diethyl 2,6-dimethyl-4-(3-aminophenyl)-1,4-dihydropyridine-3,5-dicarboxylate | 21889-32-7

• 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: diethyl 2,6-dimethyl-4-(3-aminophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: 4-(3-amino-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester；4-(3-Amino-phenyl)-2,6-dimethyl-1,4-dihydro-pyridin-3,5-dicarbonsaeure-diaethylester；2,6-dimethyl-4-(3'-aminophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester；diethyl 4-(3-aminophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 21889-32-7
• 化学式: C₁₉H₂₄N₂O₄
• 分子量: 344.411
• InChiKey: KSQJQDAPMJCFDK-UHFFFAOYSA-N

物化性质

• 熔点：
  151-152 °C(Solvent: Ethanol)
• 沸点：
  500.0±45.0 °C(predicted)
• 密度：
  1.164±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl 2,6-dimethyl-4-(3-aminophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 在 potassium carbonate 、 苯 作用下， 生成 N,N-diethyl-3-(3,5-bis-ethoxycarbonyl-2,6-dimethyl-1,4-dihydro-[4]pyridyl)-N-methyl-anilinium; iodide
  参考文献：
  名称：

  Hantzsch's Pyridine Synthesis

  摘要：

  DOI：

  10.1021/ja01180a037
• 作为产物：
  描述：

  3-氨基巴豆酸乙酯 在 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 diethyl 2,6-dimethyl-4-(3-aminophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60 cells

  摘要：

  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.

  DOI：

  10.1016/s0006-2952(02)01488-0

文献信息

• 1,4-Dihydropyridines
  申请人：Bayer Aktiengesellschaft

  公开号：US03959296A1

  公开（公告）日：1976-05-25

  Derivatives of 4-substituted phenyl 1,4-dihydropyridine 3,5-dicarboxylic acids substituted by lower alkyl groups in the 2- and 6-positions, are cardiovascular agents. The compounds, of which 2,6-dimethyl-4-[2-(diethylaminoethoxy)-phenyl]-1,4-dihydropyridine-3,5-dic arboxylic acid 3,5-diethyl ester is a typical example, can be prepared through condensation of a .beta.-dicarbonyl compound with an amine and an aldehyde, of an ylidene-.beta.-ketocarboxylic acid ester, with a .beta.-ketocarbonyl compound and an amine, of an aldehyde, an enamine and a .beta.-ketocarbonyl compound, or through elaboration of the substituent on the phenyl group.

  4-取代苯基1,4-二氢吡啶-3,5-二羧酸的衍生物，其在2-和6-位被较低的烷基取代，是心血管药物。这些化合物，其中2,6-二甲基-4-[2-(二乙氨基乙氧基)-苯基]-1,4-二氢吡啶-3,5-二羧酸3,5-二乙酯是一个典型的例子，可以通过将β-二羰基化合物与胺和醛、与一个叶基-β-酮羧酸酯、与一个β-酮羰基化合物和一个胺、与一个醛、一个烯胺和一个β-酮羰基化合物进行缩合，或通过对苯基上的取代基进行详细处理来制备。
• Synthesis and Pharmacological Evaluation of Novel Homocamptothecin-Dihydropyridine Derivative Conjugates as Potent Topoisomerase I Inhibitors
  作者：Ling-Jian Zhu、Chun-Lin Zhuang、Ning Lei、Chun-Quan Sheng、Wei Guo、Zhen-Yuan Miao、Wen-Feng Liu、Jian-Zhong Yao、Wan-Nian Zhang

  DOI：10.1071/ch11091

  日期：——

  agents targeting DNA topoisomerase I. The expanded seven-membered lactone E-ring that characterizes hCPT enhances the plasma stability of the drug and reinforces the inhibition of topoisomerase I (Topo I) compared with conventional six-membered CPT. In an attempt to improve the antitumour activity of hCP, a series of novel hCPT derivatives conjugating with dihydropyridine derivates were designed and synthesized

  同型喜树碱（hCPT）代表了针对DNA拓扑异构酶I的新一代抗肿瘤药物。与传统的六种抗肿瘤药物相比，表征hCPT的扩展的七元内酯E环增强了药物的血浆稳定性并增强了对拓扑异构酶I（Topo I）的抑制作用。成员的CPT。为了改善hCP的抗肿瘤活性，基于将7-甲酰基高喜树碱与不同的二氢吡啶衍生物偶联的合成路线，设计并合成了与二氢吡啶衍生物缀合的一系列新颖的hCPT衍生物。大多数合成的化合物对肿瘤细胞系A549，MDA-MB-435和HCT116表现出良好的细胞毒活性。此外，这类化合物显示出与CPT相当或更高的Topo I抑制活性。
• Synthesis and vasodilator activity of new 1,4-dihyropyridines bearing sulfonylurea, urea and thiourea moieties
  作者：Mohamed Zakaria Stiti、Mebrouk Belghobsi、Tahir Habila、Eric Goffin、Pascal de Tullio、Bernard Pirotte、Gilles Faury、Smail Khelili

  DOI：10.1007/s11696-019-00925-4

  日期：2020.3

  electro-withdrawing substituents) gave very active compounds. The inactiveness of sulfonylurea derivatives could be explained by a partial ionization at physiological pH because of their weak acid character. Finally, it would be very suitable to synthesize N-methylated analogs of sulfonylurea derivatives, and more urea and thiourea derivatives bearing aliphatic R groups, and to test them on the same pharmacological

  摘要合成了一些带有磺酰脲，尿素和硫脲部分的新的1,4-二氢吡啶，并进行了药理学评估（与硝苯地平和重氮相比）。对大鼠主动脉环上目标化合物的研究表明，除无活性的磺酰脲类衍生物（EC 50  > 100μM）外，尿素和硫脲衍生物均表现出中等至强的血管扩张活性，EC 50值在1.2至40μM之间变化。17倍的二氮嗪多种活性（但比硝苯地平活性较低），最活跃的化合物（发现1.2±0.2μM）是一种电压门控钙通道阻滞剂，参考化合物硝苯地平就是这种情况。结果还表明，脂族或芳族R基团（后者带有供电子或吸电取代基）产生非常活泼的化合物。磺酰脲衍生物的无活性可以通过生理pH值的部分电离来解释，因为它们的弱酸特性。最后，非常适合合成N-磺酰脲衍生物的甲基化类似物，以及更多带有脂肪族R基团的脲和硫脲衍生物，并在相同的药理模型上进行测试。因此，本文所述的1，4-二氢吡啶系列显示出开发新的血管扩张剂的良好潜力，以寻找用于治疗某些心血管疾病的新疗法。
• Synthesis and pharmacological activity of 4-aryl-1,4-dihydropyridines with fluorinated nitrogen-containing substituents in the benzene ring
  作者：L. M. Yagupol'skii、S. S. Shavaran、B. M. Klebanov、A. N. Rechitskii、I. I. Maletina

  DOI：10.1007/bf02218711

  日期：1994.11
• US3959296A
  申请人：——

  公开号：US3959296A

  公开（公告）日：1976-05-25