tert-butyl 7α-methoxy-3-(1-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl-3-cephem-4-carboxylate 1,1-dioxide | 116561-66-1

• 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: tert-butyl 7α-methoxy-3-(1-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl-3-cephem-4-carboxylate 1,1-dioxide
• 英文别名: 1,1-dimethylethyl 7α-methoxy-3-<<(1-methyltetrazol-5-yl)thio>methyl>-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylate 5,5-dioxide；tert-butyl (6R,7S)-7-methoxy-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-5,5,8-trioxo-5lambda6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate；tert-butyl (6R,7S)-7-methoxy-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-5,5,8-trioxo-5λ6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 116561-66-1
• 化学式: C₁₅H₂₁N₅O₆S₂
• 分子量: 431.494
• InChiKey: FOCOSUSRSGEMIY-CMPLNLGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  167
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl 7α-methoxy-3-(1-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl-3-cephem-4-carboxylate 1,1-dioxide 在 吡啶 、 苯甲醚 、 三氟乙酸 、 H-pEEDSG-OH 作用下， 以 二氯甲烷 为溶剂， 反应 5.5h， 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：

  t-butyl 7α-methoxy-3-methyl-3-cephem-4-carboxylate 1,1-dioxide 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 三乙胺 作用下， 以 四氯化碳 、 乙腈 为溶剂， 反应 5.25h， 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

文献信息

• Inhibition of human leukocyte elastase. 3. Synthesis and activity of 3'-substituted cephalosporins
  作者：Shrenik K. Shah、Karen A. Brause、Gilbert O. Chandler、Paul E. Finke、Bonnie M. Ashe、Hazel Weston、Wilson B. Knight、Alan L. Maycock、James B. Doherty

  DOI：10.1021/jm00171a030

  日期：1990.9

  Several 3'-substituted cephalosporin sulfones were synthesized from 3-(hydroxymethyl)cephalosporin, which was prepared by Ti(OiPr)4 hydrolysis of the corresponding acetate. A method was also developed to prepare a 3-vinylcephalosporin. Some of these compound were found to be potent time-dependent inhibitors of human leukocyte elastase (HLE). The HLE inhibitory activity was correlated with sigma 1 and it was concluded that the potency was determined by the electron-withdrawing ability as well as the size of the substituent. A mechanism for inhibition of HLE by cephalosporin sulfones is proposed.
• Synthesis and evaluation of new elastase inhibitors. I. 1,1-Dioxocephem-4-thiolesters
  作者：M Alpegiani、A Baici、P Bissolino、P Carminati、G Cassinelli、S Del Nero、G Franceschi、P Orezzi、E Perrone、V Rizzo、N Sacchi

  DOI：10.1016/0223-5234(92)90019-w

  日期：1992.12

  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.