(E,Z)-2-[2-(difluoromethoxy)benzylidene]propoxyethyl acetoacetate | 400884-02-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E,Z)-2-[2-(difluoromethoxy)benzylidene]propoxyethyl acetoacetate
• 英文别名: 2-propoxyethyl 2-[[2-(difluoromethoxy)phenyl]methylidene]-3-oxobutanoate
• CAS: 400884-02-8
• 化学式: C₁₇H₂₀F₂O₅
• 分子量: 342.34
• InChiKey: ZHBPMZHSZMGPCL-UHFFFAOYSA-N

物化性质

• 沸点：
  425.3±40.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.23
• 重原子数：
  24.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  61.83
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (E,Z)-2-[2-(difluoromethoxy)benzylidene]propoxyethyl acetoacetate 在 氢氧化钾 、 磷脂酶B 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 22.5h， 生成 (4S)-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-5-[(2-propoxyethoxy)carbonyl]-1,4-dihydro-3-pyridinecarboxylic acid
  参考文献：
  名称：

  Effect of Acyl Chain Length and Branching on the Enantioselectivity of Candida rugosa Lipase in the Kinetic Resolution of 4-(2-Difluoromethoxyphenyl)-Substituted 1,4-Dihydropyridine 3,5-Diesters

  摘要：

  Since 2,6-dimethyl-4-aryl-1,4-dihydropyridine 3,5-diesters themselves are not hydrolyzed by commercially available hydrolases, derivatives with spacers containing a hydrolyzable group were prepared. Seven acyloxymethyl esters of 5-methyl- and 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate were synthesized and subjected to Candida rugosa lipase (CRL) catalyzed hydrolysis in wet diisopropyl ether. A methyl ester at the 5-position and a long or branched acyl chain at C3 gave the highest enantiomeric ratio (E values). The most stereoselective reaction (E = 21) was obtained with 3-[(isobutyryloxy)methyl] 5-methyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and this compound was used to prepare both enantiomers of 3-methyl 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate. The absolute configuration of the enzymatically produced carboxylic acid was established to be 4R by X-ray crystallographic analysis of its 1-(R)-phenylethyl amide.

  DOI：

  10.1021/jo0104025
• 作为产物：
  描述：

  acetoacetic acid β-propoxyethyl ester 、 (二氟甲氧基)苯甲醛 在 哌啶 、 溶剂黄146 作用下， 以 异丙醇 为溶剂， 反应 5.0h， 生成 (E,Z)-2-[2-(difluoromethoxy)benzylidene]propoxyethyl acetoacetate
  参考文献：
  名称：

  Effect of Acyl Chain Length and Branching on the Enantioselectivity of Candida rugosa Lipase in the Kinetic Resolution of 4-(2-Difluoromethoxyphenyl)-Substituted 1,4-Dihydropyridine 3,5-Diesters

  摘要：

  Since 2,6-dimethyl-4-aryl-1,4-dihydropyridine 3,5-diesters themselves are not hydrolyzed by commercially available hydrolases, derivatives with spacers containing a hydrolyzable group were prepared. Seven acyloxymethyl esters of 5-methyl- and 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate were synthesized and subjected to Candida rugosa lipase (CRL) catalyzed hydrolysis in wet diisopropyl ether. A methyl ester at the 5-position and a long or branched acyl chain at C3 gave the highest enantiomeric ratio (E values). The most stereoselective reaction (E = 21) was obtained with 3-[(isobutyryloxy)methyl] 5-methyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and this compound was used to prepare both enantiomers of 3-methyl 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate. The absolute configuration of the enzymatically produced carboxylic acid was established to be 4R by X-ray crystallographic analysis of its 1-(R)-phenylethyl amide.

  DOI：

  10.1021/jo0104025

文献信息

• Calcium Level Controlling Activities of Novel Derivatives of Amlodipine,Riodipine and Cerebrocrast
  作者：R. Vilskersts、B. Vigante、Z. Neidere、A. Krauze、I. Domracheva、L. Bekere、I. Shestakova、G. Duburs、M. Dambrova

  DOI：10.2174/157018012799129909

  日期：2012.3.1

  A novel series of asymmetric 4-aryl-1,4-dihydropyridine (1,4-DHP) 3,5-diester derivatives and their symmetric analogues comprised of functional moieties of amlodipine, riodipine and cerebrocrast have been synthesized. The calcium channel blocking activity was evaluated in an isolated rat aortic ring model. The calcium overload preventing activity was tested in SH-SY5Y neuroblastoma cell line by a fluorescence-based calcium assay. Among synthesized and tested compounds, 4a showed the highest calcium overload preventing activity (IC50=39μM) and 7e demonstrated the highest calcium channel inhibiting activity (EC50=0.2 nM). Asymmetric ester 7a exerted both substantial calcium channel blocking and calcium overload preventing activity.

  一种新型的不对称4-芳基-1,4-二氢吡啶（1,4-DHP）3,5-二酯衍生物及其对称类似物，包含了氨氯地平、利多卡因和脑坏死素的功能基团，已被合成。钙通道阻断活性在孤立的大鼠主动脉环模型中进行了评估。钙过载预防活性通过基于荧光的钙测定在SH-SY5Y神经母细胞瘤细胞系中进行了测试。在合成并测试的化合物中，4a表现出最高的钙过载预防活性（IC50=39μM），而7e显示出最高的钙通道抑制活性（EC50=0.2 nM）。不对称酯7a则同时展现了显著的钙通道阻断和钙过载预防活性。
• Effect of 4-aryl-2-methyl-5-nitro-1,4-dihydropyridine-3-carboxylates on the guinea pig papillary muscle and isolated human vena saphena magna that is used for coronary artery bypass grafting
  作者：Vida Garaliene、Vygantas Barsys、Antanas Mačys、Brigita Vigante、Aivars Krauze

  DOI：10.1016/j.ejmech.2011.07.018

  日期：2011.9

  4-dihydropyridine-3-carboxylate on the lengthening of cardiac APD were related to certain potassium channels (e.g., IK1, KATP and IK); and (iii) the modulation of the contraction-relaxation effects on isolated human vena saphena magna samples using three 5-nitro-substituted 1,4-dihydropyridine derivatives, displaying the positive inotropic and AP duration effects. Methods The experiments were conducted on isolated

  背景 这项研究的目的是估计：（i）5-硝基取代的1,4-二氢吡啶以及Bay K 8644（CAS [71145-03-4]）和CGP 28392（CAS [89289-93] -0]）对孤立的豚鼠乳头肌的心脏动作电位持续时间（APD）和等距收缩；（ii）4-（2-二氟甲氧基苯甲基）-2-甲基-5-硝基-1,4-二氢吡啶-3-羧酸2-丙氧基乙基酯对心脏APD延长的影响是否与某些钾通道有关（例如，I K1，K ATP和I K）；（iii）使用三种5-硝基取代的1,4-二氢吡啶衍生物对分离的人腔静脉大肠样品的收缩松弛作用的调节，表现出正性肌力和AP持续时间的作用。 方法 实验是从成年豚鼠的分离的人腔静脉大白鼠样品和乳头肌上进行的。分别使用力传感器和微电极技术记录等距收缩和AP。 结果 4-（2-二氟甲氧基苯基）-2-甲基-5-硝基-1,4-二氢吡啶-3-羧酸2-丙氧基乙酯以浓度依赖的方式显着增加