵以产生激活异生物代谢酶和/或刺激异生物排泄的物质；以及(b)一种或多种螯合剂。本发明的另一方面是一种包含(a)和(b)的组合物。
• PROCESS FOR GLUCURONIDATION SCREENING
  申请人：——

  公开号：US20020076740A1

  公开（公告）日：2002-06-20

  A fluorescence polarization process used to identify activity of conjugative enzymes involved in xenobiotic transformations, such as glucuronosyltransferases.

  一种荧光偏振过程，用于识别参与异生物转化的共轭酶（如葡萄糖醛酸转移酶）的活性。
• Process for glucuronidation screening
  申请人：Invitrogen Corporation, a Delaware corporation

  公开号：US20040142410A1

  公开（公告）日：2004-07-22

  A fluorescence polarization process used to identify activity of conjugative enzymes involved in xenobiotic transformations, such as glucuronosyltransferases is provided.

  提供了一种荧光偏振过程，用于识别参与异生物转化的共轭酶（如葡萄糖醛酸转移酶）的活性。
• Phenylalanine 93 of the human UGT1A10 plays a major role in the interactions of the enzyme with estrogens
  作者：Camilla Höglund、Nina Sneitz、Anna Radominska-Pandya、Liisa Laakonen、Moshe Finel

  DOI：10.1016/j.steroids.2011.07.017

  日期：2011.12

  Little is currently known about the substrate binding site of the human UDP-glucuronosyltransferases (UGTs) and the structural elements that affect their complex substrate selectivity. In order to further understand and extend our earlier findings with phenylalanines 90 and 93 of UGT1A10, we have replaced each of them with Gly, Ala, Val, Leu, Ile or Tyr, and tested the activity of the resulting 12 mutants toward eight different substrates. Apart from scopoletin glucuronidation, the F90 mutants other than F90L were nearly inactive, while the F93 mutants' activity was strongly substrate dependent. Hence, F93L displayed high entacapone and 1-naphthol glucuronidation rates, whereas F93G, which was nearly inactive in entacapone glucuronidation, was highly active toward estradiol, estriol and even ethinylestradiol, a synthetic estrogen that is a poor substrate for the wild-type UGT1A10. Kinetic analyses of 4-nitrophenol, estradiol and ethinylestradiol glucuronidation by the mutants that catalyzed the respective reactions at considerable rates, revealed increased K-m, values for 4-nitrophenol and estradiol in all the mutants, whilst the K-m values of F93G and F93A for ethinylestradiol were lower than in control UGT1A10. Based on the activity results and a new molecular model of UGT1A10, it is suggested that both F90 and F93 are located in a surface helix at the far end of the substrate binding site. Nevertheless, only F93 directly affects the selectivity of UCT1A10 toward large and rigid estrogens, particularly those with substitutions at the D ring. The effects of F93 mutations on the glucuronidation of smaller or less rigid substrates are indirect, however. (C) 2011 Elsevier Inc. All rights reserved.