1,4-dihydro-2,6-dimethyl-4-(3-chlorophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester | 73257-45-1

• 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: 1,4-dihydro-2,6-dimethyl-4-(3-chlorophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester
• 英文别名: (+/-)-dimethyl 4-(3-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate；dimethyl 4-(3-chlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate；dimethyl 4-(3-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate；dimethyl-4-(3-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 73257-45-1
• 化学式: C₁₇H₁₈ClNO₄
• mdl: MFCD01313941
• 分子量: 335.787
• InChiKey: AGKZWJBDPZPJDG-UHFFFAOYSA-N

物化性质

• 沸点：
  447.8±45.0 °C(Predicted)
• 密度：
  1.232±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,4-dihydro-2,6-dimethyl-4-(3-chlorophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester 在 N-溴代丁二酰亚胺(NBS) 、 硝酸 作用下， 以 氯仿 为溶剂， 反应 2.33h， 生成 1H,3H-Difuro(3,4-b:3',4'-e)pyridine-1,7(5H)-dione, 8-(3-chlorophenyl)-
  参考文献：
  名称：

  Synthesis and pharmacological activity of difuro-1,4-dihydropyridines

  摘要：

  DOI：

  10.1007/bf00764462
• 作为产物：
  描述：

  dimethyl 7-(3-chlorophenyl)-5,8a-dimethyl-2,3,7,8-tetrahydro-7H-oxazolo[3,2-a]pyridin-6,8-dicarboxylate 在 氢氧化钾 、 benzyl(triethyl)ammoniumpermanganate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 30.0h， 生成 1,4-dihydro-2,6-dimethyl-4-(3-chlorophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester
  参考文献：
  名称：

  Enantiospecific synthesis of dihydropyridines from chiral enamines

  摘要：

  A new asymmetric synthesis of dihydropyridines is described. This methodology is based on the use of chiral aminoalcohols to produce enamines, which were used in the synthesis of enantiopure 2-alkyl-2,3,8,8a-tetrahydro-7H-oxazolo[3,2-a]pyridines. The known stereochemistry of these compounds was exploited to obtain 1,4-dihydropyridines with controlled configuration at C-4. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0957-4166(96)00239-x

文献信息

• Synthesis of hantzsch 1,4-dihydropyridines under solvent-free condition using zn[(L)proline]₂as lewis acid catalyst
  作者：V. Sivamurugan、R. Suresh Kumar、M. Palanichamy、V. Murugesan

  DOI：10.1002/jhet.5570420534

  日期：2005.7

  The present short communication describes a Lewis acid (Zn[(L)proline]2) catalysed one pot synthesis of Hantzsch 1,4-dihydropyridine (DHP) derivatives under solvent-free condition by conventional heating and microwave irradiation. The Lewis acid catalyst Zn[(L)proline]2 used in this reaction afford moderate to good yield. The catalyst is reusable upto five cycles without appreciable loss of its catalytic

  本简短的交流描述了路易斯酸（Zn [（L）脯氨酸] 2）在无溶剂条件下通过常规加热和微波辐射催化一锅合成Hantzsch 1,4-二氢吡啶（DHP）衍生物。在该反应中使用的路易斯酸催化剂Zn [（L）脯氨酸] 2提供中等至良好的产率。该催化剂可重复使用多达五个循环，而不会明显丧失其催化活性。
• Oxidation of 4-aryl- and 4-alkyl-substituted 2,6-dimethyl-3,5-bis(alkoxycarbonyl)-1,4-dihydropyridines by human liver microsomes and immunochemical evidence for the involvement of a form of cytochrome P-450
  作者：Ronald H. Boecker、F. Peter Guengerich

  DOI：10.1021/jm00159a007

  日期：1986.9

  lost; these compounds also inactivated cytochrome P-450 and caused the loss of nifedipine oxidase activity after enzymatic oxidation. All of these reactions were extensively inhibited by an antibody raised to purified human liver nifedipine oxidase cytochrome P-450 (P-450NF), indicating a major role for this enzyme in the oxidation of these compounds. Oxidation of the 4-alkyl compounds led not only

  4-取代的2,6-二甲基-3,5-双（烷氧基羰基）-1,4-二氢吡啶很重要，因为它们作为钙通道阻滞剂。检查了人肝微粒体对14个4-芳基和四个4-烷基取代的衍生物的混合功能氧化。所有4-芳基化合物的酶促氧化的主要产物是含有4-芳基的吡啶衍生物。相反，4-烷基化合物形成吡啶衍生物，其中在4-位存在氢原子并且烷基丢失；这些化合物还使细胞色素P-450失活，并在酶促氧化后导致硝苯地平氧化酶活性丧失。所有这些反应均受到针对纯化的人肝硝苯地平氧化酶细胞色素P-450（P-450NF）的抗体的抑制，表明该酶在这些化合物的氧化中起主要作用。4-烷基化合物的氧化不仅导致P-450NF的损失，而且还导致细胞色素P-450同工酶催化其他反应（非那西丁O-去乙基化和己糖3'-羟基化）的催化活性降低。结果表明，P-450NF（或密切相关的酶形式）负责人肝微粒体中这些硝苯地平相关化合物的氧化，并且代谢高度依赖于4-取
• An efficient, metal-free, room temperature aromatization of Hantzsch-1,4-dihydropyridines with urea–hydrogen peroxide adduct, catalyzed by molecular iodine
  作者：Mirela Filipan-Litvić、Mladen Litvić、Vladimir Vinković

  DOI：10.1016/j.tet.2008.04.040

  日期：2008.6

  A mild, highly efficient and metal-free synthetic method for aromatization of 1,4-dihydropyridines employing urea–hydrogen peroxide adduct as oxidant catalyzed by 20 mol % of molecular iodine was developed. The reaction was carried out in ethyl acetate at room temperature and the products were isolated in high to excellent yields. A plausible free-radical mechanism is proposed based on results obtained

  开发了一种温和，高效，无金属的合成方法，该方法以20 mol％的分子碘为催化剂，使用脲-过氧化氢加合物作为氧化剂进行1,4-二氢吡啶的芳构化。该反应在室温下在乙酸乙酯中进行，并且以高至优异的产率分离出产物。基于在1，4-二氢吡啶环中具有烷基和芳基取代基的衍生物所获得的结果，提出了一种可能的自由基机理。
• Synthesis, Evaluation of Pharmacological Activity, and Molecular Docking of 1,4-Dihydropyridines as Calcium Antagonists
  作者：Moataz Ahmed Shaldam、Mervat Hamed El-Hamamsy、Dalia Osama Saleh、Tarek Fathy El-Moselhy

  DOI：10.1248/cpb.c15-00737

  日期：——

  approximately three-fold more active than nifedipine as a calcium antagonist. A docking study with the DHP receptor model was performed to interpret the differences in calcium antagonist activities. The molecular docking study demonstrated that the lipophilicity of the substituted phenyl group at the 4-position of the DHP ring is an important factor that could increase the activity of the calcium antagonist

  1,4-二氢吡啶（DHP）是一类重要的钙拮抗剂。它通过L型电压依赖性钙通道抑制细胞外Ca + 2的流入。合成了两个系列的硝苯地平类似物并评估为钙拮抗剂。硝苯地平的邻硝基苯基环被邻或间氯苯基取代基取代。IC50值表明，某些化合物的活性类似于硝苯地平或比硝苯地平更具活性。在DHP环的3和5位上用适当体积的基团（如乙酯）取代，得到3h，其活性比硝苯地平作为钙拮抗剂高3倍。进行了与DHP受体模型的对接研究，以解释钙拮抗剂活性的差异。分子对接研究表明，DHP环4位上的取代苯基的亲脂性是一个重要因素，考虑到空间因素，它可以增加钙拮抗剂的活性。庞大的基团干扰了与Tyr1460的环到环疏水相互作用，并限制了增加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一种方法。DHP环的4位上苯环上存在螯合取代基可确保与受体的牢固结合，从而确保闭通道构象的稳定。
• Magnetic Fe3O4 nanoparticles: Efficient and recoverable nanocatalyst for the synthesis of polyhydroquinolines and Hantzsch 1,4-dihydropyridines under solvent-free conditions
  作者：Masoud Nasr-Esfahani、S. Jafar Hoseini、Morteza Montazerozohori、Rasool Mehrabi、Hasan Nasrabadi

  DOI：10.1016/j.molcata.2013.11.010

  日期：2014.2

  A green approach for efficient and rapid synthesis of biologically active substituted Hantzsch 1,4-dihydropyridine and polyhydroquinoline derivatives using magnetic Fe3O4 nanoparticles (Fe3O4 MNPs) as a recyclable catalyst under solvent-free conditions was reported. The catalyst was characterized by FT-IR, XRD, and TEM analysis. Compared to the classical reactions, this method consistently has the

  报道了在无溶剂条件下使用磁性Fe 3 O 4纳米颗粒（Fe 3 O 4 MNPs）作为可循环利用催化剂高效，快速合成生物活性取代的Hantzsch 1,4-二氢吡啶和聚氢喹啉衍生物的绿色方法。通过FT-IR，XRD和TEM分析对催化剂进行了表征。与经典反应相比，该方法始终具有反应时间短，催化剂负载少，收率高，易于磁分离和催化剂可重复使用的优点。