螺哌隆盐酸盐 | 2022-29-9

• 中文名称: 螺哌隆盐酸盐
• 英文名称: Spiperone hydrochloride
• 英文别名: 8-[4-(4-fluorophenyl)-4-oxobutyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one;hydrochloride
• CAS: 2022-29-9
• 化学式: C23H27ClFN3O2
• 分子量: 431.9
• InChiKey: QUIKMLCZZMOBLH-UHFFFAOYSA-N

物化性质

• 溶解度：
  在 DMSO 中溶解度为 100 mM

计算性质

• 辛醇/水分配系数(LogP)：
  3.64
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  5

制备方法与用途

生物活性

Spiperone hydrochloride (Spiroperidol hydrochloride) 是一种选择性的多巴胺 D2 受体 (D2，D3，D4，D1 和 D5 受体的 Ki 值分别为 0.06 nM，0.6 nM，0.08 nM，~350 nM，~3500 nM) 和 5-HT2A/5-HT1A 受体 (Ki 为1 nM/49 nM) 拮抗剂。Spiperone hydrochloride 也是一种选择性的 α1B-肾上腺素受体 (α1B-adrenoceptor) 拮抗剂。Spiperone hydrochloride 激活钙激活的氯离子通道 (CaCC)。抗精神病和抗炎作用。

靶点

D 2 Receptor 0.06 nM (Ki)

D 1 Receptor ~350 nM (Ki)

D 3 Receptor 0.6 nM (Ki)

D 4 Receptor 0.08 nM (Ki)

D 5 Receptor ~3500 nM (Ki)

5-HT 2A Receptor 1 nM (Ki)

5-HT 1A Receptor 49 nM (Ki)

α1B-adrenoceptor

Calcium-activated chloride channel

体外研究

Spiperone is a potent intracellular Ca ²⁺ enhancer (EC ₅₀ =9.3 μM) and stimulates intracellular Ca ²⁺ through a protein tyrosine kinase-coupled phospholipase C-dependent pathway, which results in increased secretion of Cl ^- in Calu-3 and CFBE41o ^- cell monolayers.
Spiperone significantly decreases the production of nitric oxide in lipopolysaccharide-stimulated BV-2 microglia cells, primary microglia and primary astrocyte cultures. Spiperone also significantly inhibits nitric oxide production in ATP-stimulated primary microglia cultures. Spiperone markedly decreases the production of TNF-α in BV-2 microglia cells. Spiperone attenuates the expression of inducible nitric oxide synthase and proinflammatory cytokines such as IL-1β and TNF-α at mRNA levels in BV-2 microglia cells.

体内研究

Spiperone (1.5 mg/kg; intraperitoneal injection; on days 1, 3, 6, 7, and 13-21; C57Bl/6 mice) treatment reduces infiltration of the alveolar interstitium and alveolar ducts with inflammatory cells and prevents the growth of the connective tissue in the parenchyma of Bleomycin lungs.

Animal Model:	C57Bl/6 mice (7-8-week-old) induced pulmonary fibrosis by Bleomycin
Dosage:	1.5 mg/kg
Administration:	Intraperitoneal injection; on days 1, 3, 6, 7, and 13-21
Result:	Reduced infiltration of the alveolar interstitium and alveolar ducts with inflammatory cells and prevented the growth of the connective tissue in the parenchyma of bleomycin lungs.

文献信息

• Novel 1-Heteroaryl-3-Azabicyclo[3.1.0]Hexanes Methods For Their Preparation And Their Use As Medicaments
  申请人：NEUROVANCE, Inc.

  公开号：US20140303207A1

  公开（公告）日：2014-10-09

  The invention provides novel 1-heteroaryl-3-azabicyclo[3.1.0]hexanes, and related processes and intermediates for preparing these compounds, as well as compositions and methods employing these compounds for the treatment and/or prevention of central nervous system (CNS) disorders, including but not limited to depression and anxiety.

  本发明提供了新型的1-杂芳基-3-氮杂双环[3.1.0]己烷化合物，以及用于制备这些化合物的相关过程和中间体，还包括使用这些化合物的组合物和方法，用于治疗和/或预防中枢神经系统（CNS）疾病，包括但不限于抑郁症和焦虑症。
• [EN] PREPARATION AND USE OF (+)-1-(3,4-DICHLOROPHENYL)-3-AZABICYCLO[3.1.0]HEXANE IN THE TREATMENT OF CONDITIONS AFFECTED BY MONOAMINE NEUROTRANSMITTERS<br/>[FR] PRÉPARATION ET UTILISATION DU (+)-1-(3,4-DICHLOROPHÉNYL)-3-AZABICYCLO- [3.1.0]HEXANE DANS LE TRAITEMENT DES PATHOLOGIES AFFECTÉES PAR LES NEUROTRANSMETTEURS DE TYPE MONOAMINE
  申请人：EUTHYMIC BIOSCIENCE INC

  公开号：WO2012075473A1

  公开（公告）日：2012-06-07

  The present invention relates to (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and pharmaceutically acceptable active salts, polymorphs, glycosylated derivatives, metabolites, solvates, hydrates, and/or prodrugs of (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and their use alone or in combination with additional psychotherapeutic compositions in the treatment of conditions affected by monoamine neurotransmitters, including treatment of refractory individuals.

  本发明涉及(+)-1-(3,4-二氯苯基)-3-氮杂双环[3.1.0]己烷及其药用可接受的活性盐、多型、糖基化衍生物、代谢物、溶剂合物、水合物和/或前药，以及其单独使用或与其他心理治疗组合物结合在一起用于治疗受单胺神经递质影响的疾病的用途，包括治疗难治性个体。
• USE OF AMITIFADINE, (+)-1-(3,4-DICHLOROPHENYL)-3-AZABICYCLO[3.1.0]HEXANE IN METHODS AND COMPOSITIONS WITH ENHANCED EFFICACY AND REDUCED METABOLIC SIDE EFFECTS AND TOXICITY FOR TREATMENT OF DEPRESSION AND OTHER CENTRAL NERVOUS SYSTEM DISORDERS AND CONDITIONS AFFECTED BY MONOAMINE NEUROTRANSMITTERS
  申请人：McKinney Anthony Alexander

  公开号：US20160346249A1

  公开（公告）日：2016-12-01

  The present invention relates to (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and pharmaceutically acceptable active salts, polymorphs, glycosylated derivatives, metabolites, solvates, hydrates, and/or prodrugs of (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and their use alone or in combination with additional psychotherapeutic compositions in the treatment of conditions affected by monoamine neurotransmitters, including treatment of refractory individuals. (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane compositions are metabolized by either or both MAO-A or cytochrome P450 enzymes and thus are effective in the treatment of individuals with cytochrome P450 polymorphisms or who are taking other medications that affect the cytochrome P450 pathway.

  本发明涉及（+）-1-（3,4-二氯苯基）-3-氮杂双环[3.1.0]己烷及其药用可接受的活性盐、多晶形态、糖基化衍生物、代谢物、溶剂合物、水合物和/或前药，以及其单独使用或与额外的精神疗法组合一起治疗受单胺神经递质影响的疾病，包括难治性个体的治疗。 （+）-1-（3,4-二氯苯基）-3-氮杂双环[3.1.0]己烷组合物被MAO-A或细胞色素P450酶中的任一或两者代谢，因此对患有细胞色素P450多态性或正在服用影响细胞色素P450途径的其他药物的个体进行治疗是有效的。
• [EN] USE OF (1R,5S)-(+)-1-(NAPHTHALEN-2-YL)-3-AZABICYCLO{3.1.0}HEXANE IN THE TREATMENT OF CONDITIONS AFFECTED BY MONOAMINE NEUROTRANSMITTERS<br/>[FR] UTILISATION DE (LR,5S)-(+)-L-(NAPHTHALÈN-2-YL)-3-AZABICYCLO[3.1.0]HEXANE DANS LE CADRE DU TRAITEMENT D'AFFECTIONS ASSOCIÉES AUX NEUROTRANSMETTEURS MONO-AMINE
  申请人：NEUROVANCE INC

  公开号：WO2013019271A1

  公开（公告）日：2013-02-07

  The present invention relates to (lR,5S)-(+)-l-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane and pharmaceutical compositions thereof, and methods employing their use in the treatment of conditions affected by monoamine neurotransmitters, including ADHD and substance abuse.

  本发明涉及（lR,5S）-（+）-1-（萘基）-3-氮杂双环[3.1.0]己烷及其制药组合物，以及使用它们治疗受单胺神经递质影响的疾病，包括注意力缺陷多动障碍和物质滥用的方法。
• (-)-1-(3,4-Dichlorophenyl)-3-azabicyclo[3.1.0]hexane, compositions thereof, and uses as a dopamine-reuptake inhibitor
  申请人：——

  公开号：US20030045567A1

  公开（公告）日：2003-03-06

  The present invention relates to (−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and pharmaceutically acceptable salts thereof, compositions comprising (−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof, and methods for treating or preventing a disorder alleviated by inhibiting dopamine reuptake. In one embodiment, the disorder is attention-deficit disorder, depression, obesity, Parkinson's disease, a tic disorder, or an addictive disorder. The (−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is preferably substantially free of its corresponding (+)-enantiomer.

  本发明涉及(−)-1-(3,4-二氯苯基)-3-氮杂双环[3.1.0]己烷及其药学上可接受的盐，包含(−)-1-(3,4-二氯苯基)-3-氮杂双环[3.1.0]己烷或其药学上可接受的盐的组合物，以及用于治疗或预防通过抑制多巴胺再摄取缓解的疾病的方法。在某些实施例中，该疾病为注意力缺陷障碍、抑郁症、肥胖症、帕金森氏病、抽动障碍或成瘾性疾病。所述(−)-1-(3,4-二氯苯基)-3-氮杂双环[3.1.0]己烷或其药学上可接受的盐最好基本上不含其相应的(+)对映体。