2a-[4-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)butyl]-2a,3,4,5-tetrahydro-1H-benz[cd]indol-2-one | 230301-31-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2a-[4-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)butyl]-2a,3,4,5-tetrahydro-1H-benz[cd]indol-2-one
• 英文别名: 2a-[4-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)butyl]-2a,3,4,5-tetrahydro-1H-benz[cd]indole-2-one；2a-(4-(4,5,6,7-Tetrahydro-thieno[3,2-c]pyridin-5-yl)butyl)-2a,3,4,5-tetrahydro-1H-benz[cd]indol-2-one；2a-[4-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)butyl]-1,3,4,5-tetrahydrobenzo[cd]indol-2-one
• CAS: 230301-31-2
• 化学式: C₂₂H₂₆N₂OS
• 分子量: 366.527
• InChiKey: PSWCYJDXBLJOMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  60.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [11C]methyl iodide 、 2a-[4-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)butyl]-2a,3,4,5-tetrahydro-1H-benz[cd]indol-2-one 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 生成 2a-[4-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)butyl]-1-(111C)methyl-4,5-dihydro-3H-benzo[cd]indol-2-one
  参考文献：
  名称：

  Synthesis and preliminary PET study of the 5-HT7 receptor antagonist [11C]DR4446

  摘要：

  DR4446 （1-甲基-2a-[4-(4,5,6,7-四氢噻吩并[3,2-c]吡啶-5-基)丁基]-2a,3,4,5-四氢-1H-苯并[cd]吲哚-2-酮）是一种强效的 5-HT7 受体拮抗剂（Ki=9.7 nM），对其他 5-HT 家族受体具有高选择性（对 5-HT1A 的 Ki：770 nM；对其他 5-HT 受体的 Ki：>1000 nM）。作为 5-HT7 受体的正电子发射断层扫描（PET）示踪剂，[11C]DR4446 是在 NaH 存在下用[11C]CH3I 对去甲基前体（1）进行烷基化合成的，具有很高的放射化学纯度（>98%），合成结束时的比活度为 73-120 GBq/μmol。对猴子进行的 PET 研究表明，[11C]DR4446 在大脑中具有良好的渗透性，并在包括丘脑在内的脑区（可能是 5-HT7 受体区域）具有特异性结合成分。代谢物分析表明，[11C]DR4446相对稳定，使用高效液相色谱法在猴子血浆中检测到了低百分比的两种放射性标记代谢物。Copyright © 2002 John Wiley & Sons, Ltd. All Rights Reserved.

  DOI：

  10.1002/jlcr.606
• 作为产物：
  描述：

  4,5,6,7-四氢噻吩[3,2-C]吡啶-2-羧酸 在 氢溴酸 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2a-[4-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)butyl]-2a,3,4,5-tetrahydro-1H-benz[cd]indol-2-one
  参考文献：
  名称：

  Tetrahydrothienopyridylbutyl-tetrahydrobenzindoles: New Selective Ligands of the 5-HT7 Receptor

  摘要：

  The synthesis and the affinity for the 5-HT7 receptor and other receptors of a novel series of fused-ring tetrahydropyridine derivatives are described. Some of the compounds showed high affinity for the 5-HT7 receptor. Tetrahydrothienopyridylbutyl-tetrahydrobenzindoles 5d and 5h are potent ligands for the 5-HT7 receptor, with high selectivity over the 5-HT2 receptor and other receptors. These compounds should be useful tools for clarifying the biological role of the 5-HT7 receptor. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00485-7

文献信息

• How to increase the reactivity of [18F]fluoroethyl bromide: [18F]fluoroethylation of amine, phenol and amide functional groups with [18F]FEtBr, [18F]FEtBr/NaI and [18F]FEtOTf
  作者：Ming-Rong Zhang、Kenji Furutsuka、Yuichiro Yoshida、Kazutoshi Suzuki

  DOI：10.1002/jlcr.703

  日期：2003.5

  [18F]Fluoroethyl bromide ([18F]FEtBr) is a useful synthetic precursor to synthesize 18F-labeled compounds. However, the lower reactivity of [18F]FEtBr with amine, phenol and amide functional groups than that of [11C]CH3I partly limits its wide application in the synthesis of [18F]fluoroethylated compounds. The aim of this study was to increase the reactivity of [18F]FEtBr with various nucleophilic substrates for PET tracers containing amine, phenol and amide moieties. The present strategies included (1) adding NaI into the reaction mixture of [18F]FEtBr and substrate, where [18F]FEtI is reversibly formed and becomes more reactive; (2) converting [18F]FEtBr into much more reactive [18F]FEtOTf, similar to conversion of [11C]CH3I into [11C]CH3OTf. By these efforts, the [18F]fluoroethylation efficiency of various substrates containing amine, phenol and amide groups with [18F]FEtBr/NaI and [18F]FEtOTf was significantly improved, compared with the corresponding reaction efficiency with [18F]FEtBr. Copyright © 2003 John Wiley & Sons, Ltd.

  [18F]氟乙基溴 ([18F]FEtBr) 是合成 18F 标记化合物的有用合成前体。然而，[18F]FEtBr与胺、酚和酰胺官能团的反应活性低于[11C]CH3I，部分限制了其在[18F]氟乙基化化合物合成中的广泛应用。本研究的目的是提高 [18F]FEtBr 与各种亲核底物的反应性，用于含有胺、苯酚和酰胺部分的 PET 示踪剂。目前的策略包括（1）将NaI添加到[18F]FEtBr和底物的反应混合物中，其中[18F]FEtI可逆地形成并变得更具反应性； (2) 将[ 18F]FEtBr 转化为更具反应性的[ 18F]FEtOTf ，类似于将[ 11C]CH3I 转化为[ 11C]CH3OTf 。通过这些努力，与[18F]FEtBr的相应反应效率相比，[18F]FEtBr/NaI和[18F]FEtOTf对各种含有胺、酚和酰胺基团的底物的[18F]氟乙基化效率显着提高。版权所有 © 2003 约翰·威利父子有限公司
• Tetrahydrobenzindole derivatives
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：US06498251B1

  公开（公告）日：2002-12-24

  Compounds containing tetrahydrobenzindole which bind to serotonin receptor and are useful in treatment or prevention of disease induced by abnormality of central peripheral serotonin controlling functions.

  含有四氢苯并吲哚的化合物，可结合到血清素受体，并在治疗或预防中枢外周血清素控制功能异常引起的疾病方面发挥作用。
• TETRAHYDROBENZINDOLE DERIVATIVES
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：EP1057814A1

  公开（公告）日：2000-12-06

  This invention creates compounds represented by the following formula (1) which, alone or as a plurality of them simultaneously, act upon serotonin receptors, and thereby provides pharmaceutical compositions that contain these compounds and are useful for the treatment or prevention of diseases which are considered to be induced by the abnormality of central and peripheral serotonin controlling functions. In the formula, R1 is a hydrogen atom, a lower alkyl group or an aralkyl group; R2 is a hydrogen atom or a specified substituent; n is an integer of 2 to 6; and α is the following formula (a), (b), (c), (d) or (e). In formulae (a) and (b), R3 is a hydrogen atom or a specified substituent; X is NR10, NCONR11R12, S, SO, SO2 or O; R10 is a hydrogen atom or a specified substituent; R11 and R12 is independently a hydrogen atom or a lower alkyl; Y is a methylene group or a carbonyl group. In formula (c), R4 is a hydrogen atom or a specified substituent; R5 is a hydrogen atom or a specified substituent; k is 0 or an integer of 1 to 3; m is 0 or an integer of 1 to 3; each of A and B is a group which forms a specified ring via a double bond; k + m is an integer of 1 to 3. In formulae (d) and (e), R4 is as defined above; G is CH2, S, O or C=O; D is CH or N; p is an integer of 1 to 3; each of E and J is a group which forms a benzene ring or a pyridine ring via a double bond; R6 and R7 is independently a hydrogen atom or a lower alkyl or the like specified substituent.

  本发明创造了由下式(1)表示的化合物，这些化合物单独或多个同时作用于血清素受体，从而提供了含有这些化合物的药物组合物，这些组合物可用于治疗或预防被认为是由中枢和外周血清素控制功能异常诱发的疾病。 式中，R1 是氢原子、低级烷基或芳烷基；R2 是氢原子或特定取代基；n 是 2 至 6 的整数；α 是下式 (a)、(b)、(c)、(d) 或 (e)。 在式(a)和(b)中，R3 是氢原子或特定取代基；X 是 NR10、NCONR11R12、S、SO、SO2 或 O；R10 是氢原子或特定取代基；R11 和 R12 独立地是氢原子或低级烷基；Y 是亚甲基或羰基。在式(c)中，R4 是氢原子或特定取代基；R5 是氢原子或特定取代基；k 是 0 或 1 至 3 的整数；m 是 0 或 1 至 3 的整数；A 和 B 各自是通过双键形成特定环的基团；k + m 是 1 至 3 的整数。在式(d)和(e)中，R4 如上定义；G 是 CH2、S、O 或 C＝O；D 是 CH 或 N；p 是 1 至 3 的整数；E 和 J 各自是通过双键形成苯环或吡啶环的基团；R6 和 R7 独立地是氢原子或低级烷基或类似的指定取代基。
• US6498251B1
  申请人：——

  公开号：US6498251B1

  公开（公告）日：2002-12-24
• Tetrahydrothienopyridylbutyl-tetrahydrobenzindoles: New Selective Ligands of the 5-HT7 Receptor
  作者：Chika Kikuchi、Toyokazu Hiranuma、Masao Koyama

  DOI：10.1016/s0960-894x(02)00485-7

  日期：2002.9

  The synthesis and the affinity for the 5-HT7 receptor and other receptors of a novel series of fused-ring tetrahydropyridine derivatives are described. Some of the compounds showed high affinity for the 5-HT7 receptor. Tetrahydrothienopyridylbutyl-tetrahydrobenzindoles 5d and 5h are potent ligands for the 5-HT7 receptor, with high selectivity over the 5-HT2 receptor and other receptors. These compounds should be useful tools for clarifying the biological role of the 5-HT7 receptor. (C) 2002 Elsevier Science Ltd. All rights reserved.