benzyl N-[(2S)-1-[(2S)-2-[[(2S)-1-hydroxy-3-methyl-1-[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]butan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate | 1026319-41-4

• 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: benzyl N-[(2S)-1-[(2S)-2-[[(2S)-1-hydroxy-3-methyl-1-[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]butan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 1026319-41-4
• 化学式: C₂₇H₄₀N₄O₆
• 分子量: 516.638
• InChiKey: UKPVMAXWFOSZKY-RUNIQBHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  benzyl N-[(2S)-1-[(2S)-2-[[(2S)-1-hydroxy-3-methyl-1-[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]butan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate 在 草酰氯 、 二甲基亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以59%的产率得到((S)-2-Methyl-1-{(S)-2-[(S)-2-methyl-1-((S)-4-methyl-4,5-dihydro-oxazole-2-carbonyl)-propylcarbamoyl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid benzyl ester
  参考文献：
  名称：

  Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 2. Effect of varying the heterocyclic ring on in vitro potency

  摘要：

  A series of peptidyl alpha-ketoheterocycles were synthesized and evaluated for their in vitro inhibition of human neutrophil elastase (HNE). Several heterocycles, including oxazoline and benzoxazole, afforded extremely potent inhibitors of HNE (1p-r) with nanomolar to subnanomolar K-i values. The structure-activity relationships revealed that for compounds with a K-i < 1000 nM potency tends to be positively correlated with the sigma(I) value of the heterocycle. Furthermore, the results in this study support the hypothesis that, in the covalent enzyme-inhibitor adduct, the azole nitrogen atom of the inhibitor heterocycle participates in a hydrogen-bonding interaction with the active-site His-57.

  DOI：

  10.1021/jm00001a013
• 作为产物：
  描述：

  N-Benzyloxycarbonyl-L-valyl-L-prolyl-L-valinal 在 三乙胺 、 乙酰氯 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 36.5h， 生成 benzyl N-[(2S)-1-[(2S)-2-[[(2S)-1-hydroxy-3-methyl-1-[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]butan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
  参考文献：
  名称：

  Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 2. Effect of varying the heterocyclic ring on in vitro potency

  摘要：

  A series of peptidyl alpha-ketoheterocycles were synthesized and evaluated for their in vitro inhibition of human neutrophil elastase (HNE). Several heterocycles, including oxazoline and benzoxazole, afforded extremely potent inhibitors of HNE (1p-r) with nanomolar to subnanomolar K-i values. The structure-activity relationships revealed that for compounds with a K-i < 1000 nM potency tends to be positively correlated with the sigma(I) value of the heterocycle. Furthermore, the results in this study support the hypothesis that, in the covalent enzyme-inhibitor adduct, the azole nitrogen atom of the inhibitor heterocycle participates in a hydrogen-bonding interaction with the active-site His-57.

  DOI：

  10.1021/jm00001a013

文献信息

• Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 2. Effect of varying the heterocyclic ring on in vitro potency
  作者：Philip D. Edwards、Donald J. Wolanin、Donald W. Andisik、Matthew W. Davis

  DOI：10.1021/jm00001a013

  日期：1995.1

  A series of peptidyl alpha-ketoheterocycles were synthesized and evaluated for their in vitro inhibition of human neutrophil elastase (HNE). Several heterocycles, including oxazoline and benzoxazole, afforded extremely potent inhibitors of HNE (1p-r) with nanomolar to subnanomolar K-i values. The structure-activity relationships revealed that for compounds with a K-i < 1000 nM potency tends to be positively correlated with the sigma(I) value of the heterocycle. Furthermore, the results in this study support the hypothesis that, in the covalent enzyme-inhibitor adduct, the azole nitrogen atom of the inhibitor heterocycle participates in a hydrogen-bonding interaction with the active-site His-57.