3-[2-(N,N-diethyl-N-methyl-ammonium)ethyl]-7-hydroxy-4-methylcoumarin | 327594-36-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 3-[2-(N,N-diethyl-N-methyl-ammonium)ethyl]-7-hydroxy-4-methylcoumarin
• 英文别名: AHMC；Diethyl-[2-(7-hydroxy-4-methyl-2-oxochromen-3-yl)ethyl]-methylazanium；diethyl-[2-(7-hydroxy-4-methyl-2-oxochromen-3-yl)ethyl]-methylazanium
• CAS: 327594-36-5
• 化学式: C₁₇H₂₄NO₃
• 分子量: 290.382
• InChiKey: JGXGFWUTRXWEJX-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

AMHC（3-[2-(N,N-二乙基-N-甲基铵)乙基]-7-羟基-4-甲基香豆素）是已知的人类代谢物，属于schembl237672。

AMHC (3-[2-(N,N-diethyl-Nmethylammonium)ethyl]-7-hydroxy-4-methylcoumarin) is a known human metabolite of schembl237672.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  AMMC 在 glucose-6-phosphate dehydrogenase 、 β-nicotinamide adenine dinucleotide phosphate disodium salt 、 recombinant human CYP₂D₆ enzyme 、 glucose-6-phosphate barium salt 作用下， 以 aq. phosphate buffer 为溶剂， 生成 3-[2-(N,N-diethyl-N-methyl-ammonium)ethyl]-7-hydroxy-4-methylcoumarin
  参考文献：
  名称：

  使用两种不同的底物，多酚及其结肠代谢产物对CYP2D6酶的抑制作用。

  摘要：

  多酚化合物（包括类黄酮，查耳酮，酚酸和呋喃香豆素）是我们饮食中的常见部分，但也是几种膳食补充剂和/或药物的有效成分。这些化合物通过人类生物转化酶和结肠的微生物区系进行广泛的代谢。CYP2D6酶代谢约25％的药物，其中一些药物的治疗窗口狭窄。因此，其抑制作用可导致药代动力学相互作用的发展和药物治疗的中断。在这项研究中，采用两种试验，使用不同的试验底物，检测了17种植物来源的化合物和19种结肠类黄酮代谢产物对CYP2D6的抑制作用。该Ø使用CypExpress 2D6试剂盒结合HPLC分析测试了右美沙芬的甲基化程度; 而另一种CYP2D6特异性底物（AMMC）的O-脱甲基作用则是通过BioVision Fluorometric CYP2D6试剂盒的酶标仪进行的。有趣的是，某些化合物（例如佛手柑）可同时抑制右美沙芬和AMMC的去甲基作用。但是，某些物质仅在其中一种测定方法中被证明是抑制剂。我们的

  DOI：

  10.1016/j.biopha.2020.110732

文献信息

• Cannabidiol, a Major Phytocannabinoid, As a Potent Atypical Inhibitor for CYP2D6
  作者：Satoshi Yamaori、Yasuka Okamoto、Ikuo Yamamoto、Kazuhito Watanabe

  DOI：10.1124/dmd.111.041384

  日期：2011.11

  Δ9-Tetrahydrocannabinol, cannabidiol (CBD), and cannabinol are the three major cannabinoids contained in marijuana, which are devoid of nitrogen atoms in their structures. In this study, we investigated the inhibitory effects of the major phytocannabinoids on the catalytic activity of human CYP2D6. These major cannabinoids inhibited the 3-[2-( N , N -diethyl- N -methylammonium)ethyl]-7-methoxy-4-methylcoumarin (AMMC) and dextromethorphan O -demethylase activities of recombinant CYP2D6 and pooled human liver microsomes in a concentration-dependent manner (IC50 = 4.01–24.9 μM), indicating the strongest inhibitory potency of CBD. However, these cannabinoids showed no or weak metabolism-dependent inhibition. CBD competitively inhibited the CYP2D6 activities with the apparent K i values of 1.16 to 2.69 μM. To clarify the structural requirement for CBD-mediated CYP2D6 inhibition, effects of CBD-related compounds on the AMMC O -demethylase activity of recombinant CYP2D6 were examined. Olivetol (IC50 = 7.21 μM) inhibited CYP2D6 activity as potently as CBD did (IC50 = 6.52 μM), whereas d -limonene did not show any inhibitory effect. Pentylbenzene failed to inhibit CYP2D6 activity. Furthermore, neither monomethyl nor dimethyl ethers of CBD inhibited the activity. Cannabidivarin having a propyl side chain inhibited CYP2D6 activity; its inhibitory effect (IC50 = 10.2 μM) was less potent than that of CBD. On the other hand, orcinol and resorcinol showed lack of inhibition. The inhibitory effect of CBD on CYP2D6 activity was more potent than those of 16 compounds without nitrogen atoms tested, such as progesterone. These results indicated that CBD caused potent direct CYP2D6 inhibition, in which two phenolic hydroxyl groups and the pentyl side chain of CBD may play important roles.

  Δ9-四氢大麻酚、大麻二酚（CBD）和大麻酚是大麻中含有的三种主要大麻素，其结构中不含氮原子。在这项研究中，我们研究了主要植物大麻素对人类 CYP2D6 催化活性的抑制作用。这些主要大麻素抑制重组 CYP2D6 的 3-[2-( N , N -二乙基 - N -甲基铵)乙基]-7-甲氧基-4-甲基香豆素 (AMMC) 和右美沙芬 O - 去甲基酶活性，并在一个实验中汇集人肝微粒体。浓度依赖性方式（IC50 = 4.01–24.9 μM），表明 CBD 的抑制效力最强。然而，这些大麻素没有表现出或表现出弱的代谢依赖性抑制。 CBD 竞争性抑制 CYP2D6 活性，表观 K i 值为 1.16 至 2.69 μM。为了阐明 CBD 介导的 CYP2D6 抑制的结构要求，检查了 CBD 相关化合物对重组 CYP2D6 的 AMMC O-去甲基酶活性的影响。 Olivetol (IC50 = 7.21 μM) 与 CBD (IC50 = 6.52 μM) 一样有效地抑制 CYP2D6 活性，而 d-柠檬烯没有表现出任何抑制作用。戊苯未能抑制 CYP2D6 活性。此外，CBD的单甲基醚和二甲醚均不抑制该活性。具有丙基侧链的大麻二酚抑制 CYP2D6 活性；其抑制作用（IC50 = 10.2 μM）不如 CBD 有效。另一方面，苔黑酚和间苯二酚表现出缺乏抑制作用。 CBD 对 CYP2D6 活性的抑制作用比测试的 16 种不含氮原子的化合物（例如黄体酮）更有效。这些结果表明 CBD 引起有效的直接 CYP2D6 抑制，其中两个酚羟基和 CBD 的戊基侧链可能发挥重要作用。
• Systems and Methods for Evaluating Enzyme Competency
  申请人：Melker Richard J.

  公开号：US20090005270A1

  公开（公告）日：2009-01-01

  The present invention provides systems and methods for determining enzymatic competency, which is important in determining whether a patient may suffer an adverse drug reaction, has a disease associated with defects in specific enzymatic function, and/or has an enzyme defect that is likely to cause pathophysiology. As contemplated herein, a parent molecular entity is administered to a patient in whom enzymatic competency is to be determined. A sample of the patient's bodily fluid is exposed to a sensor of the invention to distinguish, detect, and quantify a detectable entity in the bodily fluid. Sensor-acquired data regarding the detectable entity is used to determine enzymatic competency. Preferably, a sample of a patient's exhaled breath is collected and exposed to the sensor of the invention. Types of sensor systems of the invention include, but are not limited to, surface resonance arrays; microelectromechanical sensors (such as microcantilever-based technology); molecularly imprinted polymer sensors; amplifying fluorescent sensor technology; aptamer-based sensor technology; SAW sensors; infrared sensors; fuel cells; chemical reactors; and pH sensitive sensors.

  本发明提供了确定酶的能力的系统和方法，这对于确定患者是否可能遭受不良药物反应、是否患有与特定酶功能缺陷有关的疾病以及是否存在可能导致病理生理学的酶缺陷非常重要。如本文所述，将一种母分子实体注入到需要确定酶能力的患者体内。将患者体液样品暴露于本发明的传感器上，以区分、检测和量化体液中的可检测实体。使用传感器获取的有关可检测实体的数据来确定酶的能力。最好收集患者呼出的气息样品并将其暴露于本发明的传感器上。本发明的传感器系统类型包括但不限于表面共振阵列、微电子机械传感器（如基于微悬臂臂技术）、分子印迹聚合物传感器、放大荧光传感器技术、适配体传感器技术、SAW传感器、红外传感器、燃料电池、化学反应器和pH敏感传感器。
• Method to inhibit ischemia and reperfusion injury
  申请人：Gottlieb, Roberta

  公开号：EP2011489A2

  公开（公告）日：2009-01-07

  Methods of treating or inhibiting ischemia and reperfusion injury are provided.

  提供了治疗或抑制缺血和再灌注损伤的方法。
• Effects of artemisinin antimalarials on Cytochrome P450 enzymes<i>in vitro</i>using recombinant enzymes and human liver microsomes: potential implications for combination therapies
  作者：Therese Ericsson、Jesper Sundell、Angelica Torkelsson、Kurt-Jürgen Hoffmann、Michael Ashton

  DOI：10.3109/00498254.2013.878815

  日期：2014.7

  1. Cytochrome P450 enzyme system is the most important contributor to oxidative metabolism of drugs. Modification, and more specifically inhibition, of this system is an important determinant of several drug-drug interactions (DDIs).2. Effects of the antimalarial agent artemisinin and its structural analogues, artemether, artesunate and dihydroartemisinin, on seven of the major human liver CYP isoforms (CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6 and 3A4) were evaluated using recombinant enzymes (fluorometric assay) and human liver microsomes (LC-MS/MS analysis). Inhibitory potency (IC50) and mechanisms of inhibition were evaluated using nonlinear regression analysis. In vitro-in vivo extrapolation using the [I]/K-i ratio was applied to predict the risk of DDI in vivo.3. All compounds tested inhibited the enzymatic activity of CYPs, mostly through a mixed type of inhibition, with CYP1A2, 2B6, 2C19 and 3A4 being affected. A high risk of interaction in vivo was predicted if artemisinin is coadministrated with CYP1A2 or 2C19 substrates.4. With respect to CYP1A2 inhibition in vivo by artemisinin compounds, our findings are in line with previously published data. However, reported risks of interaction may be overpredicted and should be interpreted with caution.
• NOVEL CYP2D FLUORESCENT ASSAY REAGENTS
  申请人：GENTEST CORPORATION

  公开号：EP1095032A1

  公开（公告）日：2001-05-02