4,4-dimethoxy-3-oxo-butyric acid cinnamyl ester | 215119-89-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4,4-dimethoxy-3-oxo-butyric acid cinnamyl ester
• 英文别名: (3-Phenyl-2-propene-1-yl) 4,4-dimethoxy-3-oxobutyrate；3-phenylprop-2-enyl 4,4-dimethoxy-3-oxobutanoate
• CAS: 215119-89-4
• 化学式: C₁₅H₁₈O₅
• 分子量: 278.305
• InChiKey: BVCCKAYVCVDRKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4,4-dimethoxy-3-oxo-butyric acid cinnamyl ester 在 哌啶 、 甲醇 、 ammonium acetate 、 sodium hydroxide 作用下， 以 异丙醇 、 苯 为溶剂， 生成 4-(3-chlorophenyl)-6-(dimethoxymethyl)-5-(3-phenylprop-2-enoxycarbonyl)-1,4-dihydropyridine-3-carboxylic acid
  参考文献：
  名称：

  Discovery and evaluation of selective N-type calcium channel blockers: 6-Unsubstituted-1,4-dihydropyridine-5-carboxylic acid derivatives

  摘要：

  A structure-activity relationship study of 6-unsubstituted-1,4-dihydropyridine and 2,6-unsubstituted-1,4-dihydropyridine derivatives was conducted in an attempt to discover N-type calcium channel blockers that were highly selective over L-type calcium channel blockers. Among the tested compounds, (+)-4-(3,5-dichloro-4-methoxy-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-cinnamyl ester was found to be an effective and selective N-type calcium channel blocker with oral analgesic potential. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.051
• 作为产物：
  描述：

  ethyl 4,4-dimethoxy-3-oxobutanoate 、 肉桂醇 以 甲苯 为溶剂， 生成 4,4-dimethoxy-3-oxo-butyric acid cinnamyl ester
  参考文献：
  名称：

  The structure–activity relationship study on 2-, 5-, and 6-position of the water soluble 1,4-dihydropyridine derivatives blocking N-type calcium channels

  摘要：

  In order to find an injectable and selective N-type calcium channel blocker, we have performed the structure-activity relationship (SAR) study on the 2-, 5-, and 6-position of 1,4-dihydropyridine-3-carboxylate derivative APJ2708 (2), which is a derivative of Cilnidipine and has L/N-type calcium channel dual inhibitory activities. As a consequence of the optimization, 6-dimethylacetal derivative 7 was found to have an effective inhibitory activity against N-type calcium channels with more than 170-fold lower activity for L-type channel compared to that of APJ2708. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.096

文献信息

• Dihydropyridine derivative
  申请人：Ajinomoto Co., Inc.

  公开号：US06995179B2

  公开（公告）日：2006-02-07

  Dihydropyridine derivatives of the following formula, analogs thereof and pharmaceutically acceptable salts thereof have an activity of selectively inhibiting the action of N-type calcium channel. They are used as remedies for various diseases relating to the N-type calcium channel such as encephalopathies caused by the ischemia in the acute phase after the onset of cerebral infarction, cerebral hemorrhage or the like, Alzheimer's disease, etc.

  以下公式的二氢吡啶衍生物、其类似物和药学上可接受的盐具有选择性抑制N型钙通道作用的活性。它们被用作治疗与N型钙通道相关的各种疾病，如脑梗死、脑出血等急性期缺血引起的脑病，阿尔茨海默病等。
• Asymmetric synthesis and biological evaluations of (+)- and (−)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels
  作者：Takashi Yamamoto、Seiji Ohno、Seiji Niwa、Munetaka Tokumasu、Masako Hagihara、Hajime Koganei、Shin-ichi Fujita、Tomoko Takeda、Yuki Saitou、Satoshi Iwayama、Akira Takahara、Seinosuke Iwata、Masataka Shoji

  DOI：10.1016/j.bmcl.2011.04.007

  日期：2011.6

  An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using t-butyl ester of L-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method, (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid cinnamyl ester was obtained and was characterized as a promising N-type calcium channel blocker with improved selectivity over L-type compared to its (-)- and racemic isomers. (C) 2011 Elsevier Ltd. All rights reserved.
• Discovery and evaluation of selective N-type calcium channel blockers: 6-Unsubstituted-1,4-dihydropyridine-5-carboxylic acid derivatives
  作者：Takashi Yamamoto、Seiji Niwa、Munetaka Tokumasu、Tomoyuki Onishi、Seiji Ohno、Masako Hagihara、Hajime Koganei、Shin-ichi Fujita、Tomoko Takeda、Yuki Saitou、Satoshi Iwayama、Akira Takahara、Seinosuke Iwata、Masataka Shoji

  DOI：10.1016/j.bmcl.2012.04.051

  日期：2012.6

  A structure-activity relationship study of 6-unsubstituted-1,4-dihydropyridine and 2,6-unsubstituted-1,4-dihydropyridine derivatives was conducted in an attempt to discover N-type calcium channel blockers that were highly selective over L-type calcium channel blockers. Among the tested compounds, (+)-4-(3,5-dichloro-4-methoxy-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-cinnamyl ester was found to be an effective and selective N-type calcium channel blocker with oral analgesic potential. (C) 2012 Elsevier Ltd. All rights reserved.
• The structure–activity relationship study on 2-, 5-, and 6-position of the water soluble 1,4-dihydropyridine derivatives blocking N-type calcium channels
  作者：Takashi Yamamoto、Seiji Niwa、Seiji Ohno、Munetaka Tokumasu、Yoko Masuzawa、Chika Nakanishi、Akira Nakajo、Tomoyuki Onishi、Hajime Koganei、Shin-ichi Fujita、Tomoko Takeda、Morikazu Kito、Yukitsugu Ono、Yuki Saitou、Akira Takahara、Seinosuke Iwata、Masataka Shoji

  DOI：10.1016/j.bmcl.2008.07.096

  日期：2008.9

  In order to find an injectable and selective N-type calcium channel blocker, we have performed the structure-activity relationship (SAR) study on the 2-, 5-, and 6-position of 1,4-dihydropyridine-3-carboxylate derivative APJ2708 (2), which is a derivative of Cilnidipine and has L/N-type calcium channel dual inhibitory activities. As a consequence of the optimization, 6-dimethylacetal derivative 7 was found to have an effective inhibitory activity against N-type calcium channels with more than 170-fold lower activity for L-type channel compared to that of APJ2708. (C) 2008 Elsevier Ltd. All rights reserved.