8-{4-[4-(1,2-苯并噻唑-3-基)-1-哌嗪基]丁基}-8-氮杂螺[4.5]癸烷-7,9-二酮 | 87691-92-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 8-{4-[4-(1,2-苯并噻唑-3-基)-1-哌嗪基]丁基}-8-氮杂螺[4.5]癸烷-7,9-二酮
• 英文名称: 8-<4-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>butyl>-8-azaspiro<4.5>decane-7,9-dione hydrochloride
• 英文别名: Tiospirone hydrochloride；8-[4-[4-(1,2-Benzothiazol-3-yl)piperazin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione;hydron;chloride；8-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione;hydron;chloride
• CAS: 87691-92-7
• 化学式: C₂₄H₃₂N₄O₂S*ClH
• 分子量: 477.071
• InChiKey: RYAWYTKDKQCORF-UHFFFAOYSA-N

物化性质

• 熔点：
  >218°C (dec.)
• 溶解度：
  DMSO（轻微）、水（轻微、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  4.33
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  85
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-{4-[4-(1,2-苯并噻唑-3-基)-1-哌嗪基]丁基}-8-氮杂螺[4.5]癸烷-7,9-二酮 在 Oxone 、 lithium hexamethyldisilazane 作用下， 以 甲醇 为溶剂， 反应 6.5h， 生成 8-<4-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>butyl>-6-<<<(4-nitrobenzyl)oxy>carbonyl>oxy>-8-azaspiro<4.5>decane-7,9-dione S,S-dioxide
  参考文献：
  名称：

  Synthesis and biological activity of the putative metabolites of the atypical antipsychotic agent tiospirone

  摘要：

  Putative oxidative metabolites of the lead antipsychotic agent tiospirone (1) were synthesized to assist in the identification of the authentic metabolic products found in human urine samples. Thus far, six authentic metabolites have been correlated to the synthetic species. 4a The putative metabolites were further examined in vitro to assess their central nervous system therapeutic potential. SAR analysis of these derivatives indicates that hydroxyl substitution, particularly in the azaspirodecanedione region of the molecule, diminishes the dopamine D-2 affinity of the species without significantly altering the serotonin type-1A and type-2 interactions. In addition, an increase in alpha-1-adrenergic affinity appears to be linked to the attenuation of effects at the dopamine receptors. The biological profile of the 6-hydroxytiospirone metabolite 42 was exemplary in these respects and the in vivo actions of this compound suggest potent antipsychotic potential with a minimal liability for extrapyramidal side effects (EPS). While compound 42 has been unambiguously characterized as an actual human metabolite of tiospirone, the role of 42 in the observed antipsychotic activity of the parent drug, if any, has not yet been determined.

  DOI：

  10.1021/jm00115a024
• 作为产物：
  描述：

  替螺酮 以88的产率得到8-{4-[4-(1,2-苯并噻唑-3-基)-1-哌嗪基]丁基}-8-氮杂螺[4.5]癸烷-7,9-二酮
  参考文献：
  名称：

  Benzisothiazole and benzisoxazole piperazine derivatives

  摘要：

  本文披露了二取代的N,N-哌嗪基衍生物，其中一个取代基是苯并异噻唑-3-基或苯并异恶唑-3-基，另一个是连接到杂环上的烷基，例如氮杂螺[4.5]癸酮、二烷基谷氨酰亚胺、噻唑烷二酮和螺环戊基噻唑烷二酮或丁酰苯酮类似物。这些化合物具有精神药理学特性，8-[4-[4-(1,2-苯并异噻唑-3-基)-1-哌嗪基]丁基]-8-氮杂螺[4.5]癸烷-7,9-二酮是一种具有选择性抗精神病活性的典型实施例。

  公开号：

  US04411901A1

文献信息

• Co-administration of dopamine-receptor binding compounds
  申请人：Fernandes B. Prabhavathi

  公开号：US20070155720A1

  公开（公告）日：2007-07-05

  Methods for treating a patient having neurological, psychotic, and psychiatric disorders are described comprising the steps of administering to the patient an effective amount of a partial and/or full dopamine D 1 receptor agonist, and administering to the patient an effective amount of a dopamine D 2 receptor antagonist. Pharmaceutical compositions comprising a dopamine D 1 receptor agonist and a dopamine D 2 receptor antagonist are also described. The D 1 dopamine receptor agonist and the D 2 dopamine receptor antagonist can be administered to the patient in the same or in a different composition or compositions.

  描述了治疗患有神经、精神和精神障碍的患者的方法，包括向患者施用部分和/或全多巴胺D1受体激动剂的有效量，并向患者施用多巴胺D2受体拮抗剂的有效量。还描述了包含多巴胺D1受体激动剂和多巴胺D2受体拮抗剂的药物组合物。D1多巴胺受体激动剂和D2多巴胺受体拮抗剂可以以相同或不同的组合或组合物形式向患者施用。
• [EN] PRODRUG COMPOSITIONS AND METHODS OF TREATMENT<br/>[FR] COMPOSITIONS DE PROMÉDICAMENT ET PROCÉDÉS DE TRAITEMENT
  申请人：AQUESTIVE THERAPEUTICS INC

  公开号：WO2021087359A1

  公开（公告）日：2021-05-06

  Pharmaceutical compositions include a prodrug of epinephrine are described.

  药物组合物包括表述的肾上腺素前药。
• Multi-functional ionic liquid compositions for overcoming polymorphism and imparting improved properties for active pharmaceutical, biological, nutritional, and energetic ingredients
  申请人：Rogers D. Robin

  公开号：US20070093462A1

  公开（公告）日：2007-04-26

  Disclosed are ionic liquids and methods of preparing ionic liquid compositions of active pharmaceutical, biological, nutritional, and energetic ingredients. Also disclosed are methods of using the compositions described herein to overcome polymorphism, overcome solubility and delivery problems, to control release rates, add functionality, enhance efficacy (synergy), and improve ease of use and manufacture.

  揭示了离子液体及制备活性药物、生物、营养和能量成分的离子液体组合物的方法。还揭示了利用本文描述的组合物的方法，以克服多型性、克服溶解度和输送问题、控制释放速率、增加功能性、增强功效（协同作用）以及改善易用性和制造工艺。
• [EN] DREADD ACTUATORS<br/>[FR] ACTIONNEURS DREADD
  申请人：US HEALTH

  公开号：WO2019157083A1

  公开（公告）日：2019-08-15

  Disclosed is a compound of formula (I) in which R1, R2, and R3 are as described herein. Also provided are pharmaceutical compositions comprising the compound of formula (I) and methods of using the compound of formula (I), including a method of treating a disease or disorder and a method for effectuating a G-protein coupled receptor (GPCR)-mediated response in a subject.

  公开了一种化合物的化学式(I)，其中R1、R2和R3如本文所述。还提供了包含化合物的药物组合物的制剂(I)和使用化合物的方法(I)，包括治疗疾病或紊乱的方法以及在受试者中实现G蛋白偶联受体(GPCR)介导的反应的方法。
• COMPOSITIONS AND METHODS FOR TREATMENT OF VIRAL DISEASES
  申请人：Johansen Lisa M.

  公开号：US20100009970A1

  公开（公告）日：2010-01-14

  The present invention features compositions, methods, and kits useful in the treatment of viral diseases. In certain embodiments, the viral disease is caused by a single stranded RNA virus, a flaviviridae virus, or a hepatic virus. In particular embodiments, the viral disease is viral hepatitis (e.g., hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E) and the agent or combination of agents includes sertraline, a sertraline analog, UK-416244, or a UK-416244 analog. Also featured are screening methods for identification of novel compounds that may be used to treat a viral disease.

  本发明涉及用于治疗病毒性疾病的组合物、方法和试剂盒。在某些实施方式中，病毒性疾病是由单链RNA病毒、黄病毒科病毒或肝病毒引起的。在特定实施方式中，病毒性疾病是病毒性肝炎（例如甲型肝炎、乙型肝炎、丙型肝炎、丁型肝炎、戊型肝炎），药剂或药剂组合包括舍曲林、舍曲林类似物、UK-416244或UK-416244类似物。还包括用于鉴定可用于治疗病毒性疾病的新化合物的筛选方法。