1-Piperidinecarboxylic acid, 2-methyl-,1-[(4-cyanophenyl)methyl]-2-[(1,1-dimethylethoxy)carbonyl]hydrazide | 390747-69-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-Piperidinecarboxylic acid, 2-methyl-,1-[(4-cyanophenyl)methyl]-2-[(1,1-dimethylethoxy)carbonyl]hydrazide
• 英文别名: tert-butyl 2-(4-cyanobenzyl)-2-[(2-methyl-1-piperidinyl)carbonyl]hydrazine carboxylate
• CAS: 390747-69-0
• 化学式: C₂₀H₂₈N₄O₃
• 分子量: 372.467
• InChiKey: RITOHHGDFGVHEU-UHFFFAOYSA-N

物化性质

• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.79
• 重原子数：
  27.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  85.67
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-Piperidinecarboxylic acid, 2-methyl-,1-[(4-cyanophenyl)methyl]-2-[(1,1-dimethylethoxy)carbonyl]hydrazide 在 盐酸 、 ammonium acetate 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Thrombin inhibitors built on an azaphenylalanine scaffold

  摘要：

  A series of azaphenylalanine derivatives were investigated as novel thrombin inhibitors based on the prodrug principle. By systematic structural modifications we have identified optimal groups for this series that led us to potent inhibitors of thrombin incorporating the benzamidine fragment at the PI position, and their potentially orally active benzamidoxime prodrugs. The binding modes in the thrombin active site of two representative compounds were identified by X-ray crystallographic analysis. (C) 2004 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2003.12.083
• 作为产物：
  描述：

  4-氰基苯甲醛 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 生成 1-Piperidinecarboxylic acid, 2-methyl-,1-[(4-cyanophenyl)methyl]-2-[(1,1-dimethylethoxy)carbonyl]hydrazide
  参考文献：
  名称：

  Thrombin inhibitors built on an azaphenylalanine scaffold

  摘要：

  A series of azaphenylalanine derivatives were investigated as novel thrombin inhibitors based on the prodrug principle. By systematic structural modifications we have identified optimal groups for this series that led us to potent inhibitors of thrombin incorporating the benzamidine fragment at the PI position, and their potentially orally active benzamidoxime prodrugs. The binding modes in the thrombin active site of two representative compounds were identified by X-ray crystallographic analysis. (C) 2004 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2003.12.083

文献信息

• Design and structure–activity relationship of thrombin inhibitors with an azaphenylalanine scaffold: potency and selectivity enhancements via P2 optimization
  作者：A Zega、G Mlinšek、P Šepic、S Golič Grdadolnik、T Šolmajer、T.B Tschopp、B Steiner、D Kikelj、U Urleb

  DOI：10.1016/s0968-0896(01)00202-4

  日期：2001.10

  provides an enhanced fit into this active site S2 pocket. In the present paper, we also report on the structure of these inhibitors in solution and conformational analysis of inhibitors in the active site in order to asses the consequences of the replacement of the central alpha-CH by a nitrogen functionality. In vitro biological testing of the designed inhibitors shows that elimination of R, S stereoisomerism

  理论和结构研究，然后进行定向合成和体外生物学测试，使我们获得了新型的非共价凝血酶假肽抑制剂。我们已经将氮杂肽支架整合到经典三肽D-Phe-Pro-Arg抑制剂结构的中心部分，从而从分子中消除了一个立体定位中心。设计了一系列化合物以优化凝血酶S2口袋的占用率。在P2处增加的疏水性增强了对该活性位点S2口袋的贴合性。在本文中，我们还报告了这些抑制剂在溶液中的结构以及活性位点中抑制剂的构象分析，以评估氮官能团取代中心α-CH的后果。