tert-butyl (3R)-3-(2-fluoroethoxy)pyrrolidine-1-carboxylate | 864758-06-5

• 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 (3R)-3-(2-fluoroethoxy)pyrrolidine-1-carboxylate
• CAS: 864758-06-5
• 化学式: C₁₁H₂₀FNO₃
• 分子量: 233.283
• InChiKey: QSURQMNDGQWNQC-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (3R)-3-(2-fluoroethoxy)pyrrolidine-1-carboxylate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 (R)-4-(4-fluoro-3-(3-(2-fluoroethoxy)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one
  参考文献：
  名称：

  Synthesis and evaluation of an AZD2461 [18F]PET probe in non-human primates reveals the PARP-1 inhibitor to be non-blood-brain barrier penetrant

  摘要：

  Poly(ADP-ribose)polymerase-1 inhibitor (PARPi) AZD2461 was designed to be a weak P-glycoprotein (P-gp) analogue of FDA approved olaparib. With this chemical property in mind, we utilized the AZD2461 ligand architecture to develop a CNS penetrant and PARP-1 selective imaging probe, in order to investigate PARP-1 mediated neuroinflammation and neurodegenerative diseases, such as Alzheimer's and Parkinson's. Our work led to the identification of several high-affinity PARPi, including AZD2461 congener 9e (PARP-1 IC50, = 3.9 +/- 1.2 nM), which was further evaluated as a potential F-18-PET brain imaging probe. However, despite the similar molecular scaffolds of 9e and AZD2461, our studies revealed non-appreciable brain-uptake of [F-18]9e in non-human primates, suggesting AZD2461 to be non-CNS penetrant.

  DOI：

  10.1016/j.bioorg.2018.10.015
• 作为产物：
  描述：

  对甲苯磺酸氟乙酯 、 (R)-1-Boc-3-羟基吡咯烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 tert-butyl (3R)-3-(2-fluoroethoxy)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis and evaluation of an AZD2461 [18F]PET probe in non-human primates reveals the PARP-1 inhibitor to be non-blood-brain barrier penetrant

  摘要：

  Poly(ADP-ribose)polymerase-1 inhibitor (PARPi) AZD2461 was designed to be a weak P-glycoprotein (P-gp) analogue of FDA approved olaparib. With this chemical property in mind, we utilized the AZD2461 ligand architecture to develop a CNS penetrant and PARP-1 selective imaging probe, in order to investigate PARP-1 mediated neuroinflammation and neurodegenerative diseases, such as Alzheimer's and Parkinson's. Our work led to the identification of several high-affinity PARPi, including AZD2461 congener 9e (PARP-1 IC50, = 3.9 +/- 1.2 nM), which was further evaluated as a potential F-18-PET brain imaging probe. However, despite the similar molecular scaffolds of 9e and AZD2461, our studies revealed non-appreciable brain-uptake of [F-18]9e in non-human primates, suggesting AZD2461 to be non-CNS penetrant.

  DOI：

  10.1016/j.bioorg.2018.10.015

文献信息

• Pyridone derivative
  申请人：Otake Norikazu

  公开号：US20070208046A1

  公开（公告）日：2007-09-06

  The invention provides pyridone derivatives represented by a general formula (I) [in the formula, R 1 and R 2 may be same or different and stands for H, etc., or R 1 and R 2 may form an aliphatic nitrogen-containing heterocyclic group together with the N to which they bind; X 1 -X 3 may be same or different and stand for methine or N, provided not all of them simultaneously stand for nitrogen; X 4 -X 7 may be same or different and stand for methine or N, provided that three or more of them do not simultaneously stand for N; Y 1 and Y 3 may be same or different and stand for single bond, —O—, —NR—, —S—, etc; Y 2 stands for lower alkylene, etc.; R stands for H, etc., L stands for methylene; Z 1 and Z 2 may be same or different and stand for single bond or lower alkylene; or R 1 , L and Z 2 may form an aliphatic nitrogen-containing heterocyclic group with the N to which R 1 binds; and Ar stands for aromatic carbocyclic group, etc.].

  该发明提供了由通式（I）表示的吡啶酮衍生物[在公式中，R1和R2可能相同或不同，代表H等，或者R1和R2可能与它们结合的N一起形成一个脂肪族含氮杂环基团；X1-X3可能相同或不同，代表亚甲或N，但不能同时都代表氮；X4-X7可能相同或不同，代表亚甲或N，但不能同时有三个或更多同时代表N；Y1和Y3可能相同或不同，代表单键，-O-，-NR-，-S-等；Y2代表较低的烷基等；R代表H等，L代表亚甲基；Z1和Z2可能相同或不同，代表单键或较低的烷基；或者R1、L和Z2可能与R1结合的N一起形成一个脂肪族含氮杂环基团；Ar代表芳香族碳环基团等]。
• EP1741703
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and evaluation of an AZD2461 [18F]PET probe in non-human primates reveals the PARP-1 inhibitor to be non-blood-brain barrier penetrant
  作者：Sean W. Reilly、Laura N. Puentes、Alexander Schmitz、Chia-Ju Hsieh、Chi-Chang Weng、Catherine Hou、Shihong Li、Yin-Ming Kuo、Prashanth Padakanti、Hsiaoju Lee、Aladdin A. Riad、Mehran Makvandi、Robert H. Mach

  DOI：10.1016/j.bioorg.2018.10.015

  日期：2019.3

  Poly(ADP-ribose)polymerase-1 inhibitor (PARPi) AZD2461 was designed to be a weak P-glycoprotein (P-gp) analogue of FDA approved olaparib. With this chemical property in mind, we utilized the AZD2461 ligand architecture to develop a CNS penetrant and PARP-1 selective imaging probe, in order to investigate PARP-1 mediated neuroinflammation and neurodegenerative diseases, such as Alzheimer's and Parkinson's. Our work led to the identification of several high-affinity PARPi, including AZD2461 congener 9e (PARP-1 IC50, = 3.9 +/- 1.2 nM), which was further evaluated as a potential F-18-PET brain imaging probe. However, despite the similar molecular scaffolds of 9e and AZD2461, our studies revealed non-appreciable brain-uptake of [F-18]9e in non-human primates, suggesting AZD2461 to be non-CNS penetrant.