2-(3,4-二甲氧基苯基)-5-{[2-(3,4-二甲氧基苯基)乙基]氨基}-2-异丙基戊腈盐酸盐(1:1) | 123931-31-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(3,4-二甲氧基苯基)-5-{[2-(3,4-二甲氧基苯基)乙基]氨基}-2-异丙基戊腈盐酸盐(1:1)
• 中文别名: 1-异氰酸基-2-[(4-异氰酸基苯基)甲基]苯1-异氰酸基-4-[(4-异氰酸基苯基)甲基]苯2-甲基噁丙环并噁丙环丙烷-1,2-二醇
• 英文名称: (-)-Norverapamil
• 英文别名: 5-((3,4-dimethoxyphenethyl)amino)-2-(3,4-dimethoxyphenyl)-2-isopropylpentanenitrile；(S)-desmethyl-verapamil；(S)-(-)-norverapamil；(S)-norverapamil；S-norverapamil；(2S)-2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylamino]-2-propan-2-ylpentanenitrile
• CAS: 123931-31-7
• 化学式: C₂₆H₃₆N₂O₄
• 分子量: 440.583
• InChiKey: UPKQNCPKPOLASS-SANMLTNESA-N

物化性质

• 熔点：
  131-133°C
• 沸点：
  586.1±50.0 °C(Predicted)
• 密度：
  1.063±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3,4-二甲氧基苯基)-5-{[2-(3,4-二甲氧基苯基)乙基]氨基}-2-异丙基戊腈盐酸盐(1:1) 、 [11C]methyl triflate 以 乙腈 为溶剂， 反应 0.08h， 以70.5%的产率得到(-)-3-(3,4-二甲氧基苯基)-6-[(5,6-二甲氧基苯乙基)甲基氨基]己烷-3-甲腈
  参考文献：
  名称：

  Fully automated high yield synthesis of (R)- and (S)-[11C]verapamil for measuring P-glycoprotein function with positron emission tomography

  摘要：

  消旋(±)维拉帕米是一种已被充分表征的P-糖蛋白(P-gp)底物。然而,两种对映体的体内药代动力学和药效学报道存在差异。在动物和人类中对两种对映体进行评价研究的准备过程中,本研究旨在优化和自动化合成(R)-和(S)-[11C]维拉帕米。(R)-和(S)-[11C]维拉帕米分别由(R)-和(S)-去甲维拉帕米通过无载体添加的[11C]甲基碘或[11C]甲基三氟化硫进行甲基化制备。研究了甲基化反应的不同条件:反应时间、温度、碱和溶剂,以及使用起始物质的盐酸盐或游离碱作为前体的化学形式。经过优化后,根据GMP指南,使用自制模块实现了合成的完全自动化。使用1.5 mg的(R)-或(S)-去甲维拉帕米的游离碱在0.5 ml的乙腈中于50°C下反应5分钟,并以[11C]甲基三氟化硫作为甲基化剂,获得了60-70%的最佳甲基化反应产率。在相同的反应条件下,但反应温度为100°C时,以[11C]甲基碘作为甲基化试剂的放射化学产率为40%。(R)-和(S)-[11C]维拉帕米的比活度均>20 GBq/μmol,且两种方法的放射化学纯度均>99%。总合成时间为45分钟。(R)-和(S)-[11C]维拉帕米的自动高产率合成为评估两种对映体作为P-gp功能的体内示踪剂提供了手段。版权所有 © 2002 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.632
• 作为产物：
  描述：

  去甲维拉帕米 生成 2-(3,4-二甲氧基苯基)-5-{[2-(3,4-二甲氧基苯基)乙基]氨基}-2-异丙基戊腈盐酸盐(1:1) 、 (alphaR)-alpha-[3-[[2-(3,4-二甲氧基苯基)乙基]氨基]丙基]-3,4-二甲氧基-alpha-(1-甲基乙基)-苯乙腈
  参考文献：
  名称：

  Maltooligosaccharides as Chiral Selectors for the Separation of Pharmaceuticals by Capillary Electrophoresis

  摘要：

  Complexation between the linear maltodextrin oligosaccharides and certain enantiomeric compounds of pharmaceutical interest in buffered solutions can lead to an analytically desirable chiral recognition. Different maltodextrins were assessed in their capacity to cause enantiomeric separations under various conditions of capillary electrophoresis. The mechanism of chiral recognition has been probed through electrophoretic mobility and selectivity measurements for different buffer solutions and organic solvent additives. A differential interaction of chiral solutes with the maltodextrin helical entities emerges as the basis of such enantioselectivity. This notion is further supported by H-1- and C-13-NMR experiments. Optimized separations of simendan, ibuprofen, warfarin, and ketoprofen enantiomers are demonstrated together with a chiral determination of ibuprofen in a blood serum sample at the therapeutic level.

  DOI：

  10.1021/ac00092a028

文献信息

• [EN] VERAPAMIL LIKE COMPOUNDS<br/>[FR] COMPOSÉS ANALOGUES AU VÉRAPAMIL
  申请人：STICHTING TECH WETENSCHAPP

  公开号：WO2014098593A9

  公开（公告）日：2014-10-23
• Luurtsema, G.; Windhorst, A. D.; Herscheid, J. D. M., Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S313 - S315
  作者：Luurtsema, G.、Windhorst, A. D.、Herscheid, J. D. M.、Molthoff, C. F. M.、Boellaard, R.、Smit, H.、Schinkel, A. H.、Lammertsma, A. A.、Franssen, E. J. F.

  DOI：——

  日期：——
• Fully automated high yield synthesis of (R)- and (S)-[11C]verapamil for measuring P-glycoprotein function with positron emission tomography
  作者：Gert Luurtsema、Albert D. Windhorst、Martien P.J. Mooijer、Jacobus D.M. Herscheid、Adriaan A. Lammertsma、Eric J.F. Franssen

  DOI：10.1002/jlcr.632

  日期：2002.12

  Racemic (±) verapamil is a well characterized substrate for P-glycoprotein (P-gp). However, the in vivo pharmacokinetics and pharmacodynamics of both enantiomers are reported to be different. In the preparation of evaluation studies of both enantiomers in animals and humans, the purpose of the present study was to optimize and automate the synthesis of (R)- and (S)-[11C]verapamil. (R)- and (S)-[11C]verapamil were prepared from (R)- and (S)-desmethyl-verapamil, respectively, by methylation with no-carrier added [11C]methyliodide or [11C]methyltriflate. Different conditions of the methylation reaction were studied: reaction time, temperature, base and solvent, and chemical form of the precursor using either the hydrochloric acid salt or the free base of the starting material. After optimization, the synthesis was fully automated using home-made modules and performed according to GMP guidelines. Optimal yields of 60–70% for the methylation reaction were obtained using 1.5 mg of the free base of (R)- or (S)-desmethyl-verapamil in 0.5 ml of acetonitrile at 50°C for 5 min with [11C]methyltriflate as methylating agent. Under the same reaction conditions, but with a reaction temperature of 100°C, the radiochemical yield starting with [11C]methyliodide as methylation reagent was 40%. The specific activity of (R)- and (S)-[11C]verapamil was >20 GBq/μmol and the radiochemical purity was >99% for both methods. The total synthesis time was 45 min. The automated high yield synthesis of (R)- and (S)-[11C]verapamil provides the means for evaluating both enantiomers as in vivo tracers of P-gp function. Copyright © 2002 John Wiley & Sons, Ltd.

  消旋(±)维拉帕米是一种已被充分表征的P-糖蛋白(P-gp)底物。然而,两种对映体的体内药代动力学和药效学报道存在差异。在动物和人类中对两种对映体进行评价研究的准备过程中,本研究旨在优化和自动化合成(R)-和(S)-[11C]维拉帕米。(R)-和(S)-[11C]维拉帕米分别由(R)-和(S)-去甲维拉帕米通过无载体添加的[11C]甲基碘或[11C]甲基三氟化硫进行甲基化制备。研究了甲基化反应的不同条件:反应时间、温度、碱和溶剂,以及使用起始物质的盐酸盐或游离碱作为前体的化学形式。经过优化后,根据GMP指南,使用自制模块实现了合成的完全自动化。使用1.5 mg的(R)-或(S)-去甲维拉帕米的游离碱在0.5 ml的乙腈中于50°C下反应5分钟,并以[11C]甲基三氟化硫作为甲基化剂,获得了60-70%的最佳甲基化反应产率。在相同的反应条件下,但反应温度为100°C时,以[11C]甲基碘作为甲基化试剂的放射化学产率为40%。(R)-和(S)-[11C]维拉帕米的比活度均>20 GBq/μmol,且两种方法的放射化学纯度均>99%。总合成时间为45分钟。(R)-和(S)-[11C]维拉帕米的自动高产率合成为评估两种对映体作为P-gp功能的体内示踪剂提供了手段。版权所有 © 2002 John Wiley & Sons, Ltd.
• Maltooligosaccharides as Chiral Selectors for the Separation of Pharmaceuticals by Capillary Electrophoresis
  作者：Helena. Soini、Morgan. Stefansson、Marja-Liisa. Riekkola、Milos V. Novotny

  DOI：10.1021/ac00092a028

  日期：1994.10.15

  Complexation between the linear maltodextrin oligosaccharides and certain enantiomeric compounds of pharmaceutical interest in buffered solutions can lead to an analytically desirable chiral recognition. Different maltodextrins were assessed in their capacity to cause enantiomeric separations under various conditions of capillary electrophoresis. The mechanism of chiral recognition has been probed through electrophoretic mobility and selectivity measurements for different buffer solutions and organic solvent additives. A differential interaction of chiral solutes with the maltodextrin helical entities emerges as the basis of such enantioselectivity. This notion is further supported by H-1- and C-13-NMR experiments. Optimized separations of simendan, ibuprofen, warfarin, and ketoprofen enantiomers are demonstrated together with a chiral determination of ibuprofen in a blood serum sample at the therapeutic level.