5-fluoro-3-[(4-piperidinyl)methyl]-1H-indole | 75259-64-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-fluoro-3-[(4-piperidinyl)methyl]-1H-indole
• 英文别名: 5-fluoro-3-<(4-piperidinyl)methyl>-1H-indole；5-fluoro-3-(piperidin-4-ylmethyl)-1H-indole；5-fluoro-3-(4-piperidinylmethyl)indole；4-(5-fluoro-1H-indol-3-ylmethyl)piperidine；4-[(5-fluoro-3-indolyl)methyl]piperidine；5-fluoro-3-(4-piperidinylmethyl)-1H-indole
• CAS: 75259-64-2
• 化学式: C₁₄H₁₇FN₂
• 分子量: 232.301
• InChiKey: FFWFFOAMLOOINZ-UHFFFAOYSA-N

物化性质

• 熔点：
  160 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  404.9±35.0 °C(Predicted)
• 密度：
  1.176±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  27.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-fluoro-3-[(4-piperidinyl)methyl]-1H-indole 在 二异丁基氢化铝 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 甲苯 、 苯 为溶剂， 反应 40.33h， 生成 [11C]-RPR-72840A
  参考文献：
  名称：

  Synthesis of [11C]RPR-72840A and its evaluation as a radioligand for the serotonin reuptake site in positron emission tomography

  摘要：

  RPR-72840A, an inhibitor of serotonin reuptake, was labelled with carbon-11. The synthesis of the nonradioactive precursor, which exhibited some unexpected chemistry, and its reaction with [C-11]phosgene affording [C-11]RPR-72840A are described. Biodistribution studies in rats and PET studies in baboons were conducted to evaluate [C-11]RPR-72840A as a tracer for PET imaging of the serotonin reuptake system. (C) 1997, Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(96)00256-8
• 作为产物：
  描述：

  5-氟吲哚 在 盐酸 、 lithium aluminium tetrahydride 、 甲基碘化镁 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 9.25h， 生成 5-fluoro-3-[(4-piperidinyl)methyl]-1H-indole
  参考文献：
  名称：

  3-（4-哌啶基烷基）吲哚，神经元5-羟色胺摄取的选择性抑制剂。

  摘要：

  合成了一系列的3-（4-哌啶基烷基）吲哚并测试了其作为生物胺的吸收抑制剂。生化数据和行为测试证明，这些化合物中的某些在阻断5-羟色胺（5-HT）吸收方面非常有效且选择性很高。讨论了结构-活性关系。该系列中最有趣的成员是吲哚平3- [2-（4-哌啶基）乙基]吲哚（1），用于临床研究。

  DOI：

  10.1021/jm00186a005

文献信息

• New indole derivatives as potent and selective serotonin uptake inhibitors
  作者：Jean Luc Malleron、Claude Gueremy、Serge Mignani、Jean Francois Peyronel、Alain Truchon、Jean Charles Blanchard、Adam Doble、Pierre Laduron、Odile Piot

  DOI：10.1021/jm00061a010

  日期：1993.4

  series of new indole derivatives (2-28) has been prepared in the search for novel 5-HT uptake inhibitors. These compounds were obtained by the condensation of N-(chloroalkyl) naphthalenesultam derivatives with the appropriate amine in presence of a base, at reflux of DMF or THF. The yields were moderate (12-56%), except for the piperazine derivative 20 (85%). The affinity of the compounds for uptake site

  为了寻找新的5-HT摄取抑制剂，已经制备了一系列新的吲哚衍生物（2-28）。在DMF或THF的回流下，在碱的存在下，通过将N-（氯烷基）萘磺酰胺衍生物与适当的胺缩合获得这些化合物。除了哌嗪衍生物20（85％）以外，产率中等（12-56％）。测量了化合物对摄取位点和5-HT 2，α1和D 2受体的亲和力。通过5-HTP诱导症状的增强作用在体内研究了某些化合物。最有效和选择性最大的化合物（摄取的5-HT2与α1，D2位点相比）含有3-[（（4-哌啶基）甲基]吲哚部分。5-氟-3-[（4-哌啶基）甲基]吲哚本身（化合物1）对摄取位点显示出高亲和力，但缺乏体内活性。该化合物的N-甲基化消除了亲和力。相比之下，通过连接至萘磺胺或相关杂环的双碳链进行的N取代导致化合物对摄取位点表现出高亲和力。其中之一是1- [2- [4-（（5-氟-1H-吲哚-3-基）甲基-1-哌啶基]乙基] -5,6-二氢-1H，4H-1
• Heterocyclic derivatives, their preparation and medicinal products
  申请人：Rhone-Poulenc Sante

  公开号：US05114949A1

  公开（公告）日：1992-05-19

  Compounds are disclosed of formula: R.sub.1 --(CH.sub.2).sub.n --Het in which R.sub.1 represents a residue of formula ##STR1## X represents a hydrogen atom or an alkyl radical, Y represents a hydrogen atom or an alkyl or alkoxy radical, Z represents an alkyl radical, n is equal to 2 or 3, Het represents a substituted piperidino (substituted at the 4-position with a 1-indenylidene, 1-indenyl or 1-indanyl radical or with a chain --(CH.sub.2).sub.m --R.sub.2 or .dbd.CH--R.sub.2), substituted 1,2,3,6-tetrahydro-1-pyridyl (substituted at the 4-position with a chain --(CH.sub.2).sub.m --R.sub.2), m is equal to 1 or 2, and R.sub.2 represents an optionally substituted 2- or 3-indolyl radical, a 1- or 2-indanyl, 1- or 2-indenyl, an optionally substituted 1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-2-yl radical, a 1,2,3,4-tetrahydro-3-quinolyl radical, an optionally substituted 1,2,3,4-tetrahydro-2-naphthyl radical or a 1-indolyl radical, their preparation and medicinal products containing them.

  揭示了具有以下结构的化合物：R.sub.1--(CH.sub.2).sub.n--Het，其中R.sub.1代表以下结构的残基##STR1##X代表氢原子或烷基基团，Y代表氢原子或烷基或烷氧基团，Z代表烷基基团，n等于2或3，Het代表取代的哌啶基（在4位取代有1-茚基亚甲基、1-茚基或1-茚基基团或具有链--(CH.sub.2).sub.m--R.sub.2或.dbd.CH--R.sub.2)，取代的1,2,3,6-四氢-1-吡啶基（在4位取代有链--(CH.sub.2).sub.m--R.sub.2），m等于1或2，R.sub.2代表可选取代的2-或3-吲哚基团，1-或2-茚基、1-或2-茚基、可选取代的1,2,3,4-四氢-5H-吡啶并[4,3-b]吲哚-2-基团、1,2,3,4-四氢-3-喹啉基团、可选取代的1,2,3,4-四氢-2-萘基团或1-吲哚基团，它们的制备以及含有它们的药物产品。
• Antidepressant azaheterocyclylmethyl derivatives of 1,4,5-trioxa-phenanthrene
  申请人：Wyeth

  公开号：US20020193401A1

  公开（公告）日：2002-12-19

  Compounds of the formula 1 useful for the treatment of diseases such as depression (including but not limited to major depressive disorder, childhood depression and dysthymia), anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder attention deficit disorder (with and without hyperactivity), obsessive compulsive disorder (including trichotillomania), social anxiety disorder, generalized anxiety disorder, obesity, eating disorders such as anorexia nervosa, bulimia nervosa, vasomotor flushing, cocaine and alcohol addiction, sexual dysfunction and related illnesses.

  该式的化合物用于治疗疾病，如抑郁症（包括但不限于重度抑郁症、儿童抑郁症和慢性抑郁症）、焦虑症、恐慌障碍、创伤后应激障碍、经前期失调性障碍、注意力缺陷障碍（有或无多动症）、强迫症（包括拔毛症）、社交焦虑障碍、广泛性焦虑障碍、肥胖症、进食障碍，如厌食症、暴食症、血管运动潮红、可卡因和酒精成瘾、性功能障碍及相关疾病。
• Antidepressant azaheterocyclymethyl derivatives of 2,3-dihydro-1,4-dioxino &lsqb;2,3-f&rsqb;quinoline
  申请人：Wyeth

  公开号：US06458802B1

  公开（公告）日：2002-10-01

  Compounds of the formula: are useful for the treatment of depression (including but not limited to major depressive disorder, childhood depression and dysthymia), anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder (also known as pre-menstrual syndrome), attention deficit disorder (with and without hyperactivity), obsessive compulsive disorder, social anxiety disorder, generalized anxiety disorder, obesity, eating disorders such as anorexia nervosa, bulimia nervosa, vasomotor flushing, cocaine and alcohol addiction, sexual dysfunction and related illnesses.

  该公式化合物对抑郁症（包括但不限于重性抑郁障碍、儿童抑郁症和心境低落）、焦虑、恐慌障碍、创伤后应激障碍、经前期失调性障碍（也称为经前综合症）、注意力缺陷障碍（伴有和不伴有多动症）、强迫症、社交焦虑障碍、广泛性焦虑障碍、肥胖症、厌食症、暴食症、潮红、可卡因和酒精成瘾、性功能障碍及相关疾病的治疗具有用处。
• Synthesis and antidepressant-like activity of novel alkoxy-piperidine derivatives targeting SSRI/5-HT1A/5-HT7
  作者：Wen-Tao Wang、Hao Qian、Jian-Wei Wu、Xiao-Wen Chen、Jian-Qi Li

  DOI：10.1016/j.bmcl.2019.126769

  日期：2019.12

  alkoxy-piperidine derivatives were synthesized and evaluated for their serotonin reuptake inhibitory and binding affinities for 5-HT1A/5-HT7 receptors. In vivo antidepressant activities of the selective compounds were explored using the forced swimming test (FST) and tail suspension test (TST) in mice. The results showed that compounds 7a (reuptake inhibition (RUI), IC50 = 177 nM; 5-HT1A, Ki = 12 nM; 5-HT7, Ki =

  合成了一系列新颖的烷氧基-哌啶衍生物，并评估了它们对5-HT 1A / 5-HT 7受体的5-羟色胺再摄取抑制和结合亲和力。使用强制游泳试验（FST）和尾部悬浮试验（TST）在小鼠中探索了选择性化合物的体内抗抑郁活性。结果显示化合物7a（再摄取抑制（RUI），IC 50 = 177 nM; 5-HT 1A，K i = 12 nM; 5-HT 7，K i = 25 nM ）和15g（RUI，IC 50 = 85） nM; 5-HT 1A，K i= 17 nM；5-HT 7（K i = 35 nM）是动物行为模型中潜在的抗抑郁药，具有高5-HT 1A / 5-HT 7受体亲和力和适度的5-羟色胺再摄取抑制作用，并且在体外具有良好的代谢稳定性。