3-[((6R,7S)-3-Acetoxymethyl-7-methoxy-5,5,8-trioxo-5λ⁶-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carbonyl)-methyl-amino]-propionic acid | 128472-90-2

• 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: 3-[((6R,7S)-3-Acetoxymethyl-7-methoxy-5,5,8-trioxo-5λ⁶-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carbonyl)-methyl-amino]-propionic acid
• 英文别名: 3-[[(6R,7S)-3-(acetyloxymethyl)-7-methoxy-5,5,8-trioxo-5lambda6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbonyl]-methylamino]propanoic acid；3-[[(6R,7S)-3-(acetyloxymethyl)-7-methoxy-5,5,8-trioxo-5λ6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbonyl]-methylamino]propanoic acid
• CAS: 128472-90-2
• 化学式: C₁₅H₂₀N₂O₉S
• 分子量: 404.398
• InChiKey: DJAYLAJFNFIOLJ-SWLSCSKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  156
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-[((6R,7S)-3-Acetoxymethyl-7-methoxy-5,5,8-trioxo-5λ⁶-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carbonyl)-methyl-amino]-propionic acid 、 重氮甲烷 以 甲醇 、 乙醚 为溶剂， 以80%的产率得到3-[((6R,7S)-3-Acetoxymethyl-7-methoxy-5,5,8-trioxo-5λ⁶-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carbonyl)-methyl-amino]-propionic acid methyl ester
  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：

  (6R,7S)-3-(acetoxymethyl)-7-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 在 吡啶 、 苯甲醚 、 间氯过氧苯甲酸 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 生成 3-[((6R,7S)-3-Acetoxymethyl-7-methoxy-5,5,8-trioxo-5λ⁶-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carbonyl)-methyl-amino]-propionic acid
  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

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：——