3-chloro-4,5-dihydro-4-(4-(4-((4-methyl)pyrimidin-2-yl)-1,2,3,6-tetrahydropyridin-1-yl)butyl)-1,4-benzoxazepin-5-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 3-chloro-4,5-dihydro-4-(4-(4-((4-methyl)pyrimidin-2-yl)-1,2,3,6-tetrahydropyridin-1-yl)butyl)-1,4-benzoxazepin-5-one
• 英文别名: 3-chloro-4,5-dihydro-4-(4-(4-((4-methyl)pyrimidin-2-yl)-1,2,5,6-tetrahydropyridin-1-yl)butyl)-1,4-benzoxazepin-5-one；3-chloro-4,5-dihydro-4-(4-{4-[(4-methyl)-2-pyrimidinyl]-1,2,3,6-tetrahydropyridin-1-yl}butyl)-1,4-benzoxazepin-5-one；3-chloro-4-[4-[4-(4-methylpyrimidin-2-yl)-3,6-dihydro-2H-pyridin-1-yl]butyl]-1,4-benzoxazepin-5-one
• 化学式: C₂₃H₂₅ClN₄O₂
• 分子量: 424.93
• InChiKey: HSQVLKIYZGPORB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-amidinopyridine hydrochloride 在 sodium tetrahydroborate 、 1-氯乙基氯甲酸酯 、 三乙胺 、 sodium iodide 作用下， 以 1,4-二氧六环 、 乙醇 、 1,2-二氯乙烷 、 乙腈 为溶剂， 生成 3-chloro-4,5-dihydro-4-(4-(4-((4-methyl)pyrimidin-2-yl)-1,2,3,6-tetrahydropyridin-1-yl)butyl)-1,4-benzoxazepin-5-one
  参考文献：
  名称：

  New piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives as selective 5-HT1A receptor agonists with highly potent anti-ischemic effects

  摘要：

  A series of new piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives were synthesized. Among these compounds, 4-methyl-2-(1,2,3,6-tetrahydropyridin-4-yl)pyrimidine derivative 23 (SUN N5147) exhibited sub-nanomolar affinity for 5-HT1A receptor with 1000-fold selectivity over both dopamine D-2 and alpha(1)-adrenergic receptors and remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.04.059

文献信息

• Benzoxazepine derivatives and their salts and medicaments containing the same
  申请人：Suntory Limited

  公开号：US06187769B1

  公开（公告）日：2001-02-13

  A benzoxazepine derivative having the general formula (I) and its salts and medicaments containing the same as effective ingredients: wherein, n is an integer of 2 to 5, R1 indicates a hydrogen atom, halogen atom, C1 to C4 lower alkyl group, C1 to C4 lower alkoxyalkyl group, C1 to C4 halogenoalkyl group, cyano group, or ester group, R2 indicates a hydrogen atom, halogen atom, C1 to C4 lower alkyl group, C1 to C4 lower alkoxy group, or hydroxy group, a dotted line indicates the presence or absence of a binding bond, W indicates C, CH, or CH2 or a nitrogen atom, provided that, when W is a nitrogen atom, Z is bonded to W and the dotted line indicates the absence of a bond, and Z indicates an unsubstituted or substituted aromatic hydrocarbon ring group or an unsubstituted or substituted heterocyclic group). This benzoxazepine derivative and its salts are useful as medicaments for the treatment of anxiety neurosis, phobias, obsessive-compulsive disorders, schizophrenia, post-cardiac trauma stress, depression, psychosomatic and other psychoneurotic disorders, eating disorders, menopausal disorders, infantile autism and also emesis or disorders involving the cerebral circulatory system accompanying cerebral infarction and cerebral hemorrhage.

  一种具有通式（I）的苯并噁唑啉衍生物及其盐和含有相同有效成分的药物： 其中，n为2至5的整数，R1表示氢原子、卤原子、C1至C4的低碳基团、C1至C4的低碳氧基碳基团、C1至C4的卤代烷基团、氰基或酯基，R2表示氢原子、卤原子、C1至C4的低碳基团、C1至C4的低碳氧基团或羟基，虚线表示结合键的存在或缺失，W表示C、CH或CH2或氮原子，但当W为氮原子时，Z与W结合，虚线表示缺少结合，Z表示未取代或取代的芳香烃环基团或未取代或取代的杂环基团）。 这种苯并噁唑啉衍生物及其盐可用作治疗焦虑神经症、恐惧症、强迫症、精神分裂症、心脏创伤后应激、抑郁症、心身疾病和其他精神神经病性障碍、进食障碍、更年期障碍、婴儿孤独症以及伴有脑梗死和脑出血的脑循环系统紊乱或呕吐症的药物。
• AGENT FOR IMPROVING MOTOR COMPLICATIONS OR PSYCHIATRIC SYMPTOMS IN PARKINSON'S DISEASE
  申请人：Asubio Pharma Co., Ltd.

  公开号：EP2213290A1

  公开（公告）日：2010-08-04

  A drug containing a compound having the formula (I): or a pharmacologically acceptable salt thereof or their hydrates, which alleviates motor complications associated with a treatment with levodopa for Parkinson's disease, delays the onset of motor complications associated with a treatment with levodopa, and inhibiting or delaying the advance of symptoms of Parkinson's disease is provided. The compound having the formula (I) has a serotonin 1A receptor partial agonist action, does not have an antagonist action against dopamine D2 receptors, has an agonist action against dopamine D3 receptors, has an effect of alleviation and delay of onset of motor complications associated with repeated doses of levodopa and, further, is also effective against associated with psychiatric symptoms in advanced stage Parkinson's disease patients.

  一种含有式(I)化合物的药物： 或其药理学上可接受的盐或它们的水合物的药物，该药物可减轻与左旋多巴治疗帕金森病相关的运动并发症，延缓与左旋多巴治疗相关的运动并发症的发生，抑制或延缓帕金森病症状的发展。具有式（I）的化合物具有5-羟色胺1A受体部分激动作用，对多巴胺D2受体无拮抗作用，对多巴胺D3受体有激动作用，具有缓解和延迟与重复剂量左旋多巴治疗相关的运动并发症发作的作用，此外，还对晚期帕金森病患者的相关精神症状有效。
• PROCESS OF PRODUCTION OF 4-SUBSTITUTED-3-HALOGENO-1,4-BENZOXAZEPINE DERIVATIVE AND SALTS THEREOF
  申请人：SUNTORY LIMITED

  公开号：EP0925288B1

  公开（公告）日：2002-09-25
• BENZOXAZEPINE DERIVATIVES, SALTS THEREOF, AND DRUGS CONTAINING THE SAME
  申请人：SUNTORY LIMITED

  公开号：EP0755930B1

  公开（公告）日：2002-07-31
• DRUG FOR ALLEVIATING MOTOR COMPLICATIONS OR PSYCHIATRIC SYMPTOMS OF PARKINSON'S DISEASE
  申请人：Tani Yoshihiro

  公开号：US20100204202A1

  公开（公告）日：2010-08-12

  A drug containing a compound having the formula (I): or a pharmacologically acceptable salt thereof or their hydrates, which alleviates motor complications associated with a treatment with levodopa for Parkinson's disease, delays the onset of motor complications associated with a treatment with levodopa, and inhibiting or delaying the advance of symptoms of Parkinson's disease is provided. The compound having the formula (I) has a serotonin 1A receptor partial agonist action, does not have an antagonist action against dopamine D2 receptors, has an agonist action against dopamine D3 receptors, has an effect of alleviation and delay of onset of motor complications associated with repeated doses of levodopa and, further, is also effective against associated with psychiatric symptoms in advanced stage Parkinson's disease patients.