7α-methoxy-3-(1-methyl-1,2,3,4-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid 1,1-dioxide | 148115-22-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 7α-methoxy-3-(1-methyl-1,2,3,4-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid 1,1-dioxide
• CAS: 148115-22-4
• 化学式: C₁₁H₁₃N₅O₆S₂
• 分子量: 375.386
• InChiKey: AKPDRPMGVFJZAW-IONNQARKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.75
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  144.58
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  叔丁基硫醇 、 7α-methoxy-3-(1-methyl-1,2,3,4-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid 1,1-dioxide 在 吡啶 、 H-pEEDSG-OH 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 tert-butyl 7α-methoxy-3-(1-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl-3-cephem-4-carboxylate 1,1-dioxide
  参考文献：
  名称：

  Synthesis and evaluation of new elastase inhibitors. I. 1,1-Dioxocephem-4-thiolesters

  摘要：

  Several 7alpha-chloro and 7alpha-methoxy cephalosporin thiolester sulphones variously substituted at the C-3' position were synthesized from 7-amino-3-deacetoxycephalosporanic acid (7-ADCA). The compounds are time-dependent inhibitors of human leukocyte elastase (HLE) with effective K(i) ranging from micro- to nanomolar values, and second order rate constant reaching 10(6) M-1s-1; they also inhibit porcine pancreatic elastase with similar, though not identical efficiency. Compared to the corresponding cephem esters, the thiolesters of the 7-Cl series inhibit HLE up to 10 times as fast. Complete enzyme inactivation is achieved when a leaving group at C-3' (OAc or S-Het) is present, at the expense however of stability towards hydrolytic beta-lactam cleavage. In the 7-OMe series the thiolester compounds are far more stable and retain good efficiency for irreversible enzyme inhibition, superior to that displayed by the corresponding ester compounds. Three representative compounds (including one ester and two thiolesters) are shown to be effective inhibitors of HLE in the presence of insoluble elastin.

  DOI：

  10.1016/0223-5234(92)90019-w
• 作为产物：
  描述：

  tert-butyl 3-bromomethyl-7α-methoxy-3-cephem-4-carboxylate 1,1-dioxide 在 苯甲醚 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 0.75h， 生成 7α-methoxy-3-(1-methyl-1,2,3,4-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid 1,1-dioxide
  参考文献：
  名称：

  Synthesis and evaluation of new elastase inhibitors. I. 1,1-Dioxocephem-4-thiolesters

  摘要：

  Several 7alpha-chloro and 7alpha-methoxy cephalosporin thiolester sulphones variously substituted at the C-3' position were synthesized from 7-amino-3-deacetoxycephalosporanic acid (7-ADCA). The compounds are time-dependent inhibitors of human leukocyte elastase (HLE) with effective K(i) ranging from micro- to nanomolar values, and second order rate constant reaching 10(6) M-1s-1; they also inhibit porcine pancreatic elastase with similar, though not identical efficiency. Compared to the corresponding cephem esters, the thiolesters of the 7-Cl series inhibit HLE up to 10 times as fast. Complete enzyme inactivation is achieved when a leaving group at C-3' (OAc or S-Het) is present, at the expense however of stability towards hydrolytic beta-lactam cleavage. In the 7-OMe series the thiolester compounds are far more stable and retain good efficiency for irreversible enzyme inhibition, superior to that displayed by the corresponding ester compounds. Three representative compounds (including one ester and two thiolesters) are shown to be effective inhibitors of HLE in the presence of insoluble elastin.

  DOI：

  10.1016/0223-5234(92)90019-w