1211866-85-1

• 常用中文名：TC-N 1752
• 常用英文名：TC-N 1752
• CAS号：1211866-85-1
• 分子式：C₂₅H₂₇F₃N₆O₃
• 分子量：516.52
• 相关类别： 信号通路 跨膜转运 钠通道
• 发布时间：2017-10-03 13:21:37
• 更新时间：2024-01-22 05:26:27
• TC-N 1752是一种口服有效的Nav1抑制剂。7,hNav1的IC50分别为0.17μM、0.3μM、0.4μM、1.1μM和2.2μM。7,hNav1。3,hNav1。4,hNaV1。5和rNav1。分别为8。TC-N 1752也抑制河豚毒素敏感的钠通道。TC-N 1752在福尔马林疼痛模型中显示镇痛效果[1][2][3]。

名称

• 中文名: TC-N1752
• 英文名: N-(2-Methyl-3-{[4-(4-{[4-(trifluoromethoxy)benzyl]oxy}-1-piperidi nyl)-1,3,5-triazin-2-yl]amino}phenyl)acetamide
• 英文别名: Cyclohexanamine,N-(2-methyl-2-propenylidene)-,(E); N-(2-methyl-3-(4-(4-(4-(trifluoromethoxy)benzyloxy)piperidin-1-yl)-1,3,5-triazin-2-ylamino)phenyl)acetamide; N-(2-methyl-2-propen-1-ylidene)cyclohexylamine; Cyclohexanamine,N-(2-methyl-2-propenylidene)

物化性质

• 密度: 1.37±0.1 g/cm3(Predicted)
• 分子式: C₂₅H₂₇F₃N₆O₃
• 分子量: 516.52
• 精确质量: 516.21000
• PSA: 108.22000
• LogP: 5.10260
• 储存条件: 2-8°C

生物活性

• 描述: TC-N 1752是一种口服有效的Nav1抑制剂。7,hNav1的IC50分别为0.17μM、0.3μM、0.4μM、1.1μM和2.2μM。7,hNav1。3,hNav1。4,hNaV1。5和rNav1。分别为8。TC-N 1752也抑制河豚毒素敏感的钠通道。TC-N 1752在福尔马林疼痛模型中显示镇痛效果[1][2][3]。
• 相关类别:
  信号通路 >> 跨膜转运 >> 钠通道
  研究领域 >> 神经疾病
• 靶点:

  hNav1.7:0.17 μM (IC50)

  hNav1.3:0.3 μM (IC50)

  hNav1.4:0.4 μM (IC50)

  hNav1.5:1.1 μM (IC50)

  hNav1.8:0.1 μM (IC50)

• 体外研究: TC-N 1752(化合物52)状态依赖性地抑制Nav1。7,20%失活通道的IC50为170 nM,完全非激活通道的IC50为3.6μM[1]。TC-N 1752抑制hNav1。7,hNav1。8,hNav1。9,rNav1。9和mNav1。9,IC50分别为0.2、0.1、1.6、0.5和1.4μM[2]。
• 体内研究: TC-N 1752(化合物52)(3-30 mg/kg；p.o.)在福尔马林模型中呈剂量依赖性显示镇痛作用[1]。TC-N 1752(3-30 mg/kg；p.o.)降低炎症引起的热痛觉过敏[3]。TC-N 1752(5 mg/mL；500μL；静脉注射)减弱完全弗氏佐剂(CFA)诱导的C-纤维伤害感受器致敏作用[3]。动物模型：在大鼠体内注射福尔马林[1]剂量：3,10,20,30 mg/kg给药：在福尔马林前120分钟给药结果：从3 mg/kg剂量开始显示镇痛效果,20 mg/kg剂量完全有效。
• 参考文献:

  [1]. Bregman H, et, al. Identification of a potent, state-dependent inhibitor of Nav1.7 with oral efficacy in the formalin model of persistent pain. J Med Chem. 2011 Jul 14;54(13):4427-45.

  [2]. Lin Z, et, al. Biophysical and Pharmacological Characterization of Nav1.9 Voltage Dependent Sodium Channels Stably Expressed in HEK-293 Cells. PLoS One. 2016 Aug 24;11(8):e0161450.

  [3]. Matson DJ, et, al. Inhibition of Inactive States of Tetrodotoxin-Sensitive Sodium Channels Reduces Spontaneous Firing of C-Fiber Nociceptors and Produces Analgesia in Formalin and Complete Freund's Adjuvant Models of Pain. PLoS One. 2015 Sep 17;10(9):e0138140.

合成路线

1211876-60-6 1211875-20-5 ~77% 1211866-85-1

文献：Bregman, Howard; Berry, Loren; Buchanan, John L.; Chen, April; Du, Bingfan; Feric, Elma; Hierl, Markus; Huang, Liyue; Immke, David; Janosky, Brett; Johnson, Danielle; Li, Xingwen; Ligutti, Joseph; Liu, Dong; Malmberg, Annika; Matson, David; McDermott, Jeff; Miu, Peter; Nguyen, Hanh Nho; Patel, Vinod F.; Waldon, Daniel; Wilenkin, Ben; Zheng, Xiao Mei; Zou, Anruo; McDonough, Stefan I.; Dimauro, Erin F. Journal of Medicinal Chemistry, 2011 , vol. 54, # 13 p. 4427 - 4445

287952-21-0 ~% 1211866-85-1

文献：Bregman, Howard; Berry, Loren; Buchanan, John L.; Chen, April; Du, Bingfan; Feric, Elma; Hierl, Markus; Huang, Liyue; Immke, David; Janosky, Brett; Johnson, Danielle; Li, Xingwen; Ligutti, Joseph; Liu, Dong; Malmberg, Annika; Matson, David; McDermott, Jeff; Miu, Peter; Nguyen, Hanh Nho; Patel, Vinod F.; Waldon, Daniel; Wilenkin, Ben; Zheng, Xiao Mei; Zou, Anruo; McDonough, Stefan I.; Dimauro, Erin F. Journal of Medicinal Chemistry, 2011 , vol. 54, # 13 p. 4427 - 4445

50824-05-0 ~% 1211866-85-1

文献：Bregman, Howard; Berry, Loren; Buchanan, John L.; Chen, April; Du, Bingfan; Feric, Elma; Hierl, Markus; Huang, Liyue; Immke, David; Janosky, Brett; Johnson, Danielle; Li, Xingwen; Ligutti, Joseph; Liu, Dong; Malmberg, Annika; Matson, David; McDermott, Jeff; Miu, Peter; Nguyen, Hanh Nho; Patel, Vinod F.; Waldon, Daniel; Wilenkin, Ben; Zheng, Xiao Mei; Zou, Anruo; McDonough, Stefan I.; Dimauro, Erin F. Journal of Medicinal Chemistry, 2011 , vol. 54, # 13 p. 4427 - 4445

65999-76-0 ~% 1211866-85-1

文献：Bregman, Howard; Berry, Loren; Buchanan, John L.; Chen, April; Du, Bingfan; Feric, Elma; Hierl, Markus; Huang, Liyue; Immke, David; Janosky, Brett; Johnson, Danielle; Li, Xingwen; Ligutti, Joseph; Liu, Dong; Malmberg, Annika; Matson, David; McDermott, Jeff; Miu, Peter; Nguyen, Hanh Nho; Patel, Vinod F.; Waldon, Daniel; Wilenkin, Ben; Zheng, Xiao Mei; Zou, Anruo; McDonough, Stefan I.; Dimauro, Erin F. Journal of Medicinal Chemistry, 2011 , vol. 54, # 13 p. 4427 - 4445

109384-19-2 ~% 1211866-85-1

文献：Bregman, Howard; Berry, Loren; Buchanan, John L.; Chen, April; Du, Bingfan; Feric, Elma; Hierl, Markus; Huang, Liyue; Immke, David; Janosky, Brett; Johnson, Danielle; Li, Xingwen; Ligutti, Joseph; Liu, Dong; Malmberg, Annika; Matson, David; McDermott, Jeff; Miu, Peter; Nguyen, Hanh Nho; Patel, Vinod F.; Waldon, Daniel; Wilenkin, Ben; Zheng, Xiao Mei; Zou, Anruo; McDonough, Stefan I.; Dimauro, Erin F. Journal of Medicinal Chemistry, 2011 , vol. 54, # 13 p. 4427 - 4445

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