N-benzyloxycarbonyl-L-valyl-N-[(1S)-3-benzylamino-2-hydroxy-1-isopropyl-3-oxopropyl]-L-prolinamide | 291778-46-6

• 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-benzyloxycarbonyl-L-valyl-N-[(1S)-3-benzylamino-2-hydroxy-1-isopropyl-3-oxopropyl]-L-prolinamide
• 英文别名: Cbz-Val-Pro-bAla(2-OH,3S-iPr)-NHBn；benzyl N-[(2S)-1-[(2S)-2-[[(3S)-1-(benzylamino)-2-hydroxy-4-methyl-1-oxopentan-3-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 291778-46-6
• 化学式: C₃₁H₄₂N₄O₆
• 分子量: 566.698
• InChiKey: PKKRJUFWOYFHNV-QPWGPPCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  137
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonyl-L-valyl-N-[(1S)-3-benzylamino-2-hydroxy-1-isopropyl-3-oxopropyl]-L-prolinamide 在 20 % Pd(OH)2/C on charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 L-valyl-N-[(1S)-(3-benzylamino-1-isopropyl-2-hydroxy-3-oxo-propyl)]-L-prolinamide
  参考文献：
  名称：

  Development of a highly water-soluble peptide-based human neutrophil elastase inhibitor; AE-3763 for treatment of acute organ injury

  摘要：

  A series of peptide-based transition-state human neutrophil elastase (HNE) inhibitors with N-terminal acidic moieties were synthesized and their inhibitory activity against HNE was evaluated both in vitro and in vivo. Our results show that compounds containing cyclic amide bridged acidic moieties at the N-terminal have not only improved water solubility but also high in vivo potency. Among these compounds, AE-3763 showed remarkable efficacy in hamster models of elastase-induced lung hemorrhage and lipopolysaccharide (LPS)-induced lung injury as well as in a mouse model of LPS/galactosamine-induced acute multiple organ dysfunctions. The water solubility of AE-3763 (>1000 mg/ml in H(2)O) was also far superior to that of any of the other compounds synthesized. Thus, it is believed that AE-3763 would be useful for treatment of HNE-associated respiratory disorders, such as acute respiratory distress syndrome (ARDS), acute lung injury (ALI), and acute exacerbation of chronic obstructive pulmonary disease (COPD). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.020
• 作为产物：
  描述：

  (3S)-3-amino-N-benzyl-2-hydroxy-4-methylpentanamide 、 N-benzyloxycarbonyl-L-valyl-L-proline 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以4.6 g的产率得到N-benzyloxycarbonyl-L-valyl-N-[(1S)-3-benzylamino-2-hydroxy-1-isopropyl-3-oxopropyl]-L-prolinamide
  参考文献：
  名称：

  Development of a highly water-soluble peptide-based human neutrophil elastase inhibitor; AE-3763 for treatment of acute organ injury

  摘要：

  A series of peptide-based transition-state human neutrophil elastase (HNE) inhibitors with N-terminal acidic moieties were synthesized and their inhibitory activity against HNE was evaluated both in vitro and in vivo. Our results show that compounds containing cyclic amide bridged acidic moieties at the N-terminal have not only improved water solubility but also high in vivo potency. Among these compounds, AE-3763 showed remarkable efficacy in hamster models of elastase-induced lung hemorrhage and lipopolysaccharide (LPS)-induced lung injury as well as in a mouse model of LPS/galactosamine-induced acute multiple organ dysfunctions. The water solubility of AE-3763 (>1000 mg/ml in H(2)O) was also far superior to that of any of the other compounds synthesized. Thus, it is believed that AE-3763 would be useful for treatment of HNE-associated respiratory disorders, such as acute respiratory distress syndrome (ARDS), acute lung injury (ALI), and acute exacerbation of chronic obstructive pulmonary disease (COPD). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.020

文献信息

• HETEROCYCLIC COMPOUNDS, INTERMEDIATES THEREOF AND ELASTASE INHIBITORS
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：EP1157998B1

  公开（公告）日：2004-02-11
• US6835714B1
  申请人：——

  公开号：US6835714B1

  公开（公告）日：2004-12-28