N-<2-<5-(benzyloxy)-1H-indol-3-yl>ethyl> (2S,3S)-3-<<(S)-3-methyl-1-<(3-methylbutyl)carbamoyl>butyl>carbamoyl>-2-oxiranecarboxamide | 140660-60-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-<2-<5-(benzyloxy)-1H-indol-3-yl>ethyl> (2S,3S)-3-<<(S)-3-methyl-1-<(3-methylbutyl)carbamoyl>butyl>carbamoyl>-2-oxiranecarboxamide
• 英文别名: (2S,3S)-2-N-[(2S)-4-methyl-1-(3-methylbutylamino)-1-oxopentan-2-yl]-3-N-[2-(5-phenylmethoxy-1H-indol-3-yl)ethyl]oxirane-2,3-dicarboxamide
• CAS: 140660-60-2
• 化学式: C₃₂H₄₂N₄O₅
• 分子量: 562.709
• InChiKey: JNBJKXCANPQSMQ-AWCRTANDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.87
• 重原子数：
  41.0
• 可旋转键数：
  15.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  124.85
• 氢给体数：
  4.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-<2-<5-(benzyloxy)-1H-indol-3-yl>ethyl> (2S,3S)-3-<<(S)-3-methyl-1-<(3-methylbutyl)carbamoyl>butyl>carbamoyl>-2-oxiranecarboxamide 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以96%的产率得到N-[2-(5-hydroxy-1H-indol-3-yl)ethyl] (2S,3S)-3-({(S)-3-methyl-1-[(3-methylbutyl)carbamoyl]butyl}carbamoyl)-2-oxiranecarboxamide
  参考文献：
  名称：

  Ester and amide derivatives of E64c as inhibitors of platelet calpains

  摘要：

  Ester and amide derivatives of E64c, (+)-(2S,3S)-3-[[(S)-3-methyl-1-[(3-methylbutyl)carbamoyl]butyl]carbamoyl]-2-oxiranecarboxylic acid, an inhibitor of calpains, were synthesized and tested for ability to inhibit calpain in lysed cells, ability to enter intact cells, and ability to inhibit calpain in intact cells. The esters were from halogen-substituted alcohols and alcohols with increasing size. There were no appreciable differences in the inhibitory potency of any of the halogen-substituted esters from ethyl to trifluoroethyl, indicating that ease of hydrolysis of this class of ester is not important for activity. The only ester with impaired activity was the largest, Z-leucyl-norleucyl, which was about 5% as effective as the ethyl ester, E64d. Amides of amino acid esters also had impaired activity. To explore the possibility of targeting E64c derivatives to specific cells, esters and amides of E64c with 5-hydroxytryptamine were tested on the rationale that the active 5-hydroxytryptamine uptake mechanism of platelets might selectively concentrate the drug in platelets. Both the ester and amide inhibited calpain in lysed cells, but only the ester inhibited in intact cells. The 5-hydroxytryptamine ester showed no advantage over the ethyl ester in entering platelets.

  DOI：

  10.1021/jm00089a015
• 作为产物：
  描述：

  阿洛司他丁 在 N-甲基吗啉 、 氢氧化钾 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 1-羟基苯并三唑 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 30.0h， 生成 N-<2-<5-(benzyloxy)-1H-indol-3-yl>ethyl> (2S,3S)-3-<<(S)-3-methyl-1-<(3-methylbutyl)carbamoyl>butyl>carbamoyl>-2-oxiranecarboxamide
  参考文献：
  名称：

  Ester and amide derivatives of E64c as inhibitors of platelet calpains

  摘要：

  Ester and amide derivatives of E64c, (+)-(2S,3S)-3-[[(S)-3-methyl-1-[(3-methylbutyl)carbamoyl]butyl]carbamoyl]-2-oxiranecarboxylic acid, an inhibitor of calpains, were synthesized and tested for ability to inhibit calpain in lysed cells, ability to enter intact cells, and ability to inhibit calpain in intact cells. The esters were from halogen-substituted alcohols and alcohols with increasing size. There were no appreciable differences in the inhibitory potency of any of the halogen-substituted esters from ethyl to trifluoroethyl, indicating that ease of hydrolysis of this class of ester is not important for activity. The only ester with impaired activity was the largest, Z-leucyl-norleucyl, which was about 5% as effective as the ethyl ester, E64d. Amides of amino acid esters also had impaired activity. To explore the possibility of targeting E64c derivatives to specific cells, esters and amides of E64c with 5-hydroxytryptamine were tested on the rationale that the active 5-hydroxytryptamine uptake mechanism of platelets might selectively concentrate the drug in platelets. Both the ester and amide inhibited calpain in lysed cells, but only the ester inhibited in intact cells. The 5-hydroxytryptamine ester showed no advantage over the ethyl ester in entering platelets.

  DOI：

  10.1021/jm00089a015