(3aS,8aR)-3-[prop-2-yn-1-yl]-3,3a,8,8a-tetrahydroindeno[1,2-d][1,2,3]oxathiazole 2,2-dioxide | 1146973-09-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (3aS,8aR)-3-[prop-2-yn-1-yl]-3,3a,8,8a-tetrahydroindeno[1,2-d][1,2,3]oxathiazole 2,2-dioxide
• 英文别名: (3aS,8aR)-3-(prop-2-yn-1-yl)-3,3a,8,8a-tetrahydroindeno[1,2-d][1,2,3]oxathiazole 2,2-dioxide；(3aR,8bS)-1-prop-2-ynyl-4,8b-dihydro-3aH-indeno[1,2-d]oxathiazole 2,2-dioxide
• CAS: 1146973-09-2
• 化学式: C₁₂H₁₁NO₃S
• 分子量: 249.29
• InChiKey: SISGTSXVMIDKEJ-NEPJUHHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3aS,8aR)-3-[prop-2-yn-1-yl]-3,3a,8,8a-tetrahydroindeno[1,2-d][1,2,3]oxathiazole 2,2-dioxide 在 [18F]-tetrabutylammonium fluoride 、 硫酸 作用下， 以 二甲基亚砜 、 水 、 乙腈 为溶剂， 反应 0.04h， 生成 (1S,2S)-2-[(18)F]-fluoro-N-(prop-2-yn-1-yl)-indan-1-amine
  参考文献：
  名称：

  [EN] COMPOUNDS FOR USE IN IMAGING, DIAGNOSING, AND/OR TREATMENT OF DISEASES OF THE CENTRAL NERVOUS SYSTEM OR OF TUMORS
  [FR] COMPOSÉS DESTINÉS À ÊTRE UTILISÉS DANS LE CADRE D'IMAGERIE, DE DIAGNOSTIC ET/OU DE TRAITEMENT DE MALADIES DU SYSTÈME NERVEUX CENTRAL OU DE TUMEURS

  摘要：

  公开号：

  WO2009052970A3
• 作为产物：
  描述：

  (1S,2R)-(-)-1-氨基-2-茚醇 在 磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 (3aS,8aR)-3-[prop-2-yn-1-yl]-3,3a,8,8a-tetrahydroindeno[1,2-d][1,2,3]oxathiazole 2,2-dioxide
  参考文献：
  名称：

  Synthesis and evaluation of [18F]fluororasagiline, a novel positron emission tomography (PET) radioligand for monoamine oxidase B (MAO-B)

  摘要：

  The aim of this study was to synthesize and evaluate a novel fluorine-18 labeled analogue of rasagiline (6) as a PET radioligand for monoamine oxidase B (MAO-B). The corresponding non-radioactive fluorine-19 ligand, (1S,2S)-2-fluoro-N-(prop-2-yn-1-yl)indan-1-amine (4), was characterized in in vitro assays.The precursor compound (3aS,8aR)-3-(prop-2-yn-1-yl)-3,3a,8,8a-tetrahydroindeno[1,2-d][1,2,3]oxa-thiazole 2,2-dioxide (3) and reference standard 4 were synthesized in multi-step syntheses. Recombinant human MAO-B and MAO-A enzyme preparations were used in order to determine IC50 values for compound 4 by use of an enzymatic assay employing kynuramine as substrate. Radiolabeling was accomplished by a two-step synthesis, compromising a nucleophilic substitution followed by hydrolysis of the sulphamidate group. Human whole hemisphere autoradiography (ARG) was performed with [F-18]fluororasagiline. Blocking experiments with pirlindole (MAO-A), L-deprenyl and rasagiline (MAO-B) were conducted to demonstrate the specificity of the binding. A positron emission tomography (PET) study was carried out in a cynomolgus monkey where time activity curves for whole brain and regions with high and low MAO-B activity were recorded. Radiometabolites were measured in monkey plasma using gradient HPLC.Compound 4 inhibited MAO-B with an IC50 of 27 nM and MAO-A with an IC50 of 2.3 mu M. Radiolabeling of precursor 3 and subsequent hydrolysis of the protecting group towards (1S,2S)-2-[F-18]fluoro-N-(prop-2-yn-1-yl)indan-1-amine (6) was successfully accomplished with an radiochemical yield of 40-70%, a radiochemical purity higher than 99% and a specific radioactivity higher than 200 GBq/mu mol. ARG demonstrated selective binding for [F-18]fluororasagiline (6) to MAO-B containing brain regions, for example, striatum. The initial uptake in the monkey brain was 250% SUV at 4 min post injection. The highest amounts of radioactivity were observed in the striatum and thalamus as expected whereas in the cortex and cerebellum lower levels were observed. Metabolite studies demonstrated 30% unchanged radioligand at 90 min post injection.Our investigations demonstrated that the new ligand [F-18]fluororasagiline (6) binds specifically to MAO-B in vitro and has a MAO-B specific binding pattern in vivo. Thus, it could serve as a novel potential candidate for human PET studies. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.056

文献信息

• COMPOUNDS FOR USE IN IMAGING, DIAGNOSING AND/OR TREATMENT OF DISEASES OF THE CENTRAL NERVOUS SYSTEM OR OF TUMORS
  申请人：Lehmann Lutz

  公开号：US20100233086A1

  公开（公告）日：2010-09-16

  This invention relates to novel compounds suitable for labelling or already labelled by 18 F, methods of preparing such a compound, compositions comprising such compounds, kits comprising such compounds or compositions and uses of such compounds, compositions or kits for diagnostic imaging by positron emission tomography (PET).

  本发明涉及适用于标记或已经通过18F标记的新型化合物，制备这种化合物的方法，包含这种化合物的组合物，包含这种化合物或组合物的试剂盒以及这种化合物，组合物或试剂盒用于正电子发射断层摄影（PET）的诊断成像的用途。
• Compounds for use in imaging, diagnosing and/or treatment of diseases of the central nervous system or of tumors
  申请人：Lehmann Lutz

  公开号：US08784775B2

  公开（公告）日：2014-07-22

  This invention relates to novel compounds suitable for labeling or already labeled by 18F, methods of preparing such a compound, compositions comprising such compounds, kits comprising such compounds or compositions and uses of such compounds, compositions or kits for diagnostic imaging by positron emission tomography (PET).

  本发明涉及一种新型化合物，适用于标记或已经用18F标记，制备此类化合物的方法，包含此类化合物的组合物，包含此类化合物或组合物的工具箱以及此类化合物、组合物或工具箱用于正电子发射断层摄影（PET）诊断成像的用途。
• COMPOUNDS FOR USE IN IMAGING, DIAGNOSING, AND/OR TREATMENT OF DISEASES OF THE CENTRAL NERVOUS SYSTEM OR OF TUMORS
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP2217549A2

  公开（公告）日：2010-08-18
• US8784775B2
  申请人：——

  公开号：US8784775B2

  公开（公告）日：2014-07-22
• US9682944B2
  申请人：——

  公开号：US9682944B2

  公开（公告）日：2017-06-20