chloromethyl <2S-(2α,5α,6β)>-3,3-dimethyl-7-oxo-6-(2,6-dimethoxybenzamido)-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate | 34582-70-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: chloromethyl <2S-(2α,5α,6β)>-3,3-dimethyl-7-oxo-6-(2,6-dimethoxybenzamido)-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate
• 英文别名: Chloromethyl [2S-(2α,5α,6β)]-3,3-dimethyl-7-oxo-6-[(2,6-dimethoxy)benzamido]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate；chloromethyl (2S-(2α,5α,6β))-3,3-dimethyl-7-oxo-6-(2,6-dimethoxybenzamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate；chloromethyl (2S,5R,6R)-6-[(2,6-dimethoxybenzoyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
• CAS: 34582-70-2
• 化学式: C₁₈H₂₁ClN₂O₆S
• 分子量: 428.894
• InChiKey: QFNIFEXENYXYPJ-DVOMOZLQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  chloromethyl <2S-(2α,5α,6β)>-3,3-dimethyl-7-oxo-6-(2,6-dimethoxybenzamido)-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate 在 sodium dithionite 、 碳酸氢钠 作用下， 以 硝基甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 313.17h， 生成 <<(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl>oxy>methyl <2S-(2α,5α,6β)>-3,3-dimethyl-7-oxo-6-(2,6-dimethoxybenzamido)-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate
  参考文献：
  名称：

  Chemical delivery systems for some penicillinase-resistant semisynthetic penicillins

  摘要：

  Chemical delivery systems (CDS's) based on a dihydropyridine----quaternary pyridinium ion redox system analogous to the naturally occurring NADH----NAD+ system were synthesized for a group of staphylococcal penicillinase resistant penicillins, including methicillin, oxacillin, cloxacillin, and dicloxacillin, in order to improve their penetration of the central nervous system (CNS). The CDS's are penicillin monoesters of gem-diols in which the other hydroxyl group is esterified by the dihydrotrigonelline carrier. The CDS's were found to be much more lipopholic than the parent drugs by comparing their log k' values used as lipophilicity indexes. A study of the chemical oxidation of the CDS's performed by a UV spectrophotometric method showed relatively slow reaction. Stability studies were performed in buffers and different animal tissues for both the CDS's and the quaternary salt type derivatives. These studies showed that the CDS's were oxidized to the quaternary salt forms at neutral and basic pH and added water at lower pH. The quaternary salts released the parent drugs both in buffers and in vitro. A preliminary in vivo distribution study in the rat and rabbit demonstrated blood-brain barrier (BBB) penetration by the CDS, whereas no drug was detected by administering the drug itself.

  DOI：

  10.1021/jm00128a021
• 作为产物：
  描述：

  氯甲基氯磺酸酯 、 methicillin sodium 在 碳酸氢钠 、 tetra(n-butyl)ammonium hydrogen sulfate 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 chloromethyl <2S-(2α,5α,6β)>-3,3-dimethyl-7-oxo-6-(2,6-dimethoxybenzamido)-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate
  参考文献：
  名称：

  Pharmaceutical formulations for parenteral use

  摘要：

  药物的水性无菌溶液，这些药物在水中不溶或仅微溶，或在水中不稳定，与从羟丙基、羟乙基、葡萄糖基、麦芽糖基和麦芽三糖基衍生的β-和γ-环糊精中选择的环糊精结合，提供了一种缓解与静脉注射后药物在注射部位和/或在肺部或其他器官沉淀问题相关的手段。

  公开号：

  US05024998A1

文献信息

• POP, EMIL;WU, WHEI-MEI;BODOR, NICOLAS, J. MED. CHEM., 32,(1989) N, C. 1789-1795
  作者：POP, EMIL、WU, WHEI-MEI、BODOR, NICOLAS

  DOI：——

  日期：——
• Chemical delivery systems for some penicillinase-resistant semisynthetic penicillins
  作者：Emil Pop、Whei Mei Wu、Nicholas Bodor

  DOI：10.1021/jm00128a021

  日期：1989.8

  Chemical delivery systems (CDS's) based on a dihydropyridine----quaternary pyridinium ion redox system analogous to the naturally occurring NADH----NAD+ system were synthesized for a group of staphylococcal penicillinase resistant penicillins, including methicillin, oxacillin, cloxacillin, and dicloxacillin, in order to improve their penetration of the central nervous system (CNS). The CDS's are penicillin monoesters of gem-diols in which the other hydroxyl group is esterified by the dihydrotrigonelline carrier. The CDS's were found to be much more lipopholic than the parent drugs by comparing their log k' values used as lipophilicity indexes. A study of the chemical oxidation of the CDS's performed by a UV spectrophotometric method showed relatively slow reaction. Stability studies were performed in buffers and different animal tissues for both the CDS's and the quaternary salt type derivatives. These studies showed that the CDS's were oxidized to the quaternary salt forms at neutral and basic pH and added water at lower pH. The quaternary salts released the parent drugs both in buffers and in vitro. A preliminary in vivo distribution study in the rat and rabbit demonstrated blood-brain barrier (BBB) penetration by the CDS, whereas no drug was detected by administering the drug itself.
• Pharmaceutical formulations for parenteral use
  申请人：University of Florida

  公开号：US04983586A1

  公开（公告）日：1991-01-08

  Aqueous parenteral solutions of drugs which are insoluble or only sparingly soluble in water and/or which are unstable in water, combined with hydroxypropyl-.beta.-cyclodextrin, provide a means for alleviating problems associated with drug precipitation at the injection site and/or in the lungs or other organs following parenteral administration.

  将不溶或在水中仅微溶或在水中不稳定的药物与羟丙基-β-环糊精结合，提供了一种缓解与药物在注射部位沉淀以及/或在注射后在肺部或其他器官中沉淀相关问题的方法。