3-((6-fluorohexyl)oxy)-4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazole | 934681-96-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-((6-fluorohexyl)oxy)-4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazole
• 英文别名: 3-(6-fluorohexoxy)-4-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-1,2,5-thiadiazole
• CAS: 934681-96-6
• 化学式: C₁₄H₂₂FN₃OS
• 分子量: 299.413
• InChiKey: JOALYIXMNZZAIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  66.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  L-酒石酸 、 3-((6-fluorohexyl)oxy)-4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazole 以 甲醇 为溶剂， 反应 12.0h， 以60 mg的产率得到
  参考文献：
  名称：

  [EN] XANOMELINE DERIVATIVES AND METHODS FOR TREATING NEUROLOGICAL DISORDERS
  [FR] DÉRIVÉS DE XANOMÉLINE ET MÉTHODES DE TRAITEMENT DE TROUBLES NEUROLOGIQUES

  摘要：

  本文提供的是含有式(I)化合物和/或其盐的化合物；其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12和R13中至少有一个为氟，其余独立地选择氢和氟；而R14、R15、R16、R17、R18、R19、R20、R21、R22和R23独立地选择氢和氘；但是当R1、R2和R3为氟时，那么R4、R5、R6、R7、R8、R9、R10、R11、R12和R13中至少有一个为氟或R14、R15、R16、R17、R18、R19、R20、R21、R22和R23中至少有一个为氘。此外，本文还提供了包含这些化合物的药物和使用这些化合物和药物治疗中枢神经系统疾病的方法。

  公开号：

  WO2021097427A1
• 作为产物：
  描述：

  6-(苄氧基)-1-己醇 在 4-二甲氨基吡啶 、 5% Pd(II)/C(eggshell) 、 四丁基氟化铵 、 氢气 、 palladium(II) hydroxide 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 mineral oil 为溶剂， 反应 2.5h， 生成 3-((6-fluorohexyl)oxy)-4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazole
  参考文献：
  名称：

  Towards the development of new subtype-specific muscarinic receptor radiopharmaceuticals — Radiosynthesis and ex vivo biodistribution of [¹⁸F]3-(4-(2-(2-(2-fluoroethoxy)ethoxy)ethylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5,6-tetrahydropyridine

  摘要：

  毒蕈碱受体与阿尔茨海默病、帕金森病和精神分裂症等神经系统疾病有关。我们合成了噻二唑基四氢吡啶（TZTP）的 19 种衍生物，并通过体外结合试验对其进行了评估。标题化合物是 TZTP 的氟聚乙二醇类似物（4c），随后用氟-18 标记。通过自动合成，在 40 分钟内（n = 3）制备出了氟-18 标记的 4c，平均放射化学收率为 36%（未校正衰变），放射化学纯度高（99%），比活度高（326 GBq/µmol；轰击末）。在有意识的大鼠尾静脉注射[18F]4c后进行的体内外生物分布研究显示，[18F]4c有足够的脑摄取量（注射后5分钟，所有脑区的注射剂量/克湿组织为0.4%-0.7%）；不过，脑内存在大量极性代谢物，因此今后无法将[18F]4c用于中枢神经系统成像。

  DOI：

  10.1139/v10-149

文献信息

• Xanomeline derivatives and methods for treating neurological disorders
  申请人：Karuna Therapeutics, Inc.

  公开号：US11534434B2

  公开（公告）日：2022-12-27

  Provided herein are compounds comprising compounds of formula I and/or salts thereof; wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 is fluorine, and the remainder are independently chosen from hydrogen and fluorine; and R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , and R 23 are independently chosen from hydrogen and deuterium; with the proviso that when R 1 , R 2 , and R 3 are fluorine, then at least one of R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 is fluorine or at least one of R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , and R 23 is deuterium. Also provided are medicaments comprising these compounds and methods for treating central nervous system disorders with the compounds and medicaments described herein.

  本文提供的化合物包括式 I 化合物 和/或其盐； 其中 R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 和 R 13 是氟，其余独立地选自氢和氟；以及 R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 和 R 23 独立地选自氢和氘；但当 R 1 , R 2 和 R 3 为氟，则 R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 和 R 13 是氟或 R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 和 R 23 为氘。此外，还提供了包含这些化合物的药物，以及用本文所述化合物和药物治疗中枢神经系统疾病的方法。
• XANOMELINE DERIVATIVES AND METHODS FOR TREATING NEUROLOGICAL DISORDERS
  申请人：Karuna Therapeutics, Inc.

  公开号：US20210145810A1

  公开（公告）日：2021-05-20

  Provided herein are compounds comprising compounds of formula I and/or salts thereof; wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 is fluorine, and the remainder are independently chosen from hydrogen and fluorine; and R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , and R 23 are independently chosen from hydrogen and deuterium; with the proviso that when R 1 , R 2 , and R 3 are fluorine, then at least one of R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 is fluorine or at least one of R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , and R 23 is deuterium. Also provided are medicaments comprising these compounds and methods for treating central nervous system disorders with the compounds and medicaments described herein.
• Towards the development of new subtype-specific muscarinic receptor radiopharmaceuticals — Radiosynthesis and ex vivo biodistribution of [¹⁸F]3-(4-(2-(2-(2-fluoroethoxy)ethoxy)ethylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5,6-tetrahydropyridine
  作者：Erik M. van Oosten、Alan A. Wilson、David C. Mamo、Bruce G. Pollock、Benoit H. Mulsant、Sylvain Houle、Neil Vasdev

  DOI：10.1139/v10-149

  日期：2010.12

  Muscarinic receptors have been implicated in neurological disorders including Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Nineteen derivatives of thiadiazolyltetrahydropyridine (TZTP), a core that has previously shown high affinities towards muscarinic receptor subtypes, were synthesized and evaluated via in vitro binding assays. The title compound, a fluoro-polyethyleneglycol analog of TZTP (4c), was subsequently labelled with fluorine-18. Fluorine-18-labelled 4c was produced, via an automated synthesis, in an average radiochemical yield of 36% (uncorrected for decay), with high radiochemical purity (>99%) and high specific activity (326 GBq/µmol; end-of-bombardment), within 40 min (n = 3). Ex vivo biodistribution studies following tail-vein injection of [¹⁸F]4c in conscious rats displayed sufficient brain uptake (0.4%–0.7% injected dose / gram of wet tissue in all brain regions at 5 min post injection); however, there were substantial polar metabolites present in the brain, thereby precluding future use of [¹⁸F]4c for imaging in the central nervous system.

  毒蕈碱受体与阿尔茨海默病、帕金森病和精神分裂症等神经系统疾病有关。我们合成了噻二唑基四氢吡啶（TZTP）的 19 种衍生物，并通过体外结合试验对其进行了评估。标题化合物是 TZTP 的氟聚乙二醇类似物（4c），随后用氟-18 标记。通过自动合成，在 40 分钟内（n = 3）制备出了氟-18 标记的 4c，平均放射化学收率为 36%（未校正衰变），放射化学纯度高（99%），比活度高（326 GBq/µmol；轰击末）。在有意识的大鼠尾静脉注射[18F]4c后进行的体内外生物分布研究显示，[18F]4c有足够的脑摄取量（注射后5分钟，所有脑区的注射剂量/克湿组织为0.4%-0.7%）；不过，脑内存在大量极性代谢物，因此今后无法将[18F]4c用于中枢神经系统成像。
• [EN] XANOMELINE DERIVATIVES AND METHODS FOR TREATING NEUROLOGICAL DISORDERS<br/>[FR] DÉRIVÉS DE XANOMÉLINE ET MÉTHODES DE TRAITEMENT DE TROUBLES NEUROLOGIQUES
  申请人：KARUNA THERAPEUTICS INC

  公开号：WO2021097427A1

  公开（公告）日：2021-05-20

  Provided herein are compounds comprising compounds of formula (I) and/or salts thereof; wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is fluorine, and the remainder are independently chosen from hydrogen and fluorine; and R14, R15, R16, R17, R18, R19, R20, R21, R22, and R23 are independently chosen from hydrogen and deuterium; with the proviso that when R1, R2, and R3 are fluorine, then at least one of R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is fluorine or at least one of R14, R15, R16, R17, R18, R19, R20, R21, R22 , and R23 is deuterium. Also provided are medicaments comprising these compounds and methods for treating central nervous system disorders with the compounds and medicaments described herein.

  本文提供的是含有式(I)化合物和/或其盐的化合物；其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12和R13中至少有一个为氟，其余独立地选择氢和氟；而R14、R15、R16、R17、R18、R19、R20、R21、R22和R23独立地选择氢和氘；但是当R1、R2和R3为氟时，那么R4、R5、R6、R7、R8、R9、R10、R11、R12和R13中至少有一个为氟或R14、R15、R16、R17、R18、R19、R20、R21、R22和R23中至少有一个为氘。此外，本文还提供了包含这些化合物的药物和使用这些化合物和药物治疗中枢神经系统疾病的方法。