(4-(aminomethyl)-1-benzylpiperidin-4-yl)methanamine | 52419-85-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (4-(aminomethyl)-1-benzylpiperidin-4-yl)methanamine
• 英文别名: 4,4-bis-aminomethyl-1-benzyl-piperidine；C-(4-aminomethyl-1-benzyl-piperidin-4-yl)-methylamine；4,4-di(aminomethyl)-1-(phenylmethyl) piperidine；4,4-Bis-aminomethyl-1-benzyl-piperidin；[4-(aminomethyl)-1-benzylpiperidin-4-yl]methanamine
• CAS: 52419-85-9
• 化学式: C₁₄H₂₃N₃
• 分子量: 233.357
• InChiKey: ANBVVWACKQVQBD-UHFFFAOYSA-N

物化性质

• 沸点：
  137 °C(Press: 0.4 Torr)
• 密度：
  1.042±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  55.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-(aminomethyl)-1-benzylpiperidin-4-yl)methanamine 在 吡啶 、 sodium hypochlorite 、 双氧水 作用下， 以 甲醇 、 水 为溶剂， 生成 N-[(8-benzyl-2,3,8-triaza-spiro[4.5]dec-3-en-2-yl)-methylsulfanyl-methylidene]-3-chlorobenzenesulfonamide
  参考文献：
  名称：

  N′-(Arylsulfonyl)pyrazoline-1-carboxamidines as Novel, Neutral 5-Hydroxytryptamine 6 Receptor (5-HT₆R) Antagonists with Unique Structural Features

  摘要：

  The 5-HT6 receptor (5-HT6R) has been in the spotlight for several years regarding CNS-related diseases. We set out to discover novel, neutral 5-HT6R antagonists to improve off-target selectivity compared to basic amine-containing scaffolds dominating the field. High-throughput screening identified the N'-(sulfonyl)pyrazoline-1-carboxamidine scaffold as a promising neutral core for starting hit-to-lead. Medicinal chemistry, molecular modeling, small molecule NMR and X-ray crystallography were subsequently applied to optimize the leads into antagonists (compounds 1-49) displaying high 5-HT6R affinity with optimal off-target selectivity. Unique structural features include a pseudoaromatic system and an internal hydrogen bond freezing the bioactive conformation. While physicochemical properties and CNS availability were generally favorable, significant efforts had to be made to improve metabolic stability. The optimized structure 42 is an extremely selective, hERG-free, high-affinity 5-HT6R antagonist showing good human in vitro metabolic stability. Rat pharrnacokinetic data were sufficiently good to enable further in vivo profiling.

  DOI：

  10.1021/jm200466r
• 作为产物：
  描述：

  N,N-双(2-氯乙基)苯甲胺 在 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 环戊基甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (4-(aminomethyl)-1-benzylpiperidin-4-yl)methanamine
  参考文献：
  名称：

  N′-(Arylsulfonyl)pyrazoline-1-carboxamidines as Novel, Neutral 5-Hydroxytryptamine 6 Receptor (5-HT₆R) Antagonists with Unique Structural Features

  摘要：

  The 5-HT6 receptor (5-HT6R) has been in the spotlight for several years regarding CNS-related diseases. We set out to discover novel, neutral 5-HT6R antagonists to improve off-target selectivity compared to basic amine-containing scaffolds dominating the field. High-throughput screening identified the N'-(sulfonyl)pyrazoline-1-carboxamidine scaffold as a promising neutral core for starting hit-to-lead. Medicinal chemistry, molecular modeling, small molecule NMR and X-ray crystallography were subsequently applied to optimize the leads into antagonists (compounds 1-49) displaying high 5-HT6R affinity with optimal off-target selectivity. Unique structural features include a pseudoaromatic system and an internal hydrogen bond freezing the bioactive conformation. While physicochemical properties and CNS availability were generally favorable, significant efforts had to be made to improve metabolic stability. The optimized structure 42 is an extremely selective, hERG-free, high-affinity 5-HT6R antagonist showing good human in vitro metabolic stability. Rat pharrnacokinetic data were sufficiently good to enable further in vivo profiling.

  DOI：

  10.1021/jm200466r

文献信息

• Tricyclic Spiro Compound Comprising Acyl Group Bound to Nitrogen Atom in the Ring
  申请人：Nishida Hidemitsu

  公开号：US20090076015A1

  公开（公告）日：2009-03-19

  It is intended to provide an anticoagulant that has an extremely excellent FXa inhibitory action and an extremely weak hERG channel inhibitory action and can be orally administered, which is a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof.

  该文旨在提供一种极为优异的FXa抑制剂，具有极弱的hERG通道抑制作用，并可口服，该化合物由以下公式(I)所代表，或其药学上可接受的盐。
• SULFONYLPYRAZOLE AND SULFONYLPYRAZOLINE CARBOXAMIDINE DERIVATIVES AS 5-HT6 ANTAGONISTS
  申请人：Van Loevezijn Arnold

  公开号：US20080311179A1

  公开（公告）日：2008-12-18

  This invention concerns compounds of the general formula (1). and derivatives thereof, which are antagonists of 5-HT 6 receptors, wherein the symbols have the meanings given in the description. The invention also concerns methods for the preparation of these compounds, to novel intermediates useful for their synthesis, and to uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in treating at least on disease or condition chosen from Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes.

  本发明涉及通式（1）的化合物及其衍生物，它们是5-HT6受体拮抗剂，其中符号的含义如说明书所示。本发明还涉及制备这些化合物的方法，对于其合成有用的新型中间体，以及这些化合物和组合物的用途，特别是将它们用于向患者施用以达到治疗帕金森病、亨廷顿舞蹈症、精神分裂症、焦虑、抑郁症、躁郁症、精神病、癫痫、强迫症、情绪障碍、偏头痛、阿尔茨海默病、与年龄相关的认知衰退、轻度认知障碍、睡眠障碍、进食障碍、厌食症、贪食症、暴食症、惊恐发作、不安定症、注意力缺陷多动障碍、注意力缺陷障碍、戒断可卡因、乙醇、尼古丁或苯二氮平的滥用、疼痛、与脊髓损伤或头部损伤有关的疾病、脑积水、功能性肠道障碍、肠易激综合征、肥胖症和2型糖尿病等至少一种疾病或症状的治疗效果。
• Sulfonylpyrazole and sulfonylpyrazoline carboxamidine derivatives as 5-HT6 antagonists
  申请人：Solvay Pharmaceuticals B.V.

  公开号：US07728018B2

  公开（公告）日：2010-06-01

  This invention concerns compounds of the general formula (1): and derivatives thereof, which are antagonists of 5-HT6 receptors, wherein the symbols have the meanings given in the description. The invention also concerns methods for the preparation of these compounds, to novel intermediates useful for their synthesis, and to uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in treating at least on disease or condition chosen from Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes.

  这项发明涉及一般式（1）的化合物及其衍生物，它们是5-HT6受体的拮抗剂，其中符号具有描述中所给出的含义。该发明还涉及制备这些化合物的方法，对于其合成有用的新中间体，以及这些化合物和组合物的用途，特别是将它们用于给患者治疗至少一种疾病或病状，包括帕金森病、亨廷顿舞蹈症、精神分裂症、焦虑症、抑郁症、躁郁症、精神病、癫痫、强迫症、情绪障碍、偏头痛、阿尔茨海默病、与年龄相关的认知衰退、轻度认知障碍、睡眠障碍、进食障碍、厌食症、贪食症、暴食症、惊恐发作、不安躁动、注意力缺陷多动障碍、注意力缺陷障碍、戒断可卡因、乙醇、尼古丁或苯二氮平的滥用、疼痛、与脊髓损伤或头部损伤相关的疾病、脑积水、功能性肠道紊乱、肠易激综合征、肥胖症和2型糖尿病。
• TRICYCLIC SPIRO COMPOUND COMPRISING ACYL GROUP BOUND TO NITROGEN ATOM IN THE RING
  申请人：MOCHIDA PHARMACEUTICAL CO., LTD.

  公开号：EP1864984A1

  公开（公告）日：2007-12-12

  It is intended to provide an anticoagulant that has an extremely excellent FXa inhibitory action and an extremely weak hERG channel inhibitory action and can be orally administered, which is a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof.

  本研究旨在提供一种具有极佳的 FXa 抑制作用和极弱的 hERG 通道抑制作用且可口服的抗凝血剂，它是由下式（I）代表的化合物或其药学上可接受的盐。
• WO2008/34863
  申请人：——

  公开号：——

  公开（公告）日：——