diethyl-2-acetoxymethyl-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate | 62760-94-5

• 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-acetoxymethyl-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: 2-acetoxymethyl-6-methyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester；diethyl 2-methyl-4-(3-nitrophenyl)-6-acetoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate；2-Acetoxymethyl-6-methyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester；diethyl 2-(acetyloxymethyl)-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 62760-94-5
• 化学式: C₂₁H₂₄N₂O₈
• 分子量: 432.43
• InChiKey: ZMPJLUJGNJLQPX-UHFFFAOYSA-N

物化性质

• 熔点：
  135-137 °C
• 沸点：
  553.2±50.0 °C(Predicted)
• 密度：
  1.261±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  137
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  diethyl-2-acetoxymethyl-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 在 chromium(VI) oxide 、 氢氧化钾 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 1.0h， 生成 ethyl-2-methyl-4-(3-nitrophenyl)-5-oxo-5,7-dihydrofuro<3,4-b>3-pyridinecarboxylate
  参考文献：
  名称：

  Meyer; Scherling; Karl, Arzneimittel-Forschung/Drug Research, 1983, vol. 33, # 11, p. 1528 - 1534

  摘要：

  DOI：
• 作为产物：
  描述：

  diethyl 2-methyl-4-(3-nitrophenyl)-6-formyl-1,4-dihydropyridine-3,5-dicarboxylate 在 吡啶 、 sodium tetrahydroborate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 diethyl-2-acetoxymethyl-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  尼伐地平的研究。I.在2-位含有新取代基的1，4-二氢吡啶的合成及其构效关系。

  摘要：

  描述了通过关键中间体2-甲酰基-1,4-二氢吡啶（X）合成在核的2-位含有新取代基的新的1,4-二氢吡啶衍生物。醛（X）的制备是通过Knoevenagel反应水解由芳基醛（V）和4,4-二烷氧基乙酰乙酸烷基酯（VI）得到的缩醛（IX）并按照3-氨基巴豆酸烷基酯（VIII）处理改进的Hantzsch方法。醛（X）的甲酰基具有足够的反应性，可以转化为各种官能团，例如羟甲基，氰基，取代的亚氨基甲基，氨基甲酰基，半氨基甲酸酯，取代的乙烯基，乙炔基等。在所有新化合物中，我们制备了2-羟甲基和2-氰基-1，在对血压正常的大鼠的低血压和戊巴比妥麻醉的狗的冠状动脉血流量增加的初步生物学评估中，发现4-二氢吡啶（IV和XXII）具有有效的活性。为了获得更有效的化合物，进行了2-羟基甲基-和2-氰基-1,4-二氢吡啶系列的优化研究。我们选择了异丙基2-氰基-3-甲氧基羰基-4-（3-硝基苯基）-6-甲基-1,

  DOI：

  10.1248/cpb.39.3189

文献信息

• 6-Acyloryalkyl-1,4-dihydropyridine derivatives and a method of effecting
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04145432A1

  公开（公告）日：1979-03-20

  This invention relates to 1,4-dihydropyridine derivatives. More particularly, it relates to new 1,4-dihydropyridine derivatives thereof which have vasodilating and anti-hypertensive activity, to processes for the preparation thereof, and to pharmaceutical composition comprising the same for therapeutical treatment in cardiovascular diseases and hypertension in human being.

  这项发明涉及1,4-二氢吡啶衍生物。更具体地，它涉及具有扩血管和降压活性的新1,4-二氢吡啶衍生物，以及其制备方法，以及包含相同的用于治疗人类心血管疾病和高血压的药物组合物。
• 1,4-Dihydropyridine derivatives, and pharmaceutical method of the same
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04284634A1

  公开（公告）日：1981-08-18

  1,4-dihydropyridine derivatives of the general formula ##STR1## having vasodilating and anti-hypertensive activity, processes for preparing same, and pharmaceutical compositions thereof for treating cardiovascular diseases.

  一般式为##STR1##的1,4-二氢吡啶衍生物具有扩血管和降压活性，制备方法以及用于治疗心血管疾病的药物组合物。
• 1,4-Dihydropyridine derivatives substituted in the 2 position, and their
  申请人：Bayer Aktiengesellschaft

  公开号：US04188395A1

  公开（公告）日：1980-02-12

  The present invention provides 1,4-dihydropyridine derivatives of the formula in which ##STR1## R represents hydrogen, alkyl, alkenyl, alkoxyalkyl, aryl or aralkyl, the alkyl and aryl groups being optionally substituted, A represents a straight-chain or branched alkylene radical, R.sup.1 represents (a) an optionally substituted alkylthio group or (b) a group of the formula O--CO-alkyl, O--CO-aryl or O--CO-aralkyl, the alkyl and aryl groups being optionally substituted or (c) a phthalimido radical which is optionally substituted in the benzene ring, Y and Z are identical or different and each represents a group of the formula COOR.sup.2 or COR.sup.2, wherein R.sup.2 represents alkyl, alkenyl, alkinyl, alkoxyalkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl or aralkyl, the alkyl and aryl radicals being optionally substituted, or Y and Z are identical or different and each represents a cyano radical or a radical of the formula S(O).sub.n --R.sup.3, wherein R.sup.3 represents alkyl, alkenyl, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, aryl or aralkyl, the alkyl and aryl radicals mentioned being optionally substituted, and n represents 0, 1 or 2, R.sup.4 represents hydrogen or alkyl, the alkyl radical being optionally substituted or interrupted by oxygen, or represents the radical A--R.sup.1, wherein A and R.sup.1 have the abovementioned meaning, and X represents an aryl radical, which optionally contains one to three identical or different substituents selected from phenyl, alkyl, alkenyl, alkinyl, alkoxy, alkinoxy, acyloxy, halogen, trifluoromethyl, trifluoromethoxy, hydroxyl, nitro, cyano, azido, amino, alkylamino, acylamino, carbalkoxy, carboxamido, sulphonamide and S(O).sub.n -alkyl (n=0 to 2), or represents a quinolyl, pyridyl, pyrimidyl, thienyl, furyl or pyrryl radical which is optionally substituted by alkyl, alkylamino, nitro or halogen, or represents an optionally substituted aralkyl, cycloalkyl, cycloalkenyl or styryl radical, and acid addition salts thereof. Also included in the invention are methods for the preparation of the 1,4-dihydropyridine derivatives of the invention, compositions containing said derivatives and methods for their use.

  本发明提供了公式中的1,4-二氢吡啶衍生物，其中##STR1## R代表氢、烷基、烯基、烷氧基烷基、芳基或芳基烷基，烷基和芳基基团可选择性地被取代，A代表直链或支链烷基基团，R.sup.1代表(a)可选择性取代的烷基硫基团或(b)公式O--CO-烷基、O--CO-芳基或O--CO-芳基烷基的基团，其中烷基和芳基基团可选择性地被取代，或(c)苯环中可选择性取代的邻苯二甲酰亚胺基团，Y和Z相同或不同，每个代表COOR.sup.2或COR.sup.2的基团，其中R.sup.2代表烷基、烯基、炔基、烷氧基烷基、羟基烷基、氨基烷基、烷基氨基烷基或芳基烷基，所述烷基和芳基基团可选择性被取代，或Y和Z相同或不同，每个代表氰基或公式S(O).sub.n --R.sup.3的基团，其中R.sup.3代表烷基、烯基、烷氧基烷基、氨基烷基、烷基氨基烷基、芳基或芳基烷基，所述所述烷基和芳基基团可选择性被取代，n代表0、1或2，R.sup.4代表氢或烷基，所述烷基基团可选择性被取代或被氧中断，或代表基团A--R.sup.1，其中A和R.sup.1具有上述所述的含义，X代表一个芳基基团，可选择性地含有一个至三个从苯基、烷基、烯基、炔基、烷氧基、烷氧基、酰氧基、卤素、三氟甲基、三氟甲氧基、羟基、硝基、氰基、叠氮基、氨基、烷基氨基、酰胺基、羧酰氧基、羧胺基、磺酰胺基和S(O).sub.n -烷基（n=0至2）中选择的相同或不同取代基，或代表一个可选择性取代的喹啉基、吡啶基、嘧啶基、噻吩基、呋喃基或吡咯基基团，该基团可选择性地被烷基、烷基氨基、硝基或卤素取代，或代表一个可选择性取代的芳基烷基、环烷基、环烯基或芳基烯基基团，以及其酸加盐。该发明还包括了制备所述衍生物的1,4-二氢吡啶的方法、含有所述衍生物的组合物以及其使用方法。
• 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.
• US4145432A
  申请人：——

  公开号：US4145432A

  公开（公告）日：1979-03-20