N-<2-(tert-butoxycarbonyl)ethyl>-3-(acetoxymethyl)-7α-methoxy-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxamide 5,5-dioxide | 128472-82-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N-<2-(tert-butoxycarbonyl)ethyl>-3-(acetoxymethyl)-7α-methoxy-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxamide 5,5-dioxide
• 英文别名: 3-[(3-Acetoxymethyl-7-methoxy-5,5,8-trioxo-5lambda*6*-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carbonyl)-amino]-propionic acid tert-butyl ester；tert-butyl 3-[[(6R,7S)-3-(acetyloxymethyl)-7-methoxy-5,5,8-trioxo-5λ6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbonyl]amino]propanoate
• CAS: 128472-82-2
• 化学式: C₁₈H₂₆N₂O₉S
• 分子量: 446.478
• InChiKey: CBYXENQRXJYOJD-WMLDXEAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  154
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-<2-(tert-butoxycarbonyl)ethyl>-3-(acetoxymethyl)-7α-methoxy-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxamide 5,5-dioxide 在 苯甲醚 、 三氟乙酸 作用下， 反应 0.5h， 以50%的产率得到N-(2-carboxyethyl)-3-(acetoxymethyl)-7α-methoxy-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxamide 5,5-dioxide
  参考文献：
  名称：

  Inhibition of human leukocyte elastase. 2. Inhibition by substituted cephalosporin esters and amides

  摘要：

  A variety of 7 alpha-methoxycephalosporin ester and amide sulfones were prepared and tested to determine the structure-activity relations for inhibition of human leukocyte elastase (HLE), a serine protease which has been implicated in several degenerative lung and tissue diseases. The most potent IC50 values were obtained with neutral, lipophilic derivatives, with the esters being more active than the amides. However, the best time-dependent inhibition in this series was observed with the p- and m-carboxybenzyl esters 7b and 7c. These results are discussed in terms of the proposed mechanism of inhibition as well as a molecular modeling study using the recently solved X-ray crystal structure of HLE.

  DOI：

  10.1021/jm00171a029
• 作为产物：
  描述：

  7-氨基头孢烷酸 在 高氯酸 、 间氯过氧苯甲酸 、 N,N'-二环己基碳二亚胺 、 亚硝酸异戊酯 作用下， 反应 22.5h， 生成 N-<2-(tert-butoxycarbonyl)ethyl>-3-(acetoxymethyl)-7α-methoxy-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxamide 5,5-dioxide
  参考文献：
  名称：

  Inhibition of human leukocyte elastase. 2. Inhibition by substituted cephalosporin esters and amides

  摘要：

  A variety of 7 alpha-methoxycephalosporin ester and amide sulfones were prepared and tested to determine the structure-activity relations for inhibition of human leukocyte elastase (HLE), a serine protease which has been implicated in several degenerative lung and tissue diseases. The most potent IC50 values were obtained with neutral, lipophilic derivatives, with the esters being more active than the amides. However, the best time-dependent inhibition in this series was observed with the p- and m-carboxybenzyl esters 7b and 7c. These results are discussed in terms of the proposed mechanism of inhibition as well as a molecular modeling study using the recently solved X-ray crystal structure of HLE.

  DOI：

  10.1021/jm00171a029

文献信息

• FINKE, PAUL E.;ASHE, BONNIE M.;KNIGHT, WILSON B.;MAYCOCK, ALAN L.;NAVIA, +, J. MED. CHEM., 33,(1990) N, C. 2522-2528
  作者：FINKE, PAUL E.、ASHE, BONNIE M.、KNIGHT, WILSON B.、MAYCOCK, ALAN L.、NAVIA, +

  DOI：——

  日期：——
• Inhibition of human leukocyte elastase. 2. Inhibition by substituted cephalosporin esters and amides
  作者：Paul E. Finke、Bonnie M. Ashe、Wilson B. Knight、Alan L. Maycock、Manuel A. Navia、Shrenik K. Shah、Kevan R. Thompson、Dennis J. Underwood、Hazel Weston

  DOI：10.1021/jm00171a029

  日期：1990.9

  A variety of 7 alpha-methoxycephalosporin ester and amide sulfones were prepared and tested to determine the structure-activity relations for inhibition of human leukocyte elastase (HLE), a serine protease which has been implicated in several degenerative lung and tissue diseases. The most potent IC50 values were obtained with neutral, lipophilic derivatives, with the esters being more active than the amides. However, the best time-dependent inhibition in this series was observed with the p- and m-carboxybenzyl esters 7b and 7c. These results are discussed in terms of the proposed mechanism of inhibition as well as a molecular modeling study using the recently solved X-ray crystal structure of HLE.