2,5-cis-dicarbamoylpyrrolidine-1-carboxylic acid tert-butyl ester | 866396-75-0

• 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: 2,5-cis-dicarbamoylpyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (2S,5R)-2,5-dicarbamoylpyrrolidine-1-carboxylate
• CAS: 866396-75-0
• 化学式: C₁₁H₁₉N₃O₄
• 分子量: 257.29
• InChiKey: XIAUNUQVILOUOK-KNVOCYPGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,5-cis-dicarbamoylpyrrolidine-1-carboxylic acid tert-butyl ester 在 咪唑 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以74%的产率得到2,5-cis-dicyanopyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  cis-2,5-Dicyanopyrrolidine Inhibitors of Dipeptidyl Peptidase IV:  Synthesis and in Vitro, in Vivo, and X-ray Crystallographic Characterization

  摘要：

  Inhibitors of the glucagon-like peptide-1 (GLP-1) degrading enzyme dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes in animal models and in human subjects. A novel series of cis-2,5-dicyanopyrrolidine alpha-amino amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. 1-({[1-(Hydroxymethyl) cyclopentyl] amino}acetyl) pyrrolidine-2,5-cis-dicarbonitrile (1c) is an achiral, slow-binding (time-dependent) inhibitor of DPP-IV that is selective for DPP-IV over other DPP isozymes and proline specific serine proteases, and which has oral bioavailability in preclinical species and in vivo efficacy in animal models. The mode of binding of the cis-2,5-dicyanopyrrolidine moiety was determined by X-ray crystallography. The hydrochloride salt of 1c was further profiled for development as a potential new treatment for type 2 diabetes.

  DOI：

  10.1021/jm0600085
• 作为产物：
  描述：

  diethyl meso-2,5-dibromoadipate 在 ammonium hydroxide 、 氨 、 氢气 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 20.0~80.0 ℃ 、344.74 kPa 条件下， 反应 220.0h， 生成 2,5-cis-dicarbamoylpyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  cis-2,5-Dicyanopyrrolidine Inhibitors of Dipeptidyl Peptidase IV:  Synthesis and in Vitro, in Vivo, and X-ray Crystallographic Characterization

  摘要：

  Inhibitors of the glucagon-like peptide-1 (GLP-1) degrading enzyme dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes in animal models and in human subjects. A novel series of cis-2,5-dicyanopyrrolidine alpha-amino amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. 1-({[1-(Hydroxymethyl) cyclopentyl] amino}acetyl) pyrrolidine-2,5-cis-dicarbonitrile (1c) is an achiral, slow-binding (time-dependent) inhibitor of DPP-IV that is selective for DPP-IV over other DPP isozymes and proline specific serine proteases, and which has oral bioavailability in preclinical species and in vivo efficacy in animal models. The mode of binding of the cis-2,5-dicyanopyrrolidine moiety was determined by X-ray crystallography. The hydrochloride salt of 1c was further profiled for development as a potential new treatment for type 2 diabetes.

  DOI：

  10.1021/jm0600085

文献信息

• Synthetic studies on the thiostrepton family of peptide antibiotics: synthesis of the tetrasubstituted dehydropiperidine and piperidine cores
  作者：Syuhei Higashibayashi、Kimiko Hashimoto、Masaya Nakata

  DOI：10.1016/s0040-4039(01)02090-1

  日期：2002.1

  The tetrasubstituted dehydropiperidine and piperidine cores of the thiostrepton family of peptide antibiotics were synthesized which featured the coupling between the azomethine ylide and the enantiopure sulfinimine, and the subsequent stereoselective reduction of the six-membered imine.

  合成了肽抗生素的硫代链霉菌素家族的四取代的脱氢哌啶和哌啶核心，其特征在于偶氮甲碱内酯和对映体亚磺酰胺之间的偶联，以及随后的六元亚胺的立体选择性还原。