tetrahydro-4H-pyran-4,4-dimethaneamine | 119669-84-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: tetrahydro-4H-pyran-4,4-dimethaneamine
• 英文别名: (4-(aminomethyl)tetrahydropyran-4-yl)methanamine；1,3-(2,2-(4-oxacyclohexyl))-propyl diamine；1,3-(2,2-(4-oxacyclohexyl))propyldiamine；tetrahydro-4H-pyran-4,4-dimethanamine；C-(4-aminomethyl-tetrahydro-pyran-4-yl)-methylamine；tetrahydro-4H-pyrane-4,4-dimethanamine；[4-(Aminomethyl)oxan-4-yl]methanamine
• CAS: 119669-84-0
• 化学式: C₇H₁₆N₂O
• mdl: MFCD09056751
• 分子量: 144.217
• InChiKey: HFAYPKGISTWLIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  61.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tetrahydro-4H-pyran-4,4-dimethaneamine 在 sodium hypochlorite 、 双氧水 作用下， 以 甲醇 、 水 为溶剂， 生成 8-氧杂-2,3-二氮杂-螺[4.5]癸-2-烯
  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：

  四氢吡喃-4,4-二甲腈 在 diborane(6) 作用下， 以 四氢呋喃 为溶剂， 以62%的产率得到tetrahydro-4H-pyran-4,4-dimethaneamine
  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

• 一种治疗肿瘤细胞增生性疾病的铂（II）类化 合物
  申请人：北京市丰硕维康技术开发有限责任公司

  公开号：CN104995201B

  公开（公告）日：2017-12-22

  本发明公开了一类离去基团丙二酸衍生物“2”位取代基含有伯氨基、仲氨基、叔氨基、季氨基的丙二酸衍生物的铂类化合物及其药学上可接受的盐、其制备方法及含有以上化合物的药物组合物。本发明还公开了以上化合物在治疗细胞增殖性疾病，特别是治疗癌症中的用途。本发明铂类化合物具有高的水中溶解度，毒副作用低。
• PLATINUM COMPOUND HAVING AMINO OR ALKYLAMINO-CONTAINING SUCCINIC ACID DERIVATIVES AS LEAVING GROUP, PREPARTION METHOD THEREOF, AND USE THEREOF
  申请人：BEIJING FSWELCOME TECHNOLOGY DEVELOPMENT CO., LTD.

  公开号：US20140349985A1

  公开（公告）日：2014-11-27

  Disclosed are a category of platinum compounds having amino- or alkylamino-containing succinato derivatives as leaving group, or pharmaceutically acceptable salts thereof, preparation method thereof, and medicinal compositions containing the compounds. Also disclosed is a use of the compounds in treating cell proliferative diseases, especially cancers. The platinum compounds of the present invention have high water solubility and small toxic side effect.

  本发明揭示了一类铂化合物，其具有氨基或烷基氨基含有琥珀酸酯衍生物作为脱离基团，或其药用可接受的盐，以及其制备方法，以及含有这些化合物的药物组合物。本发明还揭示了这些化合物在治疗细胞增殖性疾病，特别是癌症方面的用途。本发明的铂化合物具有高水溶性和小毒副作用。
• PLATINUM COMPOUNDS FOR TREATING CELL PROLIFERATIVE DISEASES, PREPARATION METHOD AND USE THEREOF
  申请人：Chen Xiaoping

  公开号：US20140142079A1

  公开（公告）日：2014-05-22

  Disclosed are a class of platinum compounds with a leaving group of malonic acid derivatives containing amino and alkylamino, their pharmaceutically acceptable salts, their preparation methods and pharmaceutical composites comprising them. Disclosed also are for the uses of the compounds in the treatment of cell proliferative diseases, particularly for the treatment of cancers. The present platinum compounds have high water solubility and low toxicity.

  本文披露了一类铂化合物，其离去基为含有氨基和烷基氨基的丙二酸衍生物，以及它们的药用可接受盐、制备方法和包括它们的药用组合物。本文还披露了这些化合物在治疗细胞增殖性疾病，特别是治疗癌症方面的用途。这些铂化合物具有高水溶性和低毒性。
• 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。