diethyl 2,4-dimethyl-6-phenylpyridine-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: diethyl 2,4-dimethyl-6-phenylpyridine-3,5-dicarboxylate
• 英文别名: diethyl 2-phenyl-4,6-dimethylpyridine-3,5-dicarboxylate
• 化学式: C₁₉H₂₁NO₄
• 分子量: 327.38
• InChiKey: FFBUJODBLJEOGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  65.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氨基巴豆酸乙酯 在 四氯苯醌 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 4.0h， 生成 diethyl 2,4-dimethyl-6-phenylpyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Interaction of 1,4-Dihydropyridine and Pyridine Derivatives with Adenosine Receptors:  Selectivity for A₃ Receptors

  摘要：

  1,4-Dihydropyridine and pyridine derivatives bound to three subtypes of adenosine receptors in the micromolar range. Affinity was determined in radioligand binding assays at rat brain A(1) and A(2A) receptors using [H-3]-(R)-PIA [[H-3]-(R)-N-6-(phenylisopropyl)adenosine] and [H-3]CGS 21680 [[H-3]-2-[[4-(2-carboxyethyl)phenyl]ethylamino]-5'-(N-ethylcarbamoyl)adenosine], respectively. Affinity was determined at cloned human and rat A(3) receptors using [I-125]AB-MECA [N-6-(4-amino-3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine]. Structure-activity analysis at adenosine receptors indicated that sterically bulky groups at the 4-, 5-, and 6-positions are tolerated. (R,S)-Nicardipine, 12, displayed K-i values of 19.6 and 63.8 mu M at rat A(1) and A(2A) receptors, respectively, and 3.25 mu M at human A(3) receptors. Similarly, (R)-niguldipine, 14, displayed K-i values of 41.3 and 1.90 mu M at A(1) and A(3) receptors, respectively, and was inactive at A(2A) receptors. A preference for the R- vs the S-enantiomer was observed for several dihydropyridines at adenosine receptors, in contrast with the selectivity at L-type Ca2+ channels. A 4-trans-beta-styryl derivative, 24, with a K-i value of 0.670 mu M at A(3) receptors, was 24-fold selective vs A(1) receptors (K-i = 16.1 mu M) and 74-fold vs A(2A) receptors (K-i = 49.3 mu M). The affinity of 24 at L-type Ca2+ channels, measured in rat brain membranes using [H-3]isradipine, indicated a K-i value of 0.694 mu M, and the compound is thus nonselective between A(3) receptors and L-type Ca2+ channels. Inclusion of a 6-phenyl group enhanced A(3) receptor selectivity: Compound 28 (MRS1097; 3,5-diethyl 2-methyl-6-phenyl-4-(trans-2-phenylvinyl)-1,4(R,S)-dihydro-pyridine-3,5-dicarboxylate) was 55-fold selective vs A(1) receptors, 44-fold selective vs A(2A) receptors, and over 1000-fold selective vs L-type Ca2+ channels. In addition, compound 28 attenuated the A(3) agonist-elicited inhibitory effect on adenylylcyclase. Furthermore, whereas nicardipine, 12, displaced radioligand from the Na+-independent adenosine transporter with an apparent affinity of 5.36 +/- 1.51 mu M, compound 28 displaced less than 10% of total binding at a concentration of 100 mu M. Pyridine derivatives, when bearing a 4-alkyl but not a 4-phenyl group, maintained affinity for adenosine receptors. These findings indicate that the dihydropyridines may provide leads for the development of novel, selective A(3) adenosine antagonists.

  DOI：

  10.1021/jm9600205

文献信息

• Ruthenium bipyridyl tethered porous organosilica: a versatile, durable and reusable heterogeneous photocatalyst
  作者：Avijit Jana、John Mondal、Parijat Borah、Sujan Mondal、Asim Bhaumik、Yanli Zhao

  DOI：10.1039/c5cc03067f

  日期：——

  Ruthenium bipyridyl tethered mesoporous organosilica (Ru-POS) was developed as a versatile heterogeneous photoredox catalyst in several organic transformations.

  钌联吡啶锚定的介孔有机硅（Ru-POS）被开发为多功能的杂化光催化剂，在几种有机转化中发挥作用。
• The Multicomponent Hantzsch Reaction: Comprehensive Mass Spectrometry Monitoring Using Charge-Tagged Reagents
  作者：Vanessa G. Santos、Marla N. Godoi、Thaís Regiani、Fernando H. S. Gama、Mirela B. Coelho、Rodrigo O. M. A. de Souza、Marcos N. Eberlin、Simon J. Garden

  DOI：10.1002/chem.201303065

  日期：2014.9.26

  for the ESI‐MS monitoring of reaction solutions involving the alternate use of permanently charge‐tagged reagents has been used for comprehensive mass spectrometry monitoring of the multicomponent Hantzsch 1,4‐dihydropyridine reaction. By placing a charge tag on either, or both, of the two key reactants, ion suppression effects for ESI were eliminated or minimized, and comprehensive detection of charge‐tagged

  一种用于ESI-MS监测反应溶液的新策略，涉及交替使用带有永久电荷标签的试剂，已用于多组分Hantzsch 1,4-二氢吡啶反应的全面质谱监测。通过在两个关键反应物之一或两者上加一个电荷标签，消除或最小化了对ESI的离子抑制作用，从而实现了对带电荷中间体的全面检测。该策略可以捕获和表征1,4-二氢吡啶形成机理中的重要中间体。
• Trinuclear cis-dioxidomolybdenum(VI) complexes of compartmental C symmetric ligands: Synthesis, characterization, DFT study and catalytic application for hydropyridines (Hps) via the Hantzsch reaction
  作者：Mannar R. Maurya、Reshu Tomar、Puneet Gupta、Fernando Avecilla

  DOI：10.1016/j.poly.2020.114617

  日期：2020.8

  electrochemical study, elemental analysis, thermogravimetric study and single crystal X-ray diffraction of the ligand III and complexes 1 and 5. In the presence of H2O2 as an oxidant, these complexes show excellent catalytic potential towards the one-pot three-components [ethyl acetoacetate, benzaldehyde (or its derivatives) and ammonium acetate] dynamic covalent assembly in the Hantzsch reaction. Under solvent

  摘要[TriMo（H2ONO）供体配体[H6L1-7（I–VII）]是由[MoVIO2（MeOH）} 3L1-7]（1–7）型三核顺式-二氧化钼（VI）络合物合成的。苯-1,3,5-三甲酰肼（bthz）和相应的水杨醛（sal）。所有配体和配合物均通过多种技术进行表征，例如FT-IR，紫外可见，NMR（1H和13C）光谱，电化学研究，元素分析，热重分析和配体III和X的单晶X射线衍射。配合物1和5。在存在H2O2作为氧化剂的情况下，这些配合物在Hantzsch反应中显示出对一锅三组分（乙酰乙酸乙酯，苯甲醛（或其衍生物）和乙酸铵）动态共价组装的出色催化潜力。在无溶剂条件下，在1小时内已实现高达98％的转化率以及对2,6-二甲基-4-苯基-1,4-二氢吡啶-3,5-二羧酸二乙酯（1,4-DHP）的100％选择性。尽管溶剂不能改善转化率，但它们确实会影响产物的选择性。随着时间的流逝，二氢吡啶向2
• A revisit to the Hantzsch reaction: Unexpected products beyond 1,4-dihydropyridines
  作者：Li Shen、Song Cao、Jingjing Wu、Jian Zhang、Hui Li、Nianjin Liu、Xuhong Qian

  DOI：10.1039/b906358g

  日期：——

  A novel green and efficient one-pot three-component synthesis of 2-aryl-pyridines in good to excellent yields has been reported. The methodology initially involved the formation of 1,2-dihydropyridine intermediates via reaction of a variety of aromatic aldehydes with ethyl (methyl) acetoacetate and ammonium acetate, which were the same starting materials as the Hantzsch reaction, under solvent-, catalyst- and heat-free (at room temperature) conditions, followed by air oxidation for 72 hours. In this paper, we also systematically reinvestigated the classic Hantzsch reaction under different reaction conditions, analyzed the main products as well as byproducts, corrected some mistakes in the literature and elucidated the reaction mechanism.

  据报道，一种新型绿色高效的单锅三组分合成 2-芳基吡啶的方法获得了良好甚至极佳的产率。该方法最初是在溶剂、催化剂和无热（室温）条件下，通过多种芳香醛与乙酰乙酸乙酯（甲基）和乙酸铵（与 Hantzsch 反应的起始原料相同）反应生成 1,2-二氢吡啶中间体，然后在空气中氧化 72 小时。在本文中，我们还系统地重新研究了不同反应条件下的经典 Hantzsch 反应，分析了主要产物和副产物，纠正了文献中的一些错误，并阐明了反应机理。
• Interaction of 1,4-Dihydropyridine and Pyridine Derivatives with Adenosine Receptors:  Selectivity for A₃ Receptors
  作者：A. Michiel van Rhee、Ji-long Jiang、Neli Melman、Mark E. Olah、Gary L. Stiles、Kenneth A. Jacobson

  DOI：10.1021/jm9600205

  日期：1996.1.1

  1,4-Dihydropyridine and pyridine derivatives bound to three subtypes of adenosine receptors in the micromolar range. Affinity was determined in radioligand binding assays at rat brain A(1) and A(2A) receptors using [H-3]-(R)-PIA [[H-3]-(R)-N-6-(phenylisopropyl)adenosine] and [H-3]CGS 21680 [[H-3]-2-[[4-(2-carboxyethyl)phenyl]ethylamino]-5'-(N-ethylcarbamoyl)adenosine], respectively. Affinity was determined at cloned human and rat A(3) receptors using [I-125]AB-MECA [N-6-(4-amino-3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine]. Structure-activity analysis at adenosine receptors indicated that sterically bulky groups at the 4-, 5-, and 6-positions are tolerated. (R,S)-Nicardipine, 12, displayed K-i values of 19.6 and 63.8 mu M at rat A(1) and A(2A) receptors, respectively, and 3.25 mu M at human A(3) receptors. Similarly, (R)-niguldipine, 14, displayed K-i values of 41.3 and 1.90 mu M at A(1) and A(3) receptors, respectively, and was inactive at A(2A) receptors. A preference for the R- vs the S-enantiomer was observed for several dihydropyridines at adenosine receptors, in contrast with the selectivity at L-type Ca2+ channels. A 4-trans-beta-styryl derivative, 24, with a K-i value of 0.670 mu M at A(3) receptors, was 24-fold selective vs A(1) receptors (K-i = 16.1 mu M) and 74-fold vs A(2A) receptors (K-i = 49.3 mu M). The affinity of 24 at L-type Ca2+ channels, measured in rat brain membranes using [H-3]isradipine, indicated a K-i value of 0.694 mu M, and the compound is thus nonselective between A(3) receptors and L-type Ca2+ channels. Inclusion of a 6-phenyl group enhanced A(3) receptor selectivity: Compound 28 (MRS1097; 3,5-diethyl 2-methyl-6-phenyl-4-(trans-2-phenylvinyl)-1,4(R,S)-dihydro-pyridine-3,5-dicarboxylate) was 55-fold selective vs A(1) receptors, 44-fold selective vs A(2A) receptors, and over 1000-fold selective vs L-type Ca2+ channels. In addition, compound 28 attenuated the A(3) agonist-elicited inhibitory effect on adenylylcyclase. Furthermore, whereas nicardipine, 12, displaced radioligand from the Na+-independent adenosine transporter with an apparent affinity of 5.36 +/- 1.51 mu M, compound 28 displaced less than 10% of total binding at a concentration of 100 mu M. Pyridine derivatives, when bearing a 4-alkyl but not a 4-phenyl group, maintained affinity for adenosine receptors. These findings indicate that the dihydropyridines may provide leads for the development of novel, selective A(3) adenosine antagonists.