benzyl N-[(2S)-1-[(2S)-2-[[(2S)-1-(1H-benzimidazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate | 1026520-48-8

• 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-(1H-benzimidazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 1026520-48-8
• 化学式: C₃₀H₃₉N₅O₅
• 分子量: 549.67
• InChiKey: UKVCEUQUHUMSDN-SWFVVNKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  benzyl N-[(2S)-1-[(2S)-2-[[(2S)-1-(1H-benzimidazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate 在 邻苯二甲酸二甲酯 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 反应 16.0h， 以55%的产率得到(S)-(benzyloxycarbonyl)-L-valyl-N-<1-<(2-benzimidazolyl)carbonyl>-2-methylpropyl>-L-prolinamide
  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 乙酰氯 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 水 为溶剂， 反应 24.5h， 生成 benzyl N-[(2S)-1-[(2S)-2-[[(2S)-1-(1H-benzimidazol-2-yl)-1-hydroxy-3-methylbutan-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