(2S,5S,11bR)-2-(furan-2-carbonyl)amino-5-methoxycarbonyl-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole | 342648-05-9

• 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: (2S,5S,11bR)-2-(furan-2-carbonyl)amino-5-methoxycarbonyl-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole
• 英文别名: methyl (2S,5S,11bR)-2-(furan-2-carbonylamino)-3-oxo-1,2,5,6,11,11b-hexahydroindolizino[8,7-b]indole-5-carboxylate
• CAS: 342648-05-9
• 化学式: C₂₁H₁₉N₃O₅
• 分子量: 393.399
• InChiKey: ZNIUDQSEGGCJHB-XHSDSOJGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,5S,11bR)-2-(furan-2-carbonyl)amino-5-methoxycarbonyl-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 以95%的产率得到(2S,5S,11bR)-2-[(Furan-2-carbonyl)-amino]-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole-5-carboxylic acid
  参考文献：
  名称：

  Conformationally constrained analogues of endogenous tripeptide inhibitors of zinc metalloproteinases

  摘要：

  Two diastereomeric furan-2-carbonylamino-3-oxohexahydroindolizino[8,7-b]indole carboxylates, highly constrained analogues of endogenous pyroglutamyl tripeptide inhibitors of snake venom endopeptidases, have been prepared as potential inhibitors of adamalysin II and matrix metalloproteinases. They proved to be inactive against adamalysin II and weak inhibitors of gelatinase A, gelatinase B, stromelysin 1 and human neutrophyl collagenase. Evaluation of the mode of binding of the (2R,5S,11bR) isomer in the active site of adamalysin II suggests that the decrease of potency may be due to the reorientation of the acylamino chain in three of the heterocyclic nucleus, to a short contact at the entrance of the S-1' hydrophobic cleft and to the loss of flexibility of the tetracyclic nucleus in the P-1', P-2' region of the inhibitor, which prevents optimal arrangement in the S-1' specificity subsite. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)01192-2
• 作为产物：
  描述：

  (2S,5S,11bR)-2-(benzyloxycarbonyl)amino-5-methoxycarbonyl-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino<8,7-b>indole 在 palladium on activated charcoal 甲酸铵 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 生成 (2S,5S,11bR)-2-(furan-2-carbonyl)amino-5-methoxycarbonyl-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole
  参考文献：
  名称：

  Conformationally constrained analogues of endogenous tripeptide inhibitors of zinc metalloproteinases

  摘要：

  Two diastereomeric furan-2-carbonylamino-3-oxohexahydroindolizino[8,7-b]indole carboxylates, highly constrained analogues of endogenous pyroglutamyl tripeptide inhibitors of snake venom endopeptidases, have been prepared as potential inhibitors of adamalysin II and matrix metalloproteinases. They proved to be inactive against adamalysin II and weak inhibitors of gelatinase A, gelatinase B, stromelysin 1 and human neutrophyl collagenase. Evaluation of the mode of binding of the (2R,5S,11bR) isomer in the active site of adamalysin II suggests that the decrease of potency may be due to the reorientation of the acylamino chain in three of the heterocyclic nucleus, to a short contact at the entrance of the S-1' hydrophobic cleft and to the loss of flexibility of the tetracyclic nucleus in the P-1', P-2' region of the inhibitor, which prevents optimal arrangement in the S-1' specificity subsite. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)01192-2

文献信息

• Conformationally constrained analogues of endogenous tripeptide inhibitors of zinc metalloproteinases
  作者：S D'Alessio

  DOI：10.1016/s0223-5234(00)01192-2

  日期：2001.1

  Two diastereomeric furan-2-carbonylamino-3-oxohexahydroindolizino[8,7-b]indole carboxylates, highly constrained analogues of endogenous pyroglutamyl tripeptide inhibitors of snake venom endopeptidases, have been prepared as potential inhibitors of adamalysin II and matrix metalloproteinases. They proved to be inactive against adamalysin II and weak inhibitors of gelatinase A, gelatinase B, stromelysin 1 and human neutrophyl collagenase. Evaluation of the mode of binding of the (2R,5S,11bR) isomer in the active site of adamalysin II suggests that the decrease of potency may be due to the reorientation of the acylamino chain in three of the heterocyclic nucleus, to a short contact at the entrance of the S-1' hydrophobic cleft and to the loss of flexibility of the tetracyclic nucleus in the P-1', P-2' region of the inhibitor, which prevents optimal arrangement in the S-1' specificity subsite. (C) 2001 Editions scientifiques et medicales Elsevier SAS.