chloromethyl <2S-(2α,5α,6β)>-3,3-dimethyl-6-<(5-methyl-3-phenyl-4-isoxazolyl)carboxamido>-7-oxo-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate | 34582-75-7

• 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-6-<(5-methyl-3-phenyl-4-isoxazolyl)carboxamido>-7-oxo-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate
• 英文别名: chloromethyl (2S-(2α,5α,6β))-3,3-dimethyl-6-[(5-methyl-3-phenyl-4-isoxazolyl)carboxamido]-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate；chloromethyl (2S,5R,6R)-3,3-dimethyl-6-[(5-methyl-3-phenyl-1,2-oxazole-4-carbonyl)amino]-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
• CAS: 34582-75-7
• 化学式: C₂₀H₂₀ClN₃O₅S
• 分子量: 449.915
• InChiKey: CMGMAZGHHYDSOW-RVKKMQEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.55
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  101.74
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  chloromethyl <2S-(2α,5α,6β)>-3,3-dimethyl-6-<(5-methyl-3-phenyl-4-isoxazolyl)carboxamido>-7-oxo-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 289.17h， 生成 <<(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl>oxy>methyl <2S-(2α,5α,6β)>-3,3-dimethyl-6-<(5-methyl-3-phenyl-4-isoxazolyl)carboxamido>-7-oxo-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 、 Bristopen 在 四丁基硫酸氢铵 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.5h， 以1.87 g的产率得到chloromethyl <2S-(2α,5α,6β)>-3,3-dimethyl-6-<(5-methyl-3-phenyl-4-isoxazolyl)carboxamido>-7-oxo-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

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：——