indan-2-yl iodomethyl carbonate | 1450666-23-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: indan-2-yl iodomethyl carbonate
• 英文别名: 2,3-dihydro-1H-inden-2-yl iodomethyl carbonate
• CAS: 1450666-23-5
• 化学式: C₁₁H₁₁IO₃
• 分子量: 318.111
• InChiKey: DRTMPNLXYQFOSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  indan-2-yl iodomethyl carbonate 、 美罗培南 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以71%的产率得到indan-2-yloxycarbonyloxymethyl (1R,5S,6S)-2-{[(3S,5S)-5-(N,N-dimethylcarbamoyl)pyrrolidin-3-yl]thio}-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate
  参考文献：
  名称：

  Synthesis, pH-dependent, and plasma stability of meropenem prodrugs for potential use against drug-resistant tuberculosis

  摘要：

  Meropenem, a broad-spectrum parenteral beta-lactam antibiotic, in combination with clavulanate has recently shown efficacy in patients with extensively drug-resistant tuberculosis. As a result of meropenem's short half-life and lack of oral bioavailability, the development of an oral therapy is warranted for TB treatment in underserved countries where chronic parenteral therapy is impractical. To improve the oral absorption of meropenem, several alkyloxycarbonyloxyalkyl ester prodrugs with increased lipophilicity were synthesized and their stability in physiological aqueous solutions and guinea pig as well as human plasma was evaluated. The stability of prodrugs in aqueous solution at pH 6.0 and 7.4 was significantly dependent on the ester promoiety with the major degradation product identified as the parent compound meropenem. However, in simulated gastrointestinal fluid (pH 1.2) the major degradation product identified was ring-opened meropenem with the promoiety still intact, suggesting the gastrointestinal environment may reduce the absorption of meropenem prodrugs in vivo unless administered as an enteric-coated formulation. Additionally, the stability of the most aqueous stable prodrugs in guinea pig or human plasma was short, implying a rapid release of parent meropenem. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.024
• 作为产物：
  描述：

  indan-2-yl chloromethyl carbonate 在 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 5.0h， 生成 indan-2-yl iodomethyl carbonate
  参考文献：
  名称：

  Synthesis, pH-dependent, and plasma stability of meropenem prodrugs for potential use against drug-resistant tuberculosis

  摘要：

  Meropenem, a broad-spectrum parenteral beta-lactam antibiotic, in combination with clavulanate has recently shown efficacy in patients with extensively drug-resistant tuberculosis. As a result of meropenem's short half-life and lack of oral bioavailability, the development of an oral therapy is warranted for TB treatment in underserved countries where chronic parenteral therapy is impractical. To improve the oral absorption of meropenem, several alkyloxycarbonyloxyalkyl ester prodrugs with increased lipophilicity were synthesized and their stability in physiological aqueous solutions and guinea pig as well as human plasma was evaluated. The stability of prodrugs in aqueous solution at pH 6.0 and 7.4 was significantly dependent on the ester promoiety with the major degradation product identified as the parent compound meropenem. However, in simulated gastrointestinal fluid (pH 1.2) the major degradation product identified was ring-opened meropenem with the promoiety still intact, suggesting the gastrointestinal environment may reduce the absorption of meropenem prodrugs in vivo unless administered as an enteric-coated formulation. Additionally, the stability of the most aqueous stable prodrugs in guinea pig or human plasma was short, implying a rapid release of parent meropenem. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.024