1-N-[(2S)-1-[(2S)-2-[[(2S)-1-(1,3-benzoxazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-4-N-(4-chlorophenyl)sulfonylbenzene-1,4-dicarboxamide

• 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: 1-N-[(2S)-1-[(2S)-2-[[(2S)-1-(1,3-benzoxazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-4-N-(4-chlorophenyl)sulfonylbenzene-1,4-dicarboxamide
• 化学式: C₃₆H₄₀ClN₅O₈S
• 分子量: 738.261
• InChiKey: SAAKOEDFEWDVEM-QESFDJMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  51
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  196
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-N-[(2S)-1-[(2S)-2-[[(2S)-1-(1,3-benzoxazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-4-N-(4-chlorophenyl)sulfonylbenzene-1,4-dicarboxamide 在 戴斯-马丁氧化剂 、 叔丁醇 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以61%的产率得到N1-((S)-1-((S)-2-(((S)-1-(benzo[d]oxazol-2-yl)-3-methyl-1-oxobutan-2-yl)carbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)-N4-(4-chlorophenylsulfonyl)terephthalamide
  参考文献：
  名称：

  Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 3. In vitro and in vivo potency of a series of peptidyl .alpha.-ketobenzoxazoles

  摘要：

  A series of peptidyl alpha-ketobenzoxazoles were synthesized and evaluated for their in vitro and in vivo inhibition of human neutrophil elastase (HNE). These compounds inhibit HNE by forming both a covalent bond between the ketone carbonyl carbon atom and the hydroxyl group of Ser-195 and a hydrogen bond between the benzoxazole nitrogen atom and His-57. Appending to the parent benzoxazole ring a variety of substituents which spanned a range of physicochemical properties had only a modest effect on in, vitro potency (K-i = 3-0.4 nM). This apparent lack of a significant effect is believed to result from the fact that any increased ketone carbonyl activation by the ring substituent is counter balanced by a corresponding decrease in the hydrogen-bonding ability of the benzoxazole nitrogen atom. In contrast to the results in vitro, maximizing in vive activity was critically dependent upon the choice of the benzoxazole ring substituent. Several substituted peptidyl alpha-ketobenzoxazoles effectively inhibited HNE-induced lung injury when administered intratracheally 24 h prior to the enzyme.

  DOI：

  10.1021/jm00020a011
• 作为产物：
  描述：

  N-Benzyloxycarbonyl-L-valyl-L-prolyl-L-valinal 在 palladium on activated charcoal 水 、 氢气 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 乙酰氯 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 为溶剂， 25.0~60.0 ℃ 、344.73 kPa 条件下， 反应 46.5h， 生成 1-N-[(2S)-1-[(2S)-2-[[(2S)-1-(1,3-benzoxazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-4-N-(4-chlorophenyl)sulfonylbenzene-1,4-dicarboxamide
  参考文献：
  名称：

  Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 3. In vitro and in vivo potency of a series of peptidyl .alpha.-ketobenzoxazoles

  摘要：

  A series of peptidyl alpha-ketobenzoxazoles were synthesized and evaluated for their in vitro and in vivo inhibition of human neutrophil elastase (HNE). These compounds inhibit HNE by forming both a covalent bond between the ketone carbonyl carbon atom and the hydroxyl group of Ser-195 and a hydrogen bond between the benzoxazole nitrogen atom and His-57. Appending to the parent benzoxazole ring a variety of substituents which spanned a range of physicochemical properties had only a modest effect on in, vitro potency (K-i = 3-0.4 nM). This apparent lack of a significant effect is believed to result from the fact that any increased ketone carbonyl activation by the ring substituent is counter balanced by a corresponding decrease in the hydrogen-bonding ability of the benzoxazole nitrogen atom. In contrast to the results in vitro, maximizing in vive activity was critically dependent upon the choice of the benzoxazole ring substituent. Several substituted peptidyl alpha-ketobenzoxazoles effectively inhibited HNE-induced lung injury when administered intratracheally 24 h prior to the enzyme.

  DOI：

  10.1021/jm00020a011