2-tert-butyl 3-ethyl-2-azabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate

• 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: 2-tert-butyl 3-ethyl-2-azabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate
• 英文别名: ethyl (1R,3R,4S)-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate
• 化学式: C₉H₁₃NO₂
• 分子量: 167.208
• InChiKey: PPUKEAWMRSOSSL-GJMOJQLCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-tert-butyl 3-ethyl-2-azabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 (1S,3R,4R)-2-azabicyclo[2.2.1]heptane-3-(R)-methylmethanol
  参考文献：
  名称：

  (1S, 3R, 4R)-2-Azanorbornyl-3-methanol oxazaborolidines in the asymmetric reduction of ketones

  摘要：

  Synthesis of new rigid (1S, 3R, 4R)-2-azanorbornyl-3-methanols and its application in the asymmetric borane reduction of ketones are described. The influence of temperature, solvent and concentration on the reaction outcome were also studied and enantiomeric excess up to 89% could be obtained. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(98)00424-4
• 作为产物：
  描述：

  (1R,3R,4S)-2-<(1S)-phenylethyl>-2-aza-bicyclo<2.2.1>hept-5-ene-3-carboxylic acid ethyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 48.0h， 以98%的产率得到2-tert-butyl 3-ethyl-2-azabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate
  参考文献：
  名称：

  (1S, 3R, 4R)-2-Azanorbornyl-3-methanol oxazaborolidines in the asymmetric reduction of ketones

  摘要：

  Synthesis of new rigid (1S, 3R, 4R)-2-azanorbornyl-3-methanols and its application in the asymmetric borane reduction of ketones are described. The influence of temperature, solvent and concentration on the reaction outcome were also studied and enantiomeric excess up to 89% could be obtained. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(98)00424-4

文献信息

• Design, Synthesis and Biological Evaluation of Neogliptin, a Novel 2-Azabicyclo[2.2.1]heptane-Based Inhibitor of Dipeptidyl Peptidase-4 (DPP-4)
  作者：Ivan O. Maslov、Tatiana V. Zinevich、Olga G. Kirichenko、Mikhail V. Trukhan、Sergey V. Shorshnev、Natalya O. Tuaeva、Maxim A. Gureev、Amelia D. Dahlén、Yuri B. Porozov、Helgi B. Schiöth、Vladimir M. Trukhan

  DOI：10.3390/ph15030273

  日期：——

  5-trifluorophenyl)butanoic acid substituted with bicyclic amino moiety (2-aza-bicyclo[2.2.1]heptane) were designed using molecular modelling methods, synthesised, and found to be potent DPP-4 (dipeptidyl peptidase-4) inhibitors. Compound 12a (IC50 = 16.8 ± 2.2 nM), named neogliptin, is a more potent DPP-4 inhibitor than vildagliptin and sitagliptin. Neogliptin interacts with key DPP-4 residues in the active site

  使用分子建模方法设计了含有被双环氨基部分（2-氮杂-双环[2.2.1]庚烷）取代的（R）-3-氨基-4-（2,4,5-三氟苯基）丁酸的化合物，合成，并被发现是有效的 DPP-4（二肽基肽酶 4）抑制剂。化合物 12a (IC50 = 16.8 ± 2.2 nM)，名为新格列汀，是比维格列汀和西格列汀更有效的 DPP-4 抑制剂。新格列汀与活性位点中的关键 DPP-4 残基相互作用，并具有与维格列汀和西格列汀相似的药效团参数。与西格列汀相比，它被发现具有较低的心脏毒性作用，并且在 ADME 特性方面优于维格列汀。此外，由于其低分子内环化电位，化合物 12a 在水溶液中是稳定的。