(4-fluorophenyl)(1-methylpiperidin-4-yl)methanone | 144734-22-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-fluorophenyl)(1-methylpiperidin-4-yl)methanone
• 英文别名: 1-methyl-4-(4-fluorobenzoyl)piperidine；4-Fluorophenyl 1-methylpiperidin-4-yl methanone；(4-fluorophenyl)-(1-methylpiperidin-4-yl)methanone
• CAS: 144734-22-5
• 化学式: C₁₃H₁₆FNO
• 分子量: 221.275
• InChiKey: ISGZTZNRWOQFNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-fluorophenyl)(1-methylpiperidin-4-yl)methanone 在 sodium tetrahydroborate 、 硫酸 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 反应 40.0h， 生成 (±)-methyl 4-((2-(4-fluorophenyl)-1'-methylspiro[indoline-3,4'-piperidin]-1-yl)methyl)benzoate
  参考文献：
  名称：

  Harnessing the Role of HDAC6 in Idiopathic Pulmonary Fibrosis: Design, Synthesis, Structural Analysis, and Biological Evaluation of Potent Inhibitors

  摘要：

  DOI：

  10.1021/acs.jmedchem.1c00184
• 作为产物：
  描述：

  4-[(4-fluorophenyl)methyl]-1-methylpiperidine 在 三氟乙酸 、 吡啶 、 2-吡啶甲酸 、 叔丁基过氧化氢 、 iron(III) chloride hexahydrate 作用下， 以 水 、 乙腈 为溶剂， 反应 48.08h， 以37%的产率得到(4-fluorophenyl)(1-methylpiperidin-4-yl)methanone
  参考文献：
  名称：

  偏远苯甲酰CH位置处铁催化脂肪胺的氧化官能化

  摘要：

  我们报告了一种铁催化方法的发展，该方法用于在脂肪族胺底物中的苄基C（sp 3）-H键进行选择性的氧官能化。对于远离胺官能团（至少三个碳原子）的苄基CH键，该转化过程具有选择性。通过用三氟乙酸对胺进行原位质子化，可实现较高的位点选择性，从而使更传统的反应性C–H位（即α至氮原子）失活。通过多种含胺的生物活性分子的合成和衍生化，证明了该方法的范围和合成实用性。

  DOI：

  10.1021/acs.orglett.6b02003

文献信息

• Urea derivatives as calcium channel blockers
  申请人：Pajouhesh Hassan

  公开号：US20060063775A1

  公开（公告）日：2006-03-23

  Urea derivatives which comprise piperidine or piperazine rings and further substitution are effective in ameliorating conditions characterized by unwanted calcium ion channel activity.

  含有哌啶或哌嗪环及其进一步取代的尿素衍生物，在改善由不良钙离子通道活性所表征的状况方面效果显著。
• Ketanserin analogs: structure-affinity relationships for 5-HT2 and 5-HT1C serotonin receptor binding
  作者：Jeff L. Herndon、Abd Ismaiel、Stacy P. Ingher、M. Teitler、Richard A. Glennon

  DOI：10.1021/jm00104a017

  日期：1992.12

  prototypic 5-HT2 serotonin antagonist; although it has been an important tool for the study of serotonin pharmacology, it has had relatively little impact on drug design because remarkably little is known about its structure-affinity relationships. Furthermore, ketanserin also binds at 5-HT1C receptors and even less is known about the influence of its structural features on 5-HT1C receptor affinity. The present

  酮色林是原型5-HT2血清素拮抗剂。尽管它一直是研究5-羟色胺药理学的重要工具，但它对药物设计的影响相对较小，因为对其结构亲和性关系知之甚少。此外，酮色林还与5-HT1C受体结合，对其结构特征对5-HT1C受体亲和力的影响知之甚少。本研究表明，酮色林的4-氟苯甲酰基部分的氟和羰基对5​​-HT2结合的贡献很小，完整的苯甲酰基哌啶部分是重要的特征。哌啶环的开环降低了亲和力。尽管喹唑啉-2,4-二酮部分也有助于结合，它似乎起着较小的作用，并且可以通过保留5-HT2亲和力在结构上简化。例如，N-（4-苯基丁基）-4-（4-氟苯甲酰基）哌啶（39）以与酮色林（Ki = 3.5 nM）几乎相同的亲和力（Ki = 5.3 nM）结合。所有检测到的化合物在5-HT1C位点的结合亲和力均比酮色林低，某些简化的类似物以5-HT2C结合酮色林的5-HT1C选择性结合近十倍。但是，没有显示> 120倍的选择性。
• UREA DERIVATIVES AS CALCIUM CHANNEL BLOCKERS
  申请人：Pajouhesh Hassan

  公开号：US20080207633A1

  公开（公告）日：2008-08-28

  Urea derivatives which comprise piperidine or piperazine rings and further substitution are effective in ameliorating conditions characterized by unwanted calcium ion channel activity.

  含有哌啶或哌嗪环且进一步置换的尿素衍生物对于改善由于不必要的钙离子通道活性所表现出的情况是有效的。
• Novel Heterocyclic Substituted Carbonyl Derivatives and Their Use as Dopamine D3 Receptor Ligands
  申请人：Hendrix James A.

  公开号：US20090247509A1

  公开（公告）日：2009-10-01

  The invention relates to heterocyclic substituted carbonyl derivatives that display selective binding to dopamine D 3 receptors. In another aspect, the invention relates to a method for treating central nervous system disorders associated with the dopamine D 3 receptor activity in a patient in need of such treatment comprising administering to the subject a therapeutically effective amount of said compounds for alleviation of such disorder. The central nervous system disorders that may be treated with these compounds include Psychotic Disorders, Substance Dependence, Substance Abuse, Dyskinetic Disorders (e.g. Parkinson's Disease, Parkinsonism, Neuroleptic-Induced Tardive Dyskinesia, Gilles de la Tourette Syndrome and Huntington's Disease), Dementia, Anxiety Disorders, Sleep Disorders, Circadian Rhythm Disorders and Mood Disorders. The subject invention is also directed towards processes for the preparation of the compounds described herein as well as methods for making and using the compounds as imaging agents for dopamine D 3 receptors.

  本发明涉及杂环取代羰基衍生物，其表现出对多巴胺D3受体的选择性结合。另一方面，本发明涉及一种治疗与多巴胺D3受体活性相关的中枢神经系统疾病的方法，该方法包括向需要此类治疗的患者施用所述化合物的治疗有效量，以缓解此类疾病。这些化合物可以治疗的中枢神经系统疾病包括精神疾病、物质依赖、物质滥用、运动障碍（例如帕金森病、帕金森综合症、神经阻滞引起的迟发性运动障碍、吉尔斯-德-拉-图雷综合症和亨廷顿病）、痴呆、焦虑症、睡眠障碍、昼夜节律紊乱和情绪障碍。本发明还涉及制备所述化合物的方法以及将所述化合物作为多巴胺D3受体成像剂的制备和使用方法。
• Novel heterocyclic substituted carbonyl derivatives and their use as dopamine D3 receptor ligands
  申请人：Hendrix A. James

  公开号：US20070161641A1

  公开（公告）日：2007-07-12

  The invention relates to heterocyclic substituted carbonyl derivatives that display selective binding to dopamine D 3 receptors. In another aspect, the invention relates is to a method for treating central nervous system disorders associated with the dopamine D 3 receptor activity in a patient in need of such treatment comprising administering to the subject a therapeutically effective amount of said compounds for alleviation of such disorder. The central nervous system disorders that may be treated with these compounds include Psychotic Disorders, Substance Dependence, Substance Abuse, Dyskinetic Disorders (e.g. Parkinson's Disease, Parkinsonism, Neuroleptic-Induced Tardive Dyskinesia, Gilles de la Tourette Syndrome and Huntington's Disease), Dementia, Anxiety Disorders, Sleep Disorders, Circadian Rhythm Disorders and Mood Disorders. The subject invention is also directed towards processes for the preparation of the compounds described herein as well as methods for making and using the compounds as imaging agents for dopamine D 3 receptors.

  本发明涉及杂环取代羰基衍生物，其具有选择性地与多巴胺D3受体结合。另一方面，本发明涉及一种治疗中枢神经系统疾病的方法，该疾病与多巴胺D3受体活性有关，包括对患者进行治疗，向患者施用所述化合物的治疗有效量，以缓解此类疾病。这些化合物可以治疗的中枢神经系统疾病包括精神病性障碍、物质依赖、物质滥用、运动障碍（例如帕金森病、帕金森综合症、神经阻滞剂引起的迟发性运动障碍、吉尔·德·拉·图雷特综合症和亨廷顿病）、痴呆、焦虑症、睡眠障碍、昼夜节律紊乱和情绪障碍。本发明还涉及所述化合物的制备过程，以及将所述化合物作为多巴胺D3受体成像剂的制备和使用方法。