tert-butyl (4-(3,4-dimethoxyphenyl)pyrrolidin-3-yl)carbamate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl (4-(3,4-dimethoxyphenyl)pyrrolidin-3-yl)carbamate
• 英文别名: tert-butyl N-[(3S,4R)-4-(3,4-dimethoxyphenyl)pyrrolidin-3-yl]carbamate
• 化学式: C₁₇H₂₆N₂O₄
• 分子量: 322.404
• InChiKey: LLPLOJAMKAESKJ-QWHCGFSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  68.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-(3,4-dimethoxyphenyl)pyrrolidin-3-yl)carbamate 在 盐酸 、 sodium cyanoborohydride 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Are We There Yet? Applying Thermodynamic and Kinetic Profiling on Embryonic Ectoderm Development (EED) Hit-to-Lead Program

  摘要：

  It is advocated that kinetic and thermodynamic profiling of bioactive compounds should be incorporated and utilized as complementary tools for hit and lead optimizations in drug discovery. To assess their applications in the EED hit-to-lead optimization process, large amount of thermodynamic and kinetic data were collected and analyzed via isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR), respectively. Slower dissociation rates (k(off)) of the lead compounds were observed as the program progressed. Analysis of the kinetic data indicated that compound cellular activity correlated with both K-i; and k(off). Our analysis revealed that ITC data should be interpreted in the context of chiral purity of the compounds. The thermodynamic signatures of the EED aminopyrrolidine compounds were found to be mainly enthalpy driven with improved enthalpic contributions as the program progressed. Our study also demonstrated that significant challenges still exist in utilizing kinetic and thermodynamic parameters for hit selection.

  DOI：

  10.1021/acs.jmedchem.7b00576
• 作为产物：
  描述：

  tert-butyl (1-benzyl-4-(3,4-dimethoxyphenyl)pyrrolidin-3-yl)carbamate 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 25.0 ℃ 、103.42 kPa 条件下， 反应 24.0h， 以86%的产率得到tert-butyl (4-(3,4-dimethoxyphenyl)pyrrolidin-3-yl)carbamate
  参考文献：
  名称：

  Are We There Yet? Applying Thermodynamic and Kinetic Profiling on Embryonic Ectoderm Development (EED) Hit-to-Lead Program

  摘要：

  It is advocated that kinetic and thermodynamic profiling of bioactive compounds should be incorporated and utilized as complementary tools for hit and lead optimizations in drug discovery. To assess their applications in the EED hit-to-lead optimization process, large amount of thermodynamic and kinetic data were collected and analyzed via isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR), respectively. Slower dissociation rates (k(off)) of the lead compounds were observed as the program progressed. Analysis of the kinetic data indicated that compound cellular activity correlated with both K-i; and k(off). Our analysis revealed that ITC data should be interpreted in the context of chiral purity of the compounds. The thermodynamic signatures of the EED aminopyrrolidine compounds were found to be mainly enthalpy driven with improved enthalpic contributions as the program progressed. Our study also demonstrated that significant challenges still exist in utilizing kinetic and thermodynamic parameters for hit selection.

  DOI：

  10.1021/acs.jmedchem.7b00576

文献信息

• Are We There Yet? Applying Thermodynamic and Kinetic Profiling on Embryonic Ectoderm Development (EED) Hit-to-Lead Program
  作者：Ying Wang、Rohinton P. Edalji、Sanjay C. Panchal、Chaohong Sun、Stevan W. Djuric、Anil Vasudevan

  DOI：10.1021/acs.jmedchem.7b00576

  日期：2017.10.26

  It is advocated that kinetic and thermodynamic profiling of bioactive compounds should be incorporated and utilized as complementary tools for hit and lead optimizations in drug discovery. To assess their applications in the EED hit-to-lead optimization process, large amount of thermodynamic and kinetic data were collected and analyzed via isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR), respectively. Slower dissociation rates (k(off)) of the lead compounds were observed as the program progressed. Analysis of the kinetic data indicated that compound cellular activity correlated with both K-i; and k(off). Our analysis revealed that ITC data should be interpreted in the context of chiral purity of the compounds. The thermodynamic signatures of the EED aminopyrrolidine compounds were found to be mainly enthalpy driven with improved enthalpic contributions as the program progressed. Our study also demonstrated that significant challenges still exist in utilizing kinetic and thermodynamic parameters for hit selection.