3-ethyl 5-(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate | 39562-75-9

• 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-ethyl 5-(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: ethyl methoxyethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate；2,6-dimethyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester-5-β-methoxyethyl ester；3-O-ethyl 5-O-(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 39562-75-9
• 化学式: C₂₀H₂₄N₂O₇
• 分子量: 404.42
• InChiKey: CKRWUIUJFBSMBV-UHFFFAOYSA-N

物化性质

• 熔点：
  83-85 °C
• 沸点：
  529.2±50.0 °C(Predicted)
• 密度：
  1.232±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3'-nitrobenzylideneacetoacetic acid β-methoxyethyl ester 、 3-氨基巴豆酸乙酯 以 甲醇 为溶剂， 以51%的产率得到3-ethyl 5-(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Pharmaceutical compositions containing unsymmetrical esters of

  摘要：

  含有不对称酯化的1,4-二氢吡啶-3,5-二羧酸的药物组合物作为活性成分，并使用方法。所述成分是在二氢吡啶核的4位被苯基取代的不对称1,4-二氢吡啶-3,5-二羧酸酯，该苯基含有至少一个硝基、氰基、叠氮基、烷基硫醚或烷基磺酰基取代基。这些组合物具有心血管活性，可用于促进冠状血管扩张，并且在治疗高血压方面具有用途。

  公开号：

  US03932645A1

文献信息

• 一种尼莫地平杂质Ⅳ对照品及其制备方法和应用
  申请人：湖南省药品检验研究院(湖南药用辅料检验检测中心)

  公开号：CN111875535A

  公开（公告）日：2020-11-03

  本发明公开了一种尼莫地平杂质Ⅳ对照品及其制备方法，所述方法为取双乙烯酮、乙醇、三乙胺，加入容器中加热，放冷，反应液水洗，弃去洗液，加入无水硫酸钠放置过夜，滤过得到滤液，在滤液中通入氨气至饱和，反应完成后加入间硝基苯甲醛、乙酰乙酸甲氧基乙酯、乙醇，加热回流，放冷，滤过，水浴挥干溶剂，得黄色黏稠液体，经重结晶得黄色针状结晶，即为尼莫地平杂质Ⅳ对照品，本发明还公开了尼莫地平杂质Ⅳ对照品在尼莫地平片一致性评价中的应用。本发明的制备方法可在一般分析实验室中制备得到杂质Ⅳ，无需特殊制备设备，操作简单，所得杂质对照品纯度可达98.4％，达到了对照品纯度要求，可用于该品种的一致性评价。
• Synthesis, Docking Simulation, Biological Evaluations and 3D-QSAR Study of 1,4-Dihydropyridines as Calcium Channel Blockers
  作者：Tarek Fathy El-Moselhy、Peter Ayoub Sidhom、Eman Ahmed Esmat、Nageh Ahmed El-Mahdy

  DOI：10.1248/cpb.c17-00186

  日期：——

  chelating effects of the C3 and C5 substituents. Bulky groups interfere with ring-to-ring hydrophobic interaction with tyrosine (Tyr)4311 and limit the efficiency of increasing the length of the hydrocarbon chain of esters at the 3- and 5-positions of the DHP ring as an approach to increasing the activity. The presence of a chelating substituent on the phenyl ring at the 4-position of the DHP ring ensures

  通过合成保留邻位或间位硝基苯环的两个系列硝苯地平类似物，已恢复了对靶L型电压依赖性钙通道的作用。对受体模型进行了先合成后的分子对接研究，然后进行分子比对，对47种化合物进行了预测，以预测活性最高的成员。IC50值表明某些化合物与硝苯地平相似或更具活性。在二氢吡啶（DHP）环的3位和5位上取代基团得到3k，它比硝苯地平更具活性。我们有效的三维定量构效关系（3D-QSAR）模型预示了亲脂性，蓬松度和C3和C5取代基的螯合效应的影响。庞大的基团会干扰酪氨酸（Tyr）4311的环对环疏水相互作用，并限制增加DHP环3和5位上的酯烃链长度的效率，以此作为提高活性的方法。DHP环的4位上苯环上的螯合取代基的存在可确保与受体的牢固结合，从而确保闭通道构象的稳定。3D-QSAR模型的验证表明其在预测属于同一化学类别的新化合物的活性方面的熟练程度。DHP环的4位上苯环上的螯合取代基的存在可确保与受体的牢固结
• Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60 cells
  作者：Jacquie L Harper、Carol S Camerini-Otero、An-Hu Li、Soon-Ai Kim、Kenneth A Jacobson、John W Daly

  DOI：10.1016/s0006-2952(02)01488-0

  日期：2003.2

  A series of 1,4-dihydropyridines (DHPs) were investigated as inhibitors of capacitative calcium influx through store-operated calcium (SOC) channels. Such channels activate after ATP-elicited release of inositol trisphosphate (IP3)-sensitive calcium stores in leukemia HL-60 cells. The most potent DHPs were those containing a 4-phenyl group with an electron-withdrawing substituent, such as m- or p-nitro- or in-trifluoromethyl (IC50 values: 3-6 muM). Benzyl esters, corresponding to the usual ethyl/methyl esters of the DHPs developed as L-type calcium channel blockers, retained potency at SOC channels, as did N-substituted DHPs. N-Methylation reduced by orders of magnitude the potency at L-type channels resulting in DHPs nearly equipotent at SOC and L-type channels. DHPs with N-ethyl, N-allyl, and N-propargyl groups also had similar potencies at SOC and L-type channels. Replacement of the usual 6-methyl group of DHPs with larger groups, such as cyclobutyl or phenyl, eliminated activity at the SOC channels; such DHPs instead elicited formation of inositol phosphates and release of IP3-sensitive calcium stores. Other DHPs also caused a release of calcium stores, but usually at significantly higher concentrations than those required for the inhibition of capacitative calcium influx. Certain DHPs appeared to cause an incomplete blockade of SOC channel-dependent elevations of calcium, suggesting the presence of more than one class of such channels in HL-60 cells. N-Methylnitrendipine (IC50 2.6 muM, MRS 1844) and N-propargylnifrendipine (IC50 1.7 muM, MRS 1845) represent possible lead compounds for the development of selective SOC channel inhibitors. Published by Elsevier Science Inc.
• US3932645A
  申请人：——

  公开号：US3932645A

  公开（公告）日：1976-01-13
• Pharmaceutical compositions containing unsymmetrical esters of
  申请人：Farbenfabriken Bayer AG

  公开号：US03932645A1

  公开（公告）日：1976-01-13

  Pharmaceutical compositions containing unsymmetrical esters of 1,4-dihydropyridine 3,5-dicarboxylic acids as the active ingredient and methods of using same. The said ingredients are unsymmetrical 1,4-dihydropyridine 3,5-dicarboxylates which are substituted at position-4 of the dihydropyridine nucleus by phenyl which contains at least one nitro, cyano, azido, alkylthio, or alkylsulphonyl substituent. The compositions have a cardiovascular activity which makes them useful for effecting coronary vascular dilation and, also, they have utility in the treatment of hypertension.

  含有不对称酯化的1,4-二氢吡啶-3,5-二羧酸的药物组合物作为活性成分，并使用方法。所述成分是在二氢吡啶核的4位被苯基取代的不对称1,4-二氢吡啶-3,5-二羧酸酯，该苯基含有至少一个硝基、氰基、叠氮基、烷基硫醚或烷基磺酰基取代基。这些组合物具有心血管活性，可用于促进冠状血管扩张，并且在治疗高血压方面具有用途。