(6-methoxy-1-methyl-1-trifluoromethyl-isochroman-7-ylmethyl)-(2-phenyl-piperidin-3-yl)-amine

• 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: (6-methoxy-1-methyl-1-trifluoromethyl-isochroman-7-ylmethyl)-(2-phenyl-piperidin-3-yl)-amine
• 英文别名: N-[[6-methoxy-1-methyl-1-(trifluoromethyl)-3,4-dihydroisochromen-7-yl]methyl]-2-phenylpiperidin-3-amine
• 化学式: C₂₄H₂₉F₃N₂O₂
• 分子量: 434.502
• InChiKey: ODEBBNRINYMIRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3-[(1R)-6-methoxy-1-methyl-1-trifluoromethylisochroman-7-yl]methylamino-2-phenylpiperidine 、 6-methoxy-1-methyl-1-trifluoromethyl-isochroman-7-carbaldehyde 、 (2s-3s)-2-Phenyl-piperidin-3-ylamine dimandelate 、 、 (6-methoxy-1-methyl-1-trifluoromethyl-isochroman-7-ylmethyl)-(2-phenyl-piperidin-3-yl)-amine 在 水 、 sodium hydroxide 、 layer 、 二氯甲烷 、 Brine 、 Sodium sulfate-III 、 crude product 作用下， 以 二氯甲烷 、 乙醇 为溶剂， 反应 19.75h， 以to yield 4.66 g (32% ) of (6-methoxy-1-methyl-1-trifluoromethyl-isochroman-7-ylmethyl)-(2-phenyl-piperidin-3-yl)-amine (S)-(+)-mandelate的产率得到(6-methoxy-1-methyl-1-trifluoromethyl-isochroman-7-ylmethyl)-(2-phenyl-piperidin-3-yl)-amine (S)-(+)-mandelate
  参考文献：
  名称：

  Process for the preparation of piperidinylaminomethyl trifluoromethyl cyclic ether compounds

  摘要：

  本发明涉及一种制备式Ia和Ib的哌啶基氨甲基三氟甲基环醚化合物的对映异构体混合物的新工艺及其药学上可接受的盐，其中R1是C1-C6烷基；R2是C1-C6烷基，卤代C1-C6烷基或苯基或取代苯基；R3是氢或卤素；m为零、一或二，所述混合物在式Ia的化合物中高度富集，并且本发明涉及一种用于制备式Ia和Ib化合物的中间体化合物的新工艺和纯化工艺。

  公开号：

  US20030236268A1

文献信息

• Pharmaceutical composition and method of modulating cholinergic function in a mammal
  申请人：Pfizer Inc.

  公开号：US20030008892A1

  公开（公告）日：2003-01-09

  A pharmaceutical composition and method of modulating cholinergic function in a mammal comprising administration of a NRPA compound or a pharmaceutically acceptable salt thereof; and an anti-emetic/anti-nausea agent or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier. The NRPA compound and the anti-emetic/anti-nausea agent are present in amounts that render the composition effective modulating cholinergic function or in the treatment of a diorder or condition selected from inflammatory bowel disease (including but not limited to ulcerative colitis, pyoderma gangrenosum and Crohn's disease), irritable bowel syndrome, spastic dystonia, chronic pain, acute pain, celiac sprue, pouchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis (ALS), cognitive dysfunction, hypertension, bulimia, anorexia, obesity, cardiac arrythmias, gastric acid hypersecretion, ulcers, pheochromocytoma, progressive supranuclear palsy, chemical dependencies and addictions (e.g., dependencies on, or addictions to nicotine (and/or tobacco products), alcohol, benzodiazepines, barbiturates, opioids or cocaine), headache, migraine, stroke, traumatic brain injury (TBI), obsessive-compulsive disorder (OCD), psychosis, Huntington's chorea, tardive dyskinesia, hyperkinesia, dyslexia, schizophrenia, multi-infarct dementia, age-related cognitive decline, epilepsy, including petit mal absence epilepsy, senile dementia of the Alzheimer's type (AD), Parkinson's disease (PD), attention deficit hyperactivity disorder (ADHD) and Tourette's Syndrome. The method of using these compositions is also disclosed.

  一种药物组合物及其在哺乳动物中调节胆碱能功能的方法，包括给予NRPA化合物或其药学上可接受的盐；以及抗恶心/抗呕吐剂或其药学上可接受的盐；和药学上可接受的载体。NRPA化合物和抗恶心/抗呕吐剂的含量使组合物能够有效调节胆碱能功能或用于治疗炎症性肠病（包括但不限于溃疡性结肠炎、化脓性坏疽和克罗恩病）、肠易激综合症、痉挛性肌张力障碍、慢性疼痛、急性疼痛、乳糜泻、袋炎、血管收缩、焦虑、惊恐障碍、抑郁症、躁郁症、自闭症、睡眠障碍、时差反应、肌萎缩侧索硬化症（ALS）、认知功能障碍、高血压、贪食症、厌食症、肥胖症、心脏心律失常、胃酸过多分泌、溃疡、嗜铬细胞瘤、进行性核上性麻痹、化学依赖和成瘾（例如对尼古丁（和/或烟草制品）、酒精、苯二氮卓、巴比妥类药物、阿片类药物或可卡因的依赖或成瘾）、头痛、偏头痛、中风、创伤性脑损伤（TBI）、强迫症、精神病、亨廷顿舞蹈症、迟发性运动障碍、过动症、阿尔茨海默病的老年性痴呆、帕金森病（PD）、注意力缺陷多动障碍（ADHD）和抽动症。还公开了使用这些组合物的方法。
• Combination treatment for depression and anxiety
  申请人：——

  公开号：US20020049211A1

  公开（公告）日：2002-04-25

  The present invention relates to a method of treating depression or anxiety in a mammal, including a human, by administering to the mammal a CNS-penetrant NK-1 receptor antagonist (e.g., a substance P receptor antagonist) in combination with a 5HT1D receptor antagonist. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a CNS-penetrant NK-1 receptor antagonist and a 5HT 1D receptor antagonist.

  本发明涉及一种治疗哺乳动物（包括人类）的抑郁症或焦虑症的方法，通过给哺乳动物（例如人类）口服中枢神经系统穿透性NK-1受体拮抗剂（例如物质P受体拮抗剂）与5HT1D受体拮抗剂的组合。此外，本发明还涉及含有药学可接受载体、中枢神经系统穿透性NK-1受体拮抗剂和5HT1D受体拮抗剂的制药组合物。
• NK-1 receptor antagonists and eletriptan for the treatment of migraine
  申请人：Pfizer Products Inc.

  公开号：EP1095655A2

  公开（公告）日：2001-05-02

  The present invention relates to a method of treating or preventing migraine in a mammal, including a human, by administering to the mammal eletriptan or a pharmaceutically acceptable salt of eletriptan and an NK-1 receptor antagonist (e.g., a substance P receptor antagonist). It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, eletriptan or a pharmaceutically acceptable salt of eletriptan and an NK-1 receptor antagonist.

  本发明涉及一种治疗或预防哺乳动物（包括人类）偏头痛的方法，其方法是向哺乳动物施用依立普坦或依立普坦的药学上可接受的盐和NK-1受体拮抗剂（如P物质受体拮抗剂）。它还涉及含有药学上可接受的载体、依利普坦或依利普坦的药学上可接受的盐和 NK-1 受体拮抗剂的药物组合物。
• Combination treatment for depression and anxiety containing a CNS-penetrant NK-1 receptor antagonist and an antidepressant or anxiolytic agent
  申请人：Pfizer Products Inc.

  公开号：EP1099446A2

  公开（公告）日：2001-05-16

  The present invention relates to a method of treating depression or anxiety in a mammal, including a human, by administering to the mammal a CNS-penetrant NK-1 receptor antagonist (e.g., a substance P receptor antagonist) in combination with an antidepressant or an anxiolytic agent. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a CNS-penetrant NK-1 receptor antagonist and an anxiolytic agent or antidepressant.

  本发明涉及一种治疗哺乳动物（包括人类）抑郁或焦虑的方法，其方法是向哺乳动物施用中枢神经系统穿透性NK-1受体拮抗剂（如P物质受体拮抗剂）与抗抑郁剂或抗焦虑剂联合使用。它还涉及含有药学上可接受的载体、中枢神经系统穿透性 NK-1 受体拮抗剂和抗焦虑剂或抗抑郁剂的药物组合物。
• Combination, for treating depression and anxiety, containing a 5HT1d receptor antagonist and aCNS penetrant NK-1 receptor antagonist
  申请人：Pfizer Products Inc.

  公开号：EP1186318A2

  公开（公告）日：2002-03-13

  The present invention relates to a method of treating depression or anxiety in a mammal, including a human, by administering to the mammal a CNS-penetrant NK-1 receptor antagonist (e.g., a substance P receptor antagonist) in combination with a 5HT1D receptor antagonist. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a CNS-penetrant NK-1 receptor antagonist and a 5HT1D receptor antagonist.

  本发明涉及一种治疗哺乳动物（包括人类）抑郁症或焦虑症的方法，其方法是向哺乳动物施用中枢神经系统穿透性NK-1受体拮抗剂（如P物质受体拮抗剂）与5HT1D受体拮抗剂。它还涉及含有药学上可接受的载体、中枢神经系统穿透性NK-1受体拮抗剂和5HT1D受体拮抗剂的药物组合物。