盐酸沃替西汀杂质6 | 1293342-97-8

• 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: 盐酸沃替西汀杂质6
• 英文名称: 1-[2-(3,4-dimethylphenylsulfanyl)phenyl]piperazine hydrochloride
• 英文别名: 1-(2-((3,4-Dimethylphenyl)thio)phenyl)piperazine hydrochloride；1-[2-(3,4-dimethylphenyl)sulfanylphenyl]piperazine;hydrochloride
• CAS: 1293342-97-8
• 化学式: C₁₈H₂₂N₂S*ClH
• 分子量: 334.913
• InChiKey: VHKBDODTXKHVJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.29
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  40.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-[2-(3,4-dimethylphenylsulfanyl)phenyl]piperazine-1-carboxylic acid tert-butyl ester 在 盐酸 、 甲醇 作用下， 以 乙醚 为溶剂， 生成 盐酸沃替西汀杂质6
  参考文献：
  名称：

  Discovery of 1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): A Novel Multimodal Compound for the Treatment of Major Depressive Disorder

  摘要：

  The synthesis and structure-activity relationship of a novel series of compounds with combined effects on 5-HT3A and 5-HT1A receptors and on the serotonin (5-HT) transporter (SERT) are described. Compound 5m (Lu AA21004) was the lead compound, displaying high affinity for recombinant human 5-HT1A (K-i = 15 nM), 5-HT1B (K-i = 33 nM), 5-HT3A (K-i = 3.7 nM), 5-HT7 (K-i = 19 nM), and noradrenergic beta(1) (K-i = 46 nM) receptors, and SERT (K-i = 1.6 nM). Compound 5m displayed antagonistic properties at 5-HT3A and 5-HT7 receptors, partial agonist properties at 5-HT1B receptors, agonistic properties at 5-HT1A receptors, and potent inhibition of SERT. In conscious rats, 5m significantly increased extracellular 5-HT levels in the brain after acute and 3 days of treatment. Following the 3-day treatment (5 or 10 (mg/kg)/day) SERT occupancies were only 43% and 57%, respectively. These characteristics indicate that 5m is a novel multimodal serotonergic compound, and 5m is currently in clinical development for major depressive disorder.

  DOI：

  10.1021/jm101459g

文献信息

• Discovery of 1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): A Novel Multimodal Compound for the Treatment of Major Depressive Disorder
  作者：Benny Bang-Andersen、Thomas Ruhland、Morten Jørgensen、Garrick Smith、Kristen Frederiksen、Klaus Gjervig Jensen、Huailing Zhong、Søren Møller Nielsen、Sandra Hogg、Arne Mørk、Tine Bryan Stensbøl

  DOI：10.1021/jm101459g

  日期：2011.5.12

  The synthesis and structure-activity relationship of a novel series of compounds with combined effects on 5-HT3A and 5-HT1A receptors and on the serotonin (5-HT) transporter (SERT) are described. Compound 5m (Lu AA21004) was the lead compound, displaying high affinity for recombinant human 5-HT1A (K-i = 15 nM), 5-HT1B (K-i = 33 nM), 5-HT3A (K-i = 3.7 nM), 5-HT7 (K-i = 19 nM), and noradrenergic beta(1) (K-i = 46 nM) receptors, and SERT (K-i = 1.6 nM). Compound 5m displayed antagonistic properties at 5-HT3A and 5-HT7 receptors, partial agonist properties at 5-HT1B receptors, agonistic properties at 5-HT1A receptors, and potent inhibition of SERT. In conscious rats, 5m significantly increased extracellular 5-HT levels in the brain after acute and 3 days of treatment. Following the 3-day treatment (5 or 10 (mg/kg)/day) SERT occupancies were only 43% and 57%, respectively. These characteristics indicate that 5m is a novel multimodal serotonergic compound, and 5m is currently in clinical development for major depressive disorder.