(S)-tert-butyl 2-(2-propynyloxymethyl)pyrrolidine-1-carboxylate | 1092522-52-5

• 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: (S)-tert-butyl 2-(2-propynyloxymethyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (S)-2-((prop-2-yn-1-yloxy)methyl)pyrrolidine-1-carboxylate；tert-butyl (2S)-2-[(prop-2-yn-1-yloxy)methyl]pyrrolidine-1-carboxylate；(S)-tert-butyl-2-((prop-2-yn-1-yloxy)methyl)pyrrolidine-1-carboxylate；tert-butyl (2S)-2-(prop-2-ynoxymethyl)pyrrolidine-1-carboxylate
• CAS: 1092522-52-5
• 化学式: C₁₃H₂₁NO₃
• 分子量: 239.315
• InChiKey: RJWPQSXRDPYTPZ-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 2-(2-propynyloxymethyl)pyrrolidine-1-carboxylate 在 chromium(VI) oxide 、 copper(ll) sulfate pentahydrate 、 叔丁基锂 、 溶剂黄146 、 sodium ascorbate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 正戊烷 为溶剂， 反应 6.67h， 生成 (S)-5-((2-(((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methoxy)methyl)pyrrolidin-1-yl)sulfonyl)-1-propyl-1H-pyrrolo[2,3-b]pyridine-2,3-dione
  参考文献：
  名称：

  Novel fluorine-18 labeled 5-(1-pyrrolidinylsulfonyl)-7-azaisatin derivatives as potential PET tracers for in vivo imaging of activated caspases in apoptosis

  摘要：

  The programmed type I cell death, defined as apoptosis, is induced by complex regulated signaling pathways that trigger the intracellular activation of executioner caspases-3, -6 and -7. Once activated, these enzymes initiate cellular death through cleavage of proteins which are responsible for DNA repair, signaling and cell maintenance. Several radiofluorinated inhibitors of caspases-3 and -7, comprising a moderate lipophilic 5-(1-pyrrolidinylsulfonyl)isatin lead structure, are currently being investigated for imaging apoptosis in vivo by us and others. The purpose of this study was to increase the intrinsic hydrophilicity of the aforementioned lead structure to alter the pharmacokinetic behavior of the resulting caspase-3 and -7 targeted radiotracer. Therefore, fluorinated and non-fluorinated derivatives of 5-(1-pyrrolidinylsulfonyl)-7-azaisatin were synthesized and tested for their inhibitory properties against recombinant caspases-3 and -7. Fluorine-18 has been introduced by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of an alkyne precursor with 2-[F-18]fluoroethylazide. Using dynamic micro-PET biodistribution studies in vivo the kinetic behavior of one promising PET-compatible 5-pyrrolidinylsulfonyl 7-azaisatin derivative has been compared to a previously described isatin based radiotracer. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.014
• 作为产物：
  描述：

  N-Boc-L-脯氨醇 、 3-溴丙炔 在 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 以88%的产率得到(S)-tert-butyl 2-(2-propynyloxymethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  基于 (2S)-(1,2,4-Triazol-3-yl)-Proline 的新型介孔二氧化硅负载有机催化剂：用于不对称醛醇反应的高效、可重复使用和多相催化剂

  摘要：

  基于最近开发的 (S)-脯氨酸衍生物 (2S)-[5-(苄基硫基)-4-苯基-(1,2,4-三唑)-3-基]-吡咯烷负载在介孔二氧化硅上的新型有机催化系统是制备并在不对称醛醇反应中评估它们的效率。这些材料通过 FT-IR、MS、XRD 和 SEM 显微镜进行了全面表征，收集了有关掺杂二氧化硅中的组成、形态和有机催化剂分布的相关信息。仔细优化它们在酮和醛之间的不对称醛醇反应中用作催化剂所需的反应条件，提供了预期的醛醇产物，具有优异的产率和适中的非对映选择性和对映选择性。推荐的实验方案简单、快速、高效，提供对映体富集的醛醇产品，通常不需要特殊的后处理或纯化方案。这种方法构成了基于异质（S）-脯氨酸的有机催化领域的显着改进；特别地，本文所述的固相二氧化硅键合催化系统允许显着减少溶剂使用。此外，与新合成的有机催化剂相比，此处描述的支撑系统可以回收、重新激活和重复使用多次，催化效率损失有限。

  DOI：

  10.3390/molecules25194532

文献信息

• PYRIDAZINONES AS PARP7 INHIBITORS
  申请人：Ribon Therapeutics Inc.

  公开号：US20190330194A1

  公开（公告）日：2019-10-31

  The present invention relates to pyridazinones and related compounds which are inhibitors of PARP7 and are useful in the treatment of cancer.

  本发明涉及吡啶并嗪酮和相关化合物，它们是PARP7的抑制剂，并且在癌症治疗中很有用。
• ISATIN DERIVATIVES FOR USE AS IN VIVO IMAGING AGENTS
  申请人：Aboabye Eric Ofori

  公开号：US20110195024A1

  公开（公告）日：2011-08-11

  Isatin 5-sulfonamide derivatives, pharmaceutical compositions comprising the derivatives, their use as molecular imaging agents, their use for the diagnosis or treatment of diseases or disorders associated with dysregulation of apoptosis, methods for synthesizing the derivatives, methods for the molecular imaging of caspase activity and apoptosis, and methods of assessing the therapeutic effect of a test substance on caspase activity are disclosed.

  本发明公开了Isatin 5-磺酰胺衍生物，包括该衍生物的制药组合物，其作为分子成像剂的用途，其用于诊断或治疗与凋亡失调相关的疾病或障碍的用途，制备该衍生物的方法，评估试验物质对caspase活性的治疗效果的方法，以及评估凋亡的分子成像和caspase活性的方法。
• Isatin derivatives for use as in vivo imaging agents
  申请人：Aboagye Eric Ofori

  公开号：US08961930B2

  公开（公告）日：2015-02-24

  Isatin 5-sulfonamide derivatives, pharmaceutical compositions comprising the derivatives, their use as molecular imaging agents, their use for the diagnosis or treatment of diseases or disorders associated with dysregulation of apoptosis, methods for synthesizing the derivatives, methods for the molecular imaging of caspase activity and apoptosis, and methods of assessing the therapeutic effect of a test substance on caspase activity are disclosed.

  本发明公开了5-磺酰胺基异喹啉衍生物、包含该衍生物的制药组合物、其作为分子成像剂的应用、其用于诊断或治疗与细胞凋亡失调相关的疾病或疾病的方法、合成该衍生物的方法、测定caspase活性和细胞凋亡的分子成像方法以及评估测试物质对caspase活性的治疗效果的方法。
• Design, Synthesis, and Biological Characterization of a Caspase 3/7 Selective Isatin Labeled with 2-[¹⁸F]fluoroethylazide
  作者：Graham Smith、Matthias Glaser、Meg Perumal、Quang-De Nguyen、Bo Shan、Erik Årstad、Eric O. Aboagye

  DOI：10.1021/jm801107u

  日期：2008.12.25

  Imaging of programmed cell death (apoptosis) is important in the assessment of therapeutic response in oncology and for diagnosis in cardiac and neurodegenerative disorders. The executioner caspases 3 and 7 ultimately effect cellular death, thus providing selective molecular targets for in vivo quantification of apoptosis. To realize this potential, we aimed to develop F-18-labeled isatin sulfonamides with high metabolic,stability and moderate lipophilicity while retaining selectivity and affinity for caspase 3/7. A small library of isatins modified with fluorinated aromatic groups and heterocycles was synthesized. A lead compound incorporating 2'-fluoroethyl-1,2,3-triazole was identified with subnanomolar affinity for caspase 3. "Click labeling" provided the F-18-labeled tracer in 65 +/- 6% decay-corrected radiochemical yield from 2-[F-18]fluoroethylazide. The compound showed high stability in vivo with rapid uptake and elimination in healthy tissues and tumor. The novel F-18-labeled isatin is a candidate radiotracer for further preclinical evaluation for imaging of apoptosis.
• JP5667056
  申请人：——

  公开号：——

  公开（公告）日：——