2-(2-furyl)pyrrolidine | 1039033-91-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-(2-furyl)pyrrolidine
• 英文别名: (R)-2-(2-furyl)pyrrolidine；(2R)-2-(furan-2-yl)pyrrolidine
• CAS: 1039033-91-4
• 化学式: C₈H₁₁NO
• 分子量: 137.181
• InChiKey: LIFJPSLQRGQNMM-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  25.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(2-furyl)pyrrolidine 、 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以14%的产率得到N-[3-[[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]amino]phenyl]-7-[(2R)-2-(furan-2-yl)pyrrolidin-1-yl]-7-oxoheptanamide
  参考文献：
  名称：

  Discovery of Bivalent Kinase Inhibitors via Enzyme-Templated Fragment Elaboration

  摘要：

  We have employed novel fragment-based screening methodology to discover bivalent kinase inhibitors with improved selectivity. Starting from a low molecular weight promiscuous kinase inhibitor, we appended a thiol for subsequent reaction with a library of acrylamide electrophiles. Enzyme-templated screening was performed to identify acrylamides that assemble into bivalent inhibitors of c-Src kinase. Upon identification of acrylamide fragments that improve the binding affinity of our lead thiol, we characterized the resulting bivalent inhibitors and identified a series of kinase inhibitors with improved potency and selectivity compared to the thiol-containing precursor. Provided that protein can be prepared free of endogenous reactive cysteines, our methodology is general and could be applied to nearly any enzyme of interest.

  DOI：

  10.1021/acsmedchemlett.5b00167
• 作为产物：
  描述：

  (S)-N-(furan-2-ylmethylene)-2-methylpropane-2-sulfinamide 在 盐酸 、 sodium cyanoborohydride 、 magnesium 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 32.0h， 生成 2-(2-furyl)pyrrolidine
  参考文献：
  名称：

  Discovery of Bivalent Kinase Inhibitors via Enzyme-Templated Fragment Elaboration

  摘要：

  We have employed novel fragment-based screening methodology to discover bivalent kinase inhibitors with improved selectivity. Starting from a low molecular weight promiscuous kinase inhibitor, we appended a thiol for subsequent reaction with a library of acrylamide electrophiles. Enzyme-templated screening was performed to identify acrylamides that assemble into bivalent inhibitors of c-Src kinase. Upon identification of acrylamide fragments that improve the binding affinity of our lead thiol, we characterized the resulting bivalent inhibitors and identified a series of kinase inhibitors with improved potency and selectivity compared to the thiol-containing precursor. Provided that protein can be prepared free of endogenous reactive cysteines, our methodology is general and could be applied to nearly any enzyme of interest.

  DOI：

  10.1021/acsmedchemlett.5b00167

文献信息

• Synthesis and Pharmacological Characterization of Chiral Pyrrolidinylfuran Derivatives: The Discovery of New Functionally Selective Muscarinic Agonists
  作者：Serena Scapecchi、Marta Nesi、Rosanna Matucci、Cristina Bellucci、Michela Buccioni、Silvia Dei、Luca Guandalini、Dina Manetti、Elisabetta Martini、Gabriella Marucci、Maria Novella Romanelli、Elisabetta Teodori、Roberto Cirilli

  DOI：10.1021/jm800145d

  日期：2008.7

  further characterizing subtypes of cholinergic receptors. Unlike their parent compounds, the new molecules lack nicotinic activity, being pure muscarinic ligands. While binding studies on the five cloned human muscarinic receptors showed no subtype selectivity, functional assays revealed that some of the molecules of the series are potent M 2 selective partial agonists with interesting pharmacological

  基于先前成功应用的假设，即胆碱能激动剂关键阳离子头附近的立体化学复杂化将导致亚型选择性化合物，我们合成了一系列呋喃酯和5-甲基呋喃酯的手性衍生物，目的是获得化合物可用于治疗源自胆碱能受体功能障碍的疾病和/或用于进一步表征胆碱能受体亚型的药物。与它们的母体化合物不同，新分子缺乏烟碱活性，是纯毒蕈碱配体。虽然对五个克隆的人毒蕈碱受体的结合研究没有显示亚型的选择性，但功能分析表明，该系列中的某些分子是具有有趣药理学特征的强效M 2选择性部分激动剂。
• Discovery of Bivalent Kinase Inhibitors via Enzyme-Templated Fragment Elaboration
  作者：Frank E. Kwarcinski、Michael E. Steffey、Christel C. Fox、Matthew B. Soellner

  DOI：10.1021/acsmedchemlett.5b00167

  日期：2015.8.13

  We have employed novel fragment-based screening methodology to discover bivalent kinase inhibitors with improved selectivity. Starting from a low molecular weight promiscuous kinase inhibitor, we appended a thiol for subsequent reaction with a library of acrylamide electrophiles. Enzyme-templated screening was performed to identify acrylamides that assemble into bivalent inhibitors of c-Src kinase. Upon identification of acrylamide fragments that improve the binding affinity of our lead thiol, we characterized the resulting bivalent inhibitors and identified a series of kinase inhibitors with improved potency and selectivity compared to the thiol-containing precursor. Provided that protein can be prepared free of endogenous reactive cysteines, our methodology is general and could be applied to nearly any enzyme of interest.