2-cyanoethyl (R)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-3-pyridinecarboxylate | 143167-32-2

• 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: 2-cyanoethyl (R)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-3-pyridinecarboxylate
• 英文别名: (-)-2-cyanoethyl methyl (R)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate；RV44U7TH5A；5-O-(2-cyanoethyl) 3-O-methyl (4R)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 143167-32-2
• 化学式: C₁₉H₁₉N₃O₆
• 分子量: 385.376
• InChiKey: PVYKGJCGTZQNJL-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 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：
  134
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-cyanoethyl (R)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-3-pyridinecarboxylate 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 生成 (S)-(+)-1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二甲酸单甲酯
  参考文献：
  名称：

  蛋白酶催化的光学活性14-二氢吡啶的对映选择性合成

  摘要：

  开发了1,4-二氢吡啶-3,5-二羧基二酯的第一个对映选择性蛋白酶催化的水解物。所获得的单酯具有高的光学纯度，并且是有用的手性结构单元，其可以容易地产生光学活性的Cablockers。

  DOI：

  10.1016/s0040-4039(00)79178-7
• 作为产物：
  描述：

  bis(2-cyanoethyl) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-pyridine 3,5-dicarboxylate 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 72.0h， 生成 2-cyanoethyl (R)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-3-pyridinecarboxylate
  参考文献：
  名称：

  蛋白酶催化的光学活性14-二氢吡啶的对映选择性合成

  摘要：

  开发了1,4-二氢吡啶-3,5-二羧基二酯的第一个对映选择性蛋白酶催化的水解物。所获得的单酯具有高的光学纯度，并且是有用的手性结构单元，其可以容易地产生光学活性的Cablockers。

  DOI：

  10.1016/s0040-4039(00)79178-7

文献信息

• 1,4-dihydropyridine derivatives
  申请人：Fujirebio Inc.

  公开号：US05367081A1

  公开（公告）日：1994-11-22

  1,4-dihydropyridine derivatives and optically active 1,4-dihydropyridine derivatives with the following formula, having vasodilating activity based on calcium antagonism, and PAF antaognism, and methods of producing the same are disclosed: ##STR1## wherein (*) indicates a chiral center in the case of the optically active 1,4-dihydropyridine derivatives.

  1,4-二氢吡啶衍生物和具有以下结构式的光学活性1,4-二氢吡啶衍生物，基于钙拮抗作用具有扩血管活性，以及PAF拮抗作用，以及生产这些物质的方法已被披露：##STR1## 其中(*)表示在光学活性1,4-二氢吡啶衍生物中的手性中心。
• 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.
• Carbamoylmethyl group as an activated group in protease- and base-catalyzed transesterification of 1,4-dihydropyridines: A novel asymmetric synthesis of valnidipine
  作者：Yoshihiko Hirose、Kinya Kariya、Ikuharu Sasaki、Yoshiaki Kurono、Kazuo Achiwa

  DOI：10.1016/s0040-4039(00)73813-5

  日期：1993.9

  The first protease-catalyzed enantioselective transesterification of 1,4-dihydropyridine-3,5-dicarboxylates in an aqueous solution was developed with high optical purity. Carbamoylmethyl ester group was enantioselectively transesterificated with (S)-N-benzyl-3-pyrroridinol by the protease and successive base-catalyzed transesterification proceeded smoothly to give the chiral drug, valnidipine, in a good yield.