2-二乙氨基-2'-羟甲基-6'-甲基乙酰苯胺 | 64585-18-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 2-二乙氨基-2'-羟甲基-6'-甲基乙酰苯胺
• 中文别名: 利多卡因杂质6
• 英文名称: 2-diethylamino-2'-hydroxymethyl-6'-methyl acetanilide
• 英文别名: ω-Diethylamino-2-hydroxymethyl-6-methylacetanilid；2-(diethylamino)-N-[2-(hydroxymethyl)-6-methylphenyl]acetamide
• CAS: 64585-18-8
• 化学式: C₁₄H₂₂N₂O₂
• 分子量: 250.341
• InChiKey: JQMFXCNOZQVICE-UHFFFAOYSA-N

物化性质

• 沸点：
  417.2±45.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  利多卡因 在 ^3- disodium hydrogenphosphate 、 magnesium bis(monoperoxyphthalate)hexahydrate 、 柠檬酸 作用下， 反应 3.0h， 以26%的产率得到2-二乙氨基-2'-羟甲基-6'-甲基乙酰苯胺
  参考文献：
  名称：

  Carrier, M. N.; Battioni, P.; Mansuy, D., Bulletin de la Societe Chimique de France, 1993, vol. 130, # 3, p. 405 - 416

  摘要：

  DOI：

文献信息

• Quantification of Lidocaine and Several Metabolites Utilizing Chemical-Ionization Mass Spectrometry and Stable Isotope Labeling
  作者：S.D. Nelson、W.A. Garland、G.D. Breck、W.F. Trager

  DOI：10.1002/jps.2600660834

  日期：1977.8

  Quantification of the suspected metabolites of lidocaine in humans was carried out using the direct insertion probe and chemicalionization mass spectrometry. Deuterated analogs of the metabolites of lidocaine were added to serial human plasma and urine samples and were used as internal standards following oral administration of 250 mg of lidocaine hydrochloride monohydrate to two male subjects and

  使用直接插入探针和化学电离质谱法对可疑的利多卡因代谢产物进行定量。将利多卡因代谢物的氘代类似物添加至系列人血浆和尿液样本中，并在将250 mg盐酸利多卡因一水合物口服给予两名男性受试者和将202 mg利多卡因游离碱给予一名男性受试者后，用作内标。经过0-24小时尿液样品分析后的平均结果，在用β-葡萄糖醛酸苷酶-硫酸酯酶处理之前，表明存在以下量的7种可能的代谢产物（基于游离碱的给药剂量百分比）：利多卡因1.95 ; ω-乙基氨基-2,6-二甲基乙酰苯胺，4.90; ω-氨基-2,6-二甲基乙酰苯胺，0.88; 间羟基和/或对羟基利多卡因，0.73; 间和/或对羟基-ω-乙基氨基-2,6-二甲基乙酰苯胺，0.56; 2,6-二甲基苯胺，0.97; 和4-羟基-2，6-二甲基苯胺63.5。在人和恒河猴的尿液中均检测到N-乙基和N，N-二乙基甘氨酸，尽管未实现定量。
• Electrochemical Oxidation by Square-Wave Potential Pulses in the Imitation of Oxidative Drug Metabolism
  作者：Eslam Nouri-Nigjeh、Hjalmar P. Permentier、Rainer Bischoff、Andries P. Bruins

  DOI：10.1021/ac200897p

  日期：2011.7.15

  Electrochemistry combined with mass spectrometry (EC–MS) is an emerging analytical technique in the imitation of oxidative drug metabolism at the early stages of new drug development. Here, we present the benefits of electrochemical oxidation by square-wave potential pulses for the oxidation of lidocaine, a test drug compound, on a platinum electrode. Lidocaine was oxidized at constant potential and by square-wave potential pulses with different cycle times, and the reaction products were analyzed by liquid chromatography–mass spectrometry [LC–MS(/MS)]. Application of constant potentials of up to +5.0 V resulted in relatively low yields of N-dealkylation and 4-hydroxylation products, while oxidation by square-wave potential pulses generated up to 50 times more of the 4-hydroxylation product at cycle times between 0.2 and 12 s (estimated yield of 10%). The highest yield of the N-dealkylation product was obtained at cycle times shorter than 0.2 s. Tuning of the cycle time is thus an important parameter to modulate the selectivity of electrochemical oxidation reactions. The N-oxidation product was only obtained by electrochemical oxidation under air atmosphere due to reaction with electrogenerated hydrogen peroxide. Square-wave potential pulses may also be applicable to modulate the selectivity of electrochemical reactions with other drug compounds in order to generate oxidation products with greater selectivity and higher yield based on the optimization of cycle times and potentials. This considerably widens the scope of direct electrochemistry-based oxidation reactions for the imitation of in vivo oxidative drug metabolism.

  电化学结合质谱法（EC-MS）是一种新兴的分析技术，用于在新药开发的早期阶段模拟药物的氧化代谢。在此，我们介绍了方波电位脉冲电化学氧化法在铂电极上氧化利多卡因（一种测试药物化合物）的优势。利多卡因在恒定电位和不同周期时间的方波电位脉冲下被氧化，反应产物通过液相色谱-质谱法[LC-MS(/MS)]进行分析。使用高达 +5.0 V 的恒定电位时，N-脱烷基化和 4-羟基化产物的产率相对较低，而使用方波电位脉冲进行氧化时，在 0.2 至 12 秒的周期时间内，4-羟基化产物的产率最高可达 50 倍（估计产率为 10%）。因此，调整周期时间是调节电化学氧化反应选择性的一个重要参数。由于与电生过氧化氢发生反应，只有在空气环境下进行电化学氧化才能获得 N-氧化产物。方波电位脉冲也可用于调节其他药物化合物电化学反应的选择性，以便在优化循环时间和电位的基础上生成选择性更强、产率更高的氧化产物。这大大拓宽了基于电化学的直接氧化反应的范围，可用于模仿体内药物的氧化代谢。
• Carrier, M. N.; Battioni, P.; Mansuy, D., Bulletin de la Societe Chimique de France, 1993, vol. 130, # 3, p. 405 - 416
  作者：Carrier, M. N.、Battioni, P.、Mansuy, D.

  DOI：——

  日期：——