3-ethyl5-methyl2-((2-(benzylamino)ethoxy)methyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-ethyl5-methyl2-((2-(benzylamino)ethoxy)methyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: 3-O-ethyl 5-O-methyl 2-[2-(benzylamino)ethoxymethyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
• 化学式: C₂₇H₃₁ClN₂O₅
• 分子量: 499.007
• InChiKey: YEAWYFJSTLVOOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  85.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  氨氯地平 、 苯甲腈 在 ammonia borane 、 C₁₆H₂₉Cl₂CoN₂P 作用下， 反应 13.0h， 以88%的产率得到3-ethyl5-methyl2-((2-(benzylamino)ethoxy)methyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  腈的轻度和选择性钴催化化学发散转移加氢

  摘要：

  在本文中，我们描述了腈的选择性钴催化化学发散转移氢化反应，以合成伯，仲和叔胺。溶剂效应对于选择性控制起着关键作用。该方法的普遍适用性以高化学选择性合成了70多种带有各种官能团的胺产物而得到了强调。此外，这种温和的系统实现了腈转移氢化的> 2000吨（周转数）。

  DOI：

  10.1002/anie.201608345

文献信息

• Dihydropyridines Potentiate ATP-Induced Currents Mediated by the Full-Length Human P2X5 Receptor
  作者：Ida C. Schiller、Kenneth A. Jacobson、Zhiwei Wen、Aparna Malisetty、Günther Schmalzing、Fritz Markwardt

  DOI：10.3390/molecules27061846

  日期：——

  The P2X5 receptor, an ATP-gated cation channel, is believed to be involved in tumor development, inflammatory bone loss and inflammasome activation after bacterial infection. Therefore, it is a worthwhile pharmacological target to treat the corresponding diseases, especially in minority populations that have a gene variant coding for functional homotrimeric P2X5 channels. Here, we investigated the effects of dihydropyridines on the human full-length P2X5 receptor (hP2X5FL) heterologously expressed in Xenopus oocytes using the two-microelectrode voltage clamp method. Agonist dependency, kinetics and permeation behavior, including Cl− permeability, were similar to hP2X5FL expressed in HEK293 or 1321N1 cells. Additionally, 1,4-dihydropyridines have been shown to interact with various other purinergic receptors, and we have examined them as potential hP2X5 modulators. Of seven commercially available and four newly synthesized dihydropyridines tested at hP2X5FL, only amlodipine exerted an inhibitory effect, but only at a high concentration of 300 µM. Isradipine and—even more—nimodipine stimulated ATP-induced currents in the low micromolar range. We conclude that common dihydropyridines or four new derivatives of amlodipine are not suitable as hP2X5 antagonists, but amlodipine might serve as a lead for future synthesis to increase its affinity. Furthermore, a side effect of nimodipine therapy could be a stimulatory effect on inflammatory processes.

  P2X5受体是一种ATP门控阳离子通道，被认为参与肿瘤发展、炎性骨质流失和细菌感染后的炎症小体激活。因此，它是治疗相应疾病的有价值的药理靶点，尤其是那些具有编码功能同三聚体P2X5通道的基因变异的少数族裔人群。在这里，我们使用两电极电压钳方法，在异种卵母中异种表达的人类全长P2X5受体（hP2X5FL）上研究了二氢吡啶对其的影响。激动剂依赖性、动力学和渗透行为，包括Cl−渗透性，与在HEK293或1321N1细胞中表达的hP2X5FL类似。此外，已经显示1,4-二氢吡啶与各种其他嘌呤受体相互作用，我们已将它们作为潜在的hP2X5调节剂进行了研究。在测试了七种商业上可获得的和四种新合成的二氢吡啶后，只有氨氯地平在高浓度300µM时产生了抑制作用。异丙地平和尼莫地平在低微摩尔范围内刺激了ATP诱导的电流。我们得出结论，常见的二氢吡啶或四个新的氨氯地平衍生物不适合作为hP2X5拮抗剂，但氨氯地平可能作为未来合成的引物来增加其亲和力。此外，尼莫地平治疗的一个副作用可能是对炎症过程的刺激作用。
• Mild and Selective Cobalt‐Catalyzed Chemodivergent Transfer Hydrogenation of Nitriles
  作者：Zhihui Shao、Shaomin Fu、Mufeng Wei、Shaolin Zhou、Qiang Liu

  DOI：10.1002/anie.201608345

  日期：2016.11.14

  Herein, we describe a selective cobalt‐catalyzed chemodivergent transfer hydrogenation of nitriles to synthesize primary, secondary, and tertiary amines. The solvent effect plays a key role for the selectivity control. The general applicability of this procedure was highlighted by the synthesis of more than 70 amine products bearing various functional groups in high chemoselectivity. Moreover, this

  在本文中，我们描述了腈的选择性钴催化化学发散转移氢化反应，以合成伯，仲和叔胺。溶剂效应对于选择性控制起着关键作用。该方法的普遍适用性以高化学选择性合成了70多种带有各种官能团的胺产物而得到了强调。此外，这种温和的系统实现了腈转移氢化的> 2000吨（周转数）。