2-(1-氯乙氧基)-1,3-二异丙基苯 | 1042134-77-9

• 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: 2-(1-氯乙氧基)-1,3-二异丙基苯
• 英文名称: 2-(1-chloroethoxy)-1,3-diisopropylbenzene
• 英文别名: 2-(1-chloro-ethoxy)-1,3-diisopropyl-benzene；2-(1-Chloroethoxy)-1,3-di(propan-2-yl)benzene
• CAS: 1042134-77-9
• 化学式: C₁₄H₂₁ClO
• 分子量: 240.773
• InChiKey: PQUOXKAQMFOXFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(1-氯乙氧基)-1,3-二异丙基苯 在 三乙胺 、 tetrabutylammonium phosphate 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以28%的产率得到phosphoric acid mono[1-(2,6-diisopropylphenoxy)ethyl] ester disodium
  参考文献：
  名称：

  Synthesis, in vitro and in vivo characterization of novel ethyl dioxy phosphate prodrug of propofol

  摘要：

  A novel ethyl dioxy phosphate prodrug of propofol (3) was synthesized and characterized in vitro and in vivo as safer alternative for phosphonooxymethyl prodrugs. The synthesis of 3 was achieved via vinyl and 1-chloroethyl ether intermediates, followed by addition of phosphate group. Aqueous solubility and chemical stability of 3 was determined in buffer solutions and the bioconversion of 3 to propofol was determined in vitro and in vivo. The results show that 3 greatly enhanced the aqueous solubility of propofol (solubility over 10 mg/mL) and the stability in buffer solution (t(1/2) = 5.2 +/- 0.2 days at pH 7.4, r.t.) was sufficient for i.v. administration. The enzymatic hydrolysis of 3 to propofol was extremely rapid in Vitro (t(1/2) = 21 +/- 3 s) and 3 was readily converted to propofol in vivo in rats. During bioconversion, 3 releases acetaldehyde, a less toxic compound than the formaldehyde released from the phosphonooxymethyl prodrug of propofol (Aquavan), currently undergoing clinical trials. The maximum plasma concentration of propofol, 3.0 +/- 10.2 mu g/mL, was reached within 2.1 +/- 0.8 min after the i.v. administration of 3. The present study indicates that ethyl dioxy phosphate represents a potentially useful water-soluble prodrug structure suitable for i.v. administration. (C) 2008 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2008.02.121
• 作为产物：
  描述：

  2,6-i-Propyl-phenylvinylsulfid 以 乙酸乙酯 为溶剂， 100.0 ℃ 、500.01 kPa 条件下， 反应 0.17h， 生成 2-(1-氯乙氧基)-1,3-二异丙基苯
  参考文献：
  名称：

  Synthesis, in vitro and in vivo characterization of novel ethyl dioxy phosphate prodrug of propofol

  摘要：

  A novel ethyl dioxy phosphate prodrug of propofol (3) was synthesized and characterized in vitro and in vivo as safer alternative for phosphonooxymethyl prodrugs. The synthesis of 3 was achieved via vinyl and 1-chloroethyl ether intermediates, followed by addition of phosphate group. Aqueous solubility and chemical stability of 3 was determined in buffer solutions and the bioconversion of 3 to propofol was determined in vitro and in vivo. The results show that 3 greatly enhanced the aqueous solubility of propofol (solubility over 10 mg/mL) and the stability in buffer solution (t(1/2) = 5.2 +/- 0.2 days at pH 7.4, r.t.) was sufficient for i.v. administration. The enzymatic hydrolysis of 3 to propofol was extremely rapid in Vitro (t(1/2) = 21 +/- 3 s) and 3 was readily converted to propofol in vivo in rats. During bioconversion, 3 releases acetaldehyde, a less toxic compound than the formaldehyde released from the phosphonooxymethyl prodrug of propofol (Aquavan), currently undergoing clinical trials. The maximum plasma concentration of propofol, 3.0 +/- 10.2 mu g/mL, was reached within 2.1 +/- 0.8 min after the i.v. administration of 3. The present study indicates that ethyl dioxy phosphate represents a potentially useful water-soluble prodrug structure suitable for i.v. administration. (C) 2008 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2008.02.121

文献信息

• [EN] WATER-SOLUBLE ETHYLIDENE PHOSPHATE PRODRUG OF PROPOFOL<br/>[FR] PROMÉDICAMENT SOLUBLE DANS L'EAU ÉTHYLIDÈNE PHOSPHATE DE PROPOFOL
  申请人：FENNOPHARMA OY

  公开号：WO2009016269A1

  公开（公告）日：2009-02-05

  The present invention concerns a novel water-soluble prodrug, ethyl dioxy phosphate of propofol, as well as the nontoxic pharmaceutically acceptable salts thereof, methods for preparing the prodrug, pharmaceutical compositions containing the prodrug, and methods for using the prodrug.

  本发明涉及一种新型水溶性前药，丙泊酚的乙氧基磷酸酯，以及其无毒的药学上可接受的盐，制备该前药的方法，包含该前药的制药组合物以及使用该前药的方法。