N-methyl-N-[(tert-butoxycarbonyl)methyl]-7α-methoxy-8-oxo-3-{[(1,2,5,6-tetrahydro-5,6-dioxo-2-methyl-as-triazin-3-yl)thio]methyl}-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxamide 5,5-dioxide | 116536-14-2

• 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: N-methyl-N-[(tert-butoxycarbonyl)methyl]-7α-methoxy-8-oxo-3-{[(1,2,5,6-tetrahydro-5,6-dioxo-2-methyl-as-triazin-3-yl)thio]methyl}-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxamide 5,5-dioxide
• 英文别名: tert-butyl 2-[[(6R,7S)-7-methoxy-3-[(2-methyl-5,6-dioxo-1H-1,2,4-triazin-3-yl)sulfanylmethyl]-5,5,8-trioxo-5lambda6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbonyl]-methylamino]acetate；tert-butyl 2-[[(6R,7S)-7-methoxy-3-[(2-methyl-5,6-dioxo-1H-1,2,4-triazin-3-yl)sulfanylmethyl]-5,5,8-trioxo-5λ6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbonyl]-methylamino]acetate
• CAS: 116536-14-2
• 化学式: C₂₀H₂₇N₅O₉S₂
• 分子量: 545.594
• InChiKey: FDLPQXITLHXEKT-SCLBCKFNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  206
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-methyl-N-[(tert-butoxycarbonyl)methyl]-7α-methoxy-8-oxo-3-{[(1,2,5,6-tetrahydro-5,6-dioxo-2-methyl-as-triazin-3-yl)thio]methyl}-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 1.0h， 以37%的产率得到N-methyl-N-(carboxymethyl)-7α-methoxy-8-oxo-3-{[(1,2,5,6-tetrahydro-5,6-dioxo-2-methyl-as-triazin-3-yl)thio]methyl}-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. 4. Selection of a substituted cephalosporin (L-658,758) as a topical aerosol

  摘要：

  Human leukocyte elastase (HLE) is a serine protease which has been implicated as a causative agent in several pulmonary diseases. The continued modification of our previously reported cephalosporin-based HLE inhibitors has led to the identification of a series of C-2 amides with potent, topical activity in an in vivo hamster lung hemorrhage model. While the most potent in vitro HLE inhibition had previously been obtained with lipophilic ester derivatives, it was found that the less active, but more polar and stable, amide derivatives were much more effective in vivo. The development of the structure-activity relations for optimization of these activities is discussed. These results led to the selection of 3-(acetoxymethyl)-2-[(2(S)-carboxypyrrolidino)carbonyl]-7alpha-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene 5,5-dioxide (3, L-658,758) as a selective, potent, time-dependent HLE inhibitor suitable for formulation as a topical aerosol drug for possible clinical use.

  DOI：

  10.1021/jm00099a002
• 作为产物：
  描述：

  [((6R,7S)-3-Hydroxymethyl-7-methoxy-5,5,8-trioxo-5λ⁶-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carbonyl)-methyl-amino]-acetic acid tert-butyl ester 在 吡啶 、 氯化亚砜 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 16.5h， 生成 N-methyl-N-[(tert-butoxycarbonyl)methyl]-7α-methoxy-8-oxo-3-{[(1,2,5,6-tetrahydro-5,6-dioxo-2-methyl-as-triazin-3-yl)thio]methyl}-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. 4. Selection of a substituted cephalosporin (L-658,758) as a topical aerosol

  摘要：

  Human leukocyte elastase (HLE) is a serine protease which has been implicated as a causative agent in several pulmonary diseases. The continued modification of our previously reported cephalosporin-based HLE inhibitors has led to the identification of a series of C-2 amides with potent, topical activity in an in vivo hamster lung hemorrhage model. While the most potent in vitro HLE inhibition had previously been obtained with lipophilic ester derivatives, it was found that the less active, but more polar and stable, amide derivatives were much more effective in vivo. The development of the structure-activity relations for optimization of these activities is discussed. These results led to the selection of 3-(acetoxymethyl)-2-[(2(S)-carboxypyrrolidino)carbonyl]-7alpha-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene 5,5-dioxide (3, L-658,758) as a selective, potent, time-dependent HLE inhibitor suitable for formulation as a topical aerosol drug for possible clinical use.

  DOI：

  10.1021/jm00099a002