Cinnamyl methyl 4-(3-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate | 119009-03-9

• 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: Cinnamyl methyl 4-(3-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: 3-O-methyl 5-O-(3-phenylprop-2-enyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 119009-03-9；119065-06-4；163923-05-5
• 化学式: C₂₅H₂₄N₂O₆
• 分子量: 448.475
• InChiKey: XTFPDGZNWTZCMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  肉桂醇 、 2,6-二甲基-5-甲氧羰基-4-(3-硝基苯基)-1,4-二氢吡啶-3-羧酸 在 乙酸酐 、 乙酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 Cinnamyl methyl 4-(3-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Antagonism of 4-substituted 1,4-dihydropyridine-3,5-dicarboxylates toward voltage-dependent L-type Ca2+ channels CaV1.3 and CaV1.2

  摘要：

  L-type Ca2+ channels in mammalian brain neurons have either a Ca(V)1.2 or Ca(V)1.3 pore-forming subunit. Recently, it was shown that Ca(V)1.3 Ca2+ channels underlie autonomous pacemaking in adult dopaminergic neurons in the substantia nigra pars compacta, and this reliance renders them sensitive to toxins used to create animal models of Parkinson's disease. Antagonism of these channels with the dihydropyridine antihypertensive drug isradipine diminishes the reliance on Ca2+ and the sensitivity of these neurons to toxins, pointing to a potential neuroprotective strategy. However, for neuroprotection without an antihypertensive side effect, selective Ca(V)1.3 channel antagonists are required. In an attempt to identify potent and selective antagonists of Ca(V)1.3 channels, 124 dihydropyridines (4-substituted-1,4-dihydropyridine3,5-dicarboxylic diesters) were synthesized. The antagonism of heterologously expressed Ca(V)1.2 and Ca(V)1.3 channels was then tested using electrophysiological approaches and the FLIPR Calcium 4 assay. Despite the large diversity in substitution on the dihydropyridine scaffold, the most Ca(V)1.3 selectivity was only about twofold. These results support a highly similar dihydropyridine binding site at both Ca(V)1.2 and Ca(V)1.3 channels and suggests that other classes of compounds need to be identified for Ca(V)1.3 selectivity. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.03.038

文献信息

• Antihypertensive 1,4-dihydropyridines having a conjugated ester
  申请人：Fujirebio Kabushiki Kaisha

  公开号：US04672068A1

  公开（公告）日：1987-06-09

  1,4-dihydropyridine derivatives represented by the following general formula, ##STR1## in which R.sup.3 is a combination of an unsaturated straight chain hydrocarbon group or derivative thereof connected by a single bond with an unsaturated hydrocarbon group or derivative thereof so that the unsaturated carbon atoms of the two groups are in conjugated relationship. These compounds have a hypotensive action the effective time of which is long, which makes the blood pressure descend slowly, and the toxicity of which is low.

  以下是一般式为##STR1##的1,4-二氢吡啶衍生物，其中R.sup.3是由一个不饱和直链烃基或其衍生物与一个不饱和烃基或其衍生物通过单键连接而组合而成，使得两个基团的不饱和碳原子处于共轭关系。这些化合物具有降压作用，其有效时间长，使得血压缓慢下降，毒性低。
• Antagonism of 4-substituted 1,4-dihydropyridine-3,5-dicarboxylates toward voltage-dependent L-type Ca2+ channels CaV1.3 and CaV1.2
  作者：Che-Chien Chang、Song Cao、Soosung Kang、Li Kai、Xinyong Tian、Prativa Pandey、Sara Fernandez Dunne、Chi-Hao Luan、D. James Surmeier、Richard B. Silverman

  DOI：10.1016/j.bmc.2010.03.038

  日期：2010.5

  L-type Ca2+ channels in mammalian brain neurons have either a Ca(V)1.2 or Ca(V)1.3 pore-forming subunit. Recently, it was shown that Ca(V)1.3 Ca2+ channels underlie autonomous pacemaking in adult dopaminergic neurons in the substantia nigra pars compacta, and this reliance renders them sensitive to toxins used to create animal models of Parkinson's disease. Antagonism of these channels with the dihydropyridine antihypertensive drug isradipine diminishes the reliance on Ca2+ and the sensitivity of these neurons to toxins, pointing to a potential neuroprotective strategy. However, for neuroprotection without an antihypertensive side effect, selective Ca(V)1.3 channel antagonists are required. In an attempt to identify potent and selective antagonists of Ca(V)1.3 channels, 124 dihydropyridines (4-substituted-1,4-dihydropyridine3,5-dicarboxylic diesters) were synthesized. The antagonism of heterologously expressed Ca(V)1.2 and Ca(V)1.3 channels was then tested using electrophysiological approaches and the FLIPR Calcium 4 assay. Despite the large diversity in substitution on the dihydropyridine scaffold, the most Ca(V)1.3 selectivity was only about twofold. These results support a highly similar dihydropyridine binding site at both Ca(V)1.2 and Ca(V)1.3 channels and suggests that other classes of compounds need to be identified for Ca(V)1.3 selectivity. (c) 2010 Elsevier Ltd. All rights reserved.