isobutyl 3-aminocrotonate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: isobutyl 3-aminocrotonate
• 英文别名: 3-aminocrotonic acid isobutyl ester；2-methylpropyl (Z)-3-aminobut-2-enoate
• 化学式: C₈H₁₅NO₂
• 分子量: 157.213
• InChiKey: DFLRRTPSYIFGOC-DAXSKMNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  isobutyl 3-aminocrotonate 以 异丙醇 为溶剂， 生成 3-O-[2-[3,3-diphenylpropyl(methyl)amino]ethyl] 5-O-(2-methylpropyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Asymmetric N-(3,3-diphenylpropyl)aminoalkyl esters of 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acids with antihypertensive activity

  摘要：

  A series of asymmetric 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates characterized by the presence of a 3,3-diphenyl-propylamino moiety in one of the ester groups were synthesized. They exhibited remarkable antihypertensive activity in spontaneously hypertensive rats as well as affinity for the 1,4-dihydropyridines binding site labelled by H-3-nitrendipine in the calcium channel. Introduction of this bulky and lipophilic amine confers to the whole series an elevated level of antihypertensive activity and a long duration of action, a structure-dependent modulation of the activity being found only in the subset characterized by the presence of a branched propylene bridge between the ester and the amino groups. The presence of the amino group is essential for oral activity. Out of this series, compound 9u (Rec 15/2375-lercanidipine) was selected for clinical development and obtained marketing authorization as an antihypertensive in several countries. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80015-9
• 作为产物：
  描述：

  乙酰乙酸异丁酯 在 氨 作用下， 以 二氯甲烷 为溶剂， 以85%的产率得到isobutyl 3-aminocrotonate
  参考文献：
  名称：

  Asymmetric N-(3,3-diphenylpropyl)aminoalkyl esters of 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acids with antihypertensive activity

  摘要：

  A series of asymmetric 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates characterized by the presence of a 3,3-diphenyl-propylamino moiety in one of the ester groups were synthesized. They exhibited remarkable antihypertensive activity in spontaneously hypertensive rats as well as affinity for the 1,4-dihydropyridines binding site labelled by H-3-nitrendipine in the calcium channel. Introduction of this bulky and lipophilic amine confers to the whole series an elevated level of antihypertensive activity and a long duration of action, a structure-dependent modulation of the activity being found only in the subset characterized by the presence of a branched propylene bridge between the ester and the amino groups. The presence of the amino group is essential for oral activity. Out of this series, compound 9u (Rec 15/2375-lercanidipine) was selected for clinical development and obtained marketing authorization as an antihypertensive in several countries. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80015-9

文献信息

• 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。
• Synthesis and Antihypertensive Activities of New 1,4-Dihydropyridine Derivatives Containing a Nitrooxy Moiety at the 3-Ester Position.
  作者：Toshihisa OGAWA、Atsuro NAKAZATO、Katsuharu TSUCHIDA、Katsuo HATAYAMA

  DOI：10.1248/cpb.41.108

  日期：——

  The synthesis of a new series of dihydropyridines containing a nitrooxy mojety at the 3-ester position is described.The antihypertensive activity of the compounds was examined and compared with that of nifedipine; some of them were relatively potent. The structure-activity relationship is also discussed.

  研究合成了一系列在3-酯位含有硝氧基的二氢吡啶类新化合物。这些化合物的降压活性经检验并与尼非地平相比较；其中一些相对具有较强的活性。同时还讨论了结构与活性之间的关系。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF PURE NISOLDIPINE<br/>[FR] PROCEDE AMELIORE DE PREPARATION DE NISOLDIPINE PURE
  申请人：SANMAR SPECIALITY CHEMICALS LT

  公开号：WO2005023768A1

  公开（公告）日：2005-03-17

  Nisoldipine is prepared by the process according to this invention by cyclocondensing 3-Aminocrotonoic acid isobutyl ester with 2-(2-nitrobenzylidene)-3-oxo-butyric acid methyl ester in the presence of a water immiscible organic solvent such as toluene and an aprotic organic solvent. The reaction product is recovered after refluxing with diisopropyl ether. Water miscible aprotic solvent may be selected from ethers and glycol ethers.

  尼索地平是通过本发明的方法制备的，该方法是通过在水不相容的有机溶剂（如甲苯）和无极性有机溶剂的存在下，将3-氨基巴氨基丙烯酸异丁酯与2-(2-硝基苯甲亚甲基)-3-氧代丁酸甲酯环合反应。在与二异丙基醚回流后，可以回收反应产物。水溶性无极性溶剂可以选择从醚类和乙二醇醚中选取。
• [EN] PROCESS FOR THE PREPARATION OF 4 -SUBSTITUTED -1, 4-DIHYDROPYRIDINES<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE 1,4-DIHYDROPYRIDINES SUBSTITUÉES EN POSITION 4
  申请人：ARCH PHARMALABS LTD

  公开号：WO2012123966A1

  公开（公告）日：2012-09-20

  4-Substituted-l,4-dihydropyridines of formula I are prepared by a cycloaddition reaction in which the cyclization is driven to completion at ambient temperature optionally in water without any catalyst. For exemplary purposes, the invention is described in particular detail with respect to the preparation of felodipine of formula II. Felodipine, a vasodilator, is prepared by a cycloaddition reaction of alkyl 3- aminocrotonate with dichlorobenzylidene under reaction conditions whereby the product crystallizes out of the reaction solution and may be directly isolated by filtration.

  通过环加成反应制备公式I的4-取代-1,4-二氢吡啶，该环化反应在室温下可在水中无需任何催化剂的情况下完全进行。为了举例说明，本发明特别详细地描述了制备公式II的非洛地平的方法。非洛地平是一种血管扩张剂，通过烷基3-氨基丙烯酸酯与二氯苯甲醛进行环加成反应制备，反应条件下产物结晶出来并可通过过滤直接分离。
• Synthesis of dialkyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates and alkyl 1,4-dihydro-2,6-dimethyl-3-nitropyridine-5-carboxylates possessing a c-4 2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl (uracil) substituent to determine calcium channel modulation structure-activity relationships
  作者：Afshin Fassihi、Carlos Velazquez、Edward E. Knaus

  DOI：10.1002/jhet.5570410218

  日期：2004.3

  C-4 aryl or heteroaryl substituents present in 1,4-dihydropyridine calcium channel modulators since diisopropyl 1,4-dihydro-2,6-dimemyl-4-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)pyridine-3,5-dicarboxylate (3b) and isobutyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2,4-dloxo-1,2,3,4-tetrahydropyrimidin-5-yl)pyridine-5-carboxylate (6c) did not exhibit any in vitro calcium channel antagonist activity using

  5-甲氧尿嘧啶（1）与乙酰乙酸甲酯，异丙基或异丁酯（2a-c）在氢氧化铵存在下的汉茨缩合反应得到各自的二烷基1,4-二氢-2,6-二甲基-4-（2,4 -dloxo-1,2,3,4，-四氢嘧啶-5-基）吡啶-3,5-二羧酸酯（3a-c）。一组烷基1,4-二氢-2,6-二甲基-3-硝基-4-（2,4-二氧-1,2,3,4-四氢嘧啶-5-基）吡啶-5-羧酸酯（6a -c）也使用改良的Hantzsch反应制备，该反应涉及5-甲酰尿嘧啶与硝基丙酮和3-氨基巴豆酸甲酯，异丙基或异丁酯（5a-c）的缩合。对于存在于1,4-二氢吡啶钙通道调节剂中的传统C-4芳基或杂芳基取代基，C-4 2,4-二氧-1,2,3,4-四氢嘧啶-5-基不是合适的生物甾体，因为1,4-二氢-2,6-二异丙基-4-（2,4-二氧-1,2,3,4-四氢嘧啶-5-基）吡啶-3,5-二羧酸二异丙酯（3b）和异丁基1， 4-二氢-2,6-二甲基-3-硝基-4-（2