methoxyethyl etomidate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methoxyethyl etomidate
• 英文别名: 2-methoxyethyl 3-[(1R)-1-phenylethyl]imidazole-4-carboxylate
• 化学式: C₁₅H₁₈N₂O₃
• 分子量: 274.32
• InChiKey: JJSJTELMIQBHDE-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  53.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methoxyethyl etomidate 在 盐酸 作用下， 以 乙醚 为溶剂， 以1.97 g的产率得到2-methoxyethyl 3-[(1R)-1-phenylethyl]imidazole-4-carboxylate;hydrochloride
  参考文献：
  名称：

  N-Substituted Imidazole Carboxylic Ester Chiral Compound Containing an Ether Side Chain, Its Preparation and Application

  摘要：

  本发明涉及一种含有醚侧链的N-取代咪唑羧酸酯手性化合物及其制备和应用。该化合物的结构由公式（I）表示。该化合物可以引起迅速可逆的全身麻醉效果。动物实验表明，该化合物具有快速短效的药理特性，因此可以用作快速短效的全身麻醉药物。与依托咪酯相比，该化合物可以减少对肾上腺皮质激素合成的抑制作用，具有术后患者快速完全恢复的优势。该化合物结构中唯一的手性碳属于R型。该化合物结构中的咪唑环具有可酸化的N原子，因此该化合物或其相关的药学可接受的盐可用于制备中枢抑制药物，通过静脉或非静脉途径对动物或人类产生镇静、催眠和/或麻醉作用。

  公开号：

  US20170001963A1
• 作为产物：
  描述：

  依托咪酯 在 potassium carbonate 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 methoxyethyl etomidate
  参考文献：
  名称：

  Metabolite-inactive etomidate analogues alleviating suppression on adrenal function in Beagle dogs

  摘要：

  Owing to rapid generation in body, the metabolites of etomidate softdrug are able to accumulate in either the brain or periphery and subsequently affect the recovery from anaesthesia or cause corticosteroid suppression. This study was designed to investigate the ability of two etomidate analogues (ET-26, ET-42) with inactive metabolites to provide anaesthesia with lesser corticosteroid suppression. The 50% effective dose (ED50) of ET-26, ET-42, Etomidate, MOC-ET (an etomidate softdrug) and CPMM (an improved etomidate softdrug) required to induce anaesthesia intravenously in Beagle dogs were 1.44 mg/kg, 0.72 mg/kg, 0.43 mg/kg 23.12 mg/kg and 0.59 mg/kg, respectively. After adrenocorticotropic hormone (ACTH) stimulation, the serum concentrations of cortisol and corticosterone in the ET-26, ET-42 and CPMM groups were similar to those of controls, and significantly higher than those of the etomidate and MOC-etomidate groups (P < 0.05). Furthermore, no significant differences in serum concentrations of cortisol and corticosterone after ACTH-stimulation between ET-26, ET-42, CPMM, and blank control groups were observed. In this study, anaesthetic potencies of ET-26 (ED50 = 1.44 mg/kg) and ET-42 (ED50 = 0.72 mg/kg) were determined. Both analogues can significantly reduce the corticosteroid suppression in vivo. Metabolite-inactive etomidate derivatives with slow metabolism might provide a novel strategy to improve Etomidate associated corticosteroid suppression. (C) 2017 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2016.12.041

文献信息

• N-SUBSTITUTED IMIDAZOLE CARBOXYLIC ESTER CHIRAL COMPOUND CONTAINING ETHER SIDE CHAIN, PREPARATION METHOD AND APPLICATION
  申请人：West China Hospital, Sichuan University

  公开号：EP3088394A1

  公开（公告）日：2016-11-02

  The present invention relates to an N-substituted imidazole carboxylic ester chiral compound containing an ether side chain and to its preparation and application. The structure of this compound is represented by Formula (I). This compound can induce a rapid and reversible general anesthesia effect. Animal experiments show that this compound has rapid and short-acting pharmacological characteristics, so that it can be used as a rapid and short-acting general anesthesia medicine. Compared with etomidate, this compound can reduce the inhibition on the synthesis of adrenal cortical hormone, with an advantage of rapid and full recovery of the post-operative patient. The only chiral carbon in the compound structure belongs to the R form. This imidazole ring in the compound structure has acidifiable N atoms, so that this compound or its related pharmaceutically-acceptable salts can be used in preparation of the central inhibitory medicines, which can produce sedative, hypnotic and/or anesthetic effects on animals or human beings via their intravenous or non-intravenous administration.

  本发明涉及一种含有醚侧链的 N-取代咪唑羧酸酯手性化合物及其制备和应用。该化合物的结构由式（I）表示。该化合物可诱导快速、可逆的全身麻醉效果。动物实验表明，该化合物具有速效、短效的药理特性，可用作速效、短效全身麻醉药。与依托咪酯相比，该化合物能减少对肾上腺皮质激素合成的抑制，具有使术后病人迅速完全恢复的优点。该化合物结构中唯一的手性碳属于 R 形式。该化合物结构中的咪唑环具有可酸化的 N 原子，因此该化合物或其相关的药学上可接受的盐类可用于制备中枢抑制药物，通过静脉或非静脉给药对动物或人体产生镇静、催眠和/或麻醉作用。
• US9969695B2
  申请人：——

  公开号：US9969695B2

  公开（公告）日：2018-05-15
• N-Substituted Imidazole Carboxylic Ester Chiral Compound Containing an Ether Side Chain, Its Preparation and Application
  申请人：WEST CHINA HOSPITAL, SICHUAN UNIVERSITY

  公开号：US20170001963A1

  公开（公告）日：2017-01-05

  The present invention relates to an N-substituted imidazole carboxylic ester chiral compound containing an ether side chain and to its preparation and application. The structure of this compound is represented by Formula (I). This compound can induce a rapid and reversible general anesthesia effect. Animal experiments show that this compound has rapid and short-acting pharmacological characteristics, so that it can be used as a rapid and short-acting general anesthesia medicine. Compared with etomidate, this compound can reduce the inhibition on the synthesis of adrenal cortical hormone, with an advantage of rapid and full recovery of the post-operative patient. The only chiral carbon in the compound structure belongs to the R form. This imidazole ring in the compound structure has acidifiable N atoms, so that this compound or its related pharmaceutically-acceptable salts can be used in preparation of the central inhibitory medicines, which can produce sedative, hypnotic and/or anesthetic effects on animals or human beings via their intravenous or non-intravenous administration.

  本发明涉及一种含有醚侧链的N-取代咪唑羧酸酯手性化合物及其制备和应用。该化合物的结构由公式（I）表示。该化合物可以引起迅速可逆的全身麻醉效果。动物实验表明，该化合物具有快速短效的药理特性，因此可以用作快速短效的全身麻醉药物。与依托咪酯相比，该化合物可以减少对肾上腺皮质激素合成的抑制作用，具有术后患者快速完全恢复的优势。该化合物结构中唯一的手性碳属于R型。该化合物结构中的咪唑环具有可酸化的N原子，因此该化合物或其相关的药学可接受的盐可用于制备中枢抑制药物，通过静脉或非静脉途径对动物或人类产生镇静、催眠和/或麻醉作用。
• Metabolite-inactive etomidate analogues alleviating suppression on adrenal function in Beagle dogs
  作者：Jun Yang、Yi Kang、Bin Wang、Linghui Yang、Jin Liu、Wensheng Zhang

  DOI：10.1016/j.ejps.2016.12.041

  日期：2017.3

  Owing to rapid generation in body, the metabolites of etomidate softdrug are able to accumulate in either the brain or periphery and subsequently affect the recovery from anaesthesia or cause corticosteroid suppression. This study was designed to investigate the ability of two etomidate analogues (ET-26, ET-42) with inactive metabolites to provide anaesthesia with lesser corticosteroid suppression. The 50% effective dose (ED50) of ET-26, ET-42, Etomidate, MOC-ET (an etomidate softdrug) and CPMM (an improved etomidate softdrug) required to induce anaesthesia intravenously in Beagle dogs were 1.44 mg/kg, 0.72 mg/kg, 0.43 mg/kg 23.12 mg/kg and 0.59 mg/kg, respectively. After adrenocorticotropic hormone (ACTH) stimulation, the serum concentrations of cortisol and corticosterone in the ET-26, ET-42 and CPMM groups were similar to those of controls, and significantly higher than those of the etomidate and MOC-etomidate groups (P < 0.05). Furthermore, no significant differences in serum concentrations of cortisol and corticosterone after ACTH-stimulation between ET-26, ET-42, CPMM, and blank control groups were observed. In this study, anaesthetic potencies of ET-26 (ED50 = 1.44 mg/kg) and ET-42 (ED50 = 0.72 mg/kg) were determined. Both analogues can significantly reduce the corticosteroid suppression in vivo. Metabolite-inactive etomidate derivatives with slow metabolism might provide a novel strategy to improve Etomidate associated corticosteroid suppression. (C) 2017 Elsevier B.V. All rights reserved.