960203-27-4

• 常用中文名：氢溴酸沃替西汀
• 常用英文名：Vortioxetine (Lu AA21004) HBr
• CAS号：960203-27-4
• 分子式：C₁₈H₂₃BrN₂S
• 分子量：379.358
• 相关类别： 原料药 神经系统用药 抗焦虑药
• 发布时间：2018-06-22 15:49:05
• 更新时间：2024-01-02 12:25:38
• Vortioxetine hydrobromide 是5-HT1A,5-HT1B,5-HT3A,5-HT7 受体 和5-羟色胺转运体 (SERT) 的抑制剂,其Ki值分别为 15 nM,33 nM,3.7 nM,19 nM 和 1.6 nM。

名称

• 中文名: 沃替西汀氢溴酸盐
• 英文名: vortioxetine hydrobromide
• 英文别名: Brintellix; 1-{2-[(2,4-Dimethylphenyl)sulfanyl]phenyl}piperazine hydrobromide (1:1); Piperazine, 1-[2-[(2,4-dimethylphenyl)thio]phenyl]-, hydrobromide (1:1); UNII:TKS641KOAY; VORTIOXETINE HBr; Vortioxetine hydrobromide; vortioxetine monohydrobromide; 1-(2-((2,4-Dimethylphenyl)sulfanyl)phenyl)piperazine monohydrobromide; 1-[2-[(2,4-Dimethylphenyl)thio]phenyl]piperazinehydrobromide; 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine hydrobromide; Vortioxetine (hydrobromide)

物化性质

• 分子式: C₁₈H₂₃BrN₂S
• 分子量: 379.358
• 精确质量: 378.076538
• PSA: 40.57000
• LogP: 5.21610
• 储存条件: -20°C

生物活性

• 描述: Vortioxetine hydrobromide 是5-HT1A,5-HT1B,5-HT3A,5-HT7 受体 和5-羟色胺转运体 (SERT) 的抑制剂,其Ki值分别为 15 nM,33 nM,3.7 nM,19 nM 和 1.6 nM。
• 相关类别:
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> 5-HT受体
  信号通路 >> 神经信号通路 >> 5-HT受体
  信号通路 >> 神经信号通路 >> 5-羟色胺转运蛋白
  研究领域 >> 神经疾病
• 靶点:

  5-HT1A Receptor:15 nM (Ki)

  5-HT1B Receptor:33 nM (Ki)

  5-HT3A Receptor:3.7 nM (Ki)

  5-HT7 Receptor:19 nM (Ki)

  SERT:1.6 nM (Ki)

• 体外研究: Vortioxetine(化合物5m)是一种多模式5-羟色胺能药物,抑制5-HT1A,5-HT1B,5-HT3A,5-HT7受体和SERT,Ki值分别为15 nM,33 nM,3.7 nM,19 nM和1.6 nM 。 Vortioxetine对5-HT3A和5-HT7受体具有拮抗特性,对5-HT1B受体具有部分激动剂特性,对5-HT1A受体具有激动特性,对SERT有强烈的抑制作用[1]。 Vortioxetine是部分h5-HT 1B受体激动剂,使用基于全细胞cAMP的测定法,EC50为460nM,内在活性为22％。 Vortioxetine与r5-HT 7受体结合,Ki值为200 nM,是体外全细胞cAMP检测中r5-HT7受体的功能性拮抗剂,IC50为2μM[5]。
• 体内研究: Vortioxetine(Lu AA21004)在皮下给药后占据r5-HT1B受体和rSERT(分别为ED50 = 3.2和0.4mg/kg),并且是5-HT3受体拮抗剂[6]。在治疗21天后,Vortioxetine显着增加细胞增殖和细胞存活,并刺激海马齿状回亚颗粒区中未成熟颗粒细胞的成熟[3]。 Vortioxetine不会引起认知或精神运动障碍[4]。
• 参考文献:

  [1]. Bang-Andersen B, et al. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21.

  [2]. Guilloux JP, et al. Antidepressant and anxiolytic potential of the multimodal antidepressant vortioxetine (Lu AA21004) assessed by behavioural and neurogenesis outcomes in mice. Neuropharmacology. 2013 May 28;73C:147-159.

  [3]. Theunissen EL, et al. A randomized trial on the acute and steady-state effects of a new antidepressant, vortioxetine (Lu AA21004), on actual driving and cognition. Clin Pharmacol Ther. 2013 Jun;93(6):493-501.

  [4]. Rothschild AJ, Mahableshwarkar AR, Jacobsen P, Vortioxetine (Lu AA21004) 5mg in generalized anxiety disorder: results of an 8-week randomized, double-blind, placebo-controlled clinical trial in the United States. Eur Neuropsychopharmacol. 2012 Dec;22(12):858-66.

  [5]. Mork A, et al. Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. J Pharmacol Exp Ther. 2012 Mar;340(3):666-75.

合成路线

110-85-0 4214-28-2 6320-02-1 ~84% 960203-27-4

文献：H. LUNDBECK A/S; CHRISTENSEN, Kim, Lasse Patent: WO2013/102573 A1, 2013 ; Location in patent: Page/Page column 13; 14 ;

508233-74-7 ~81% 960203-27-4

文献：H. LUNDBECK A/S Patent: WO2008/113359 A2, 2008 ; Location in patent: Page/Page column 16 ; WO 2008/113359 A2

960203-28-5 ~% 960203-27-4

文献：H. LUNDBECK A/S Patent: WO2008/113359 A2, 2008 ; Location in patent: Page/Page column 17 ; WO 2008/113359 A2

110-85-0 583-55-1 13616-82-5 ~83% 960203-27-4

文献：H. LUNDBECK A/S; CHRISTENSEN, Kim, Lasse Patent: WO2013/102573 A1, 2013 ; Location in patent: Page/Page column 14; 15 ;

960203-42-3 ~% 960203-27-4

文献：H. LUNDBECK A/S Patent: WO2007/144005 A1, 2007 ; Location in patent: Page/Page column 44-45 ; WO 2007/144005 A1

960203-39-8 ~% 960203-27-4

文献：H. LUNDBECK A/S Patent: WO2008/113359 A2, 2008 ; Location in patent: Page/Page column 18 ; WO 2008/113359 A2

1393733-77-1 ~% 960203-27-4 1393644-67-1

文献：Uldam, Henriette Kold; Juhl, Martin; Pedersen, Henrik; Dalgaard, Lars Drug Metabolism and Disposition, 2011 , vol. 39, # 12 p. 2264 - 2274

1393733-76-0 ~% 960203-27-4 1393644-67-1

文献：Uldam, Henriette Kold; Juhl, Martin; Pedersen, Henrik; Dalgaard, Lars Drug Metabolism and Disposition, 2011 , vol. 39, # 12 p. 2264 - 2274

1019453-85-0 ~% 960203-27-4 1393644-67-1

文献：Uldam, Henriette Kold; Juhl, Martin; Pedersen, Henrik; Dalgaard, Lars Drug Metabolism and Disposition, 2011 , vol. 39, # 12 p. 2264 - 2274