2-[(2-氨基乙氧基)甲基]-4-(2-氯苯基)-6-甲基-1,4-二氢吡啶-3,5-二甲酸二甲酯 | 140171-66-0

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 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
• 中文名称: 2-[(2-氨基乙氧基)甲基]-4-(2-氯苯基)-6-甲基-1,4-二氢吡啶-3,5-二甲酸二甲酯
• 中文别名: 氨氯地平杂质F
• 英文名称: dimethyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate
• 英文别名: amlodipine；2-(2-amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester；Dimethyl 2-((2-aminoethoxy)methyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate；dimethyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 140171-66-0
• 化学式: C₁₉H₂₃ClN₂O₅
• 分子量: 394.855
• InChiKey: UDSAEMGNQXMCDF-UHFFFAOYSA-N

物化性质

• 熔点：
  42-45°C
• 沸点：
  516.6±50.0 °C(Predicted)
• 密度：
  1.247±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  99.9
• 氢给体数：
  2
• 氢受体数：
  7

制备方法与用途

Amlodipine besylate impurity F，又称Amlodipine dimethyl ester，是一种生物化学物质。

反应信息

• 作为反应物：
  描述：

  2-[(2-氨基乙氧基)甲基]-4-(2-氯苯基)-6-甲基-1,4-二氢吡啶-3,5-二甲酸二甲酯 在 potassium tert-butylate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 3-ethyl 5-methyl 4-(2-chlorophenyl)-2-((2-((5R,8S)-2-(2-((4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridin-2-yl)methoxy)ethyl)-1-hydroxy-3-oxo-5,8-diphenyl-2-azabicyclo[2.2.2]octane-4-carboxamido)ethoxy)methyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  阴离子级联反应III：3-异奎宁环酮桥联多环内酰胺的合成

  摘要：

  桥连多环内酰胺是有机功能材料、天然产物和药物中的重要结构单元。开发了一种灵活高效的阴离子级联反应，用于从容易获得的丙二酰胺和 1,4-二烯-3-酮制备桥联多环内酰胺。在t BuOK 存在下，在市售 EtOH 溶剂中，在 60 °C 下，通过串联亲核序列以良好至优异的产率合成了各种高度取代的桥联多环内酰胺。值得注意的是，简单的反应可以在克规模上进行。从机理上讲，双迈克尔加成反应和半胺化反应参与串联转化。

  DOI：

  10.1016/j.cclet.2023.109184
• 作为产物：
  描述：

  β-氨基巴豆酸甲酯 在 甲胺 作用下， 生成 2-[(2-氨基乙氧基)甲基]-4-(2-氯苯基)-6-甲基-1,4-二氢吡啶-3,5-二甲酸二甲酯
  参考文献：
  名称：

  Long-acting dihydropyridine calcium antagonists. 9. Structure activity relationships around amlodipine

  摘要：

  The preparation of a range of 1,4-dihydropyridine analogues of amlodipine has been undertaken and their calcium antagonist activities on rat aorta have been evaluated. Increasing the size of the C5 ester group dramatically reduces calcium antagonist activity, a trend which would be compatible with the carbonyl group of that ester binding to the DHP receptor. Amlodipine analogues with extended C3 ester substituents also have lower potency than amlodipine, possibly because of disruption of a favourable interaction between the protonated amino group on the 2-substituent and the DHP receptor. Replacement of the 6-methyl substituent in amlodipine by alkoxyalkyl groups or electron-withdrawing groups is also detrimental to calcium antagonist activity.

  DOI：

  10.1016/0223-5234(91)90132-7

文献信息

• [EN] DIHYDROPYRIDINE COMPOUNDS HAVING SIMULTANEOUS ABILITY TO BLOCK L-TYPE CALCIUM CHANNELS AND TO INHIBIT PHOSPHODIESTERASE TYPE 3 ACTIVITY<br/>[FR] COMPOSES DE DIHYDROPYRIDINE PRESENTANT A LA FOIS LA CAPACITE DE BLOQUER DES CANAUX CALCIQUES DE TYPE L ET LA CAPACITE D'INHIBER L'ACTIVITE DE TYPE 3 DE LA PHOSPHODIESTERASE
  申请人：ARTESIAN THERAPEUTICS INC

  公开号：WO2004033444A1

  公开（公告）日：2004-04-22

  The present invention provides compounds that possess inhibitory activity against PDE-3 and L-type calcium channels. The present invention further provides pharmaceutical compositions comprising such compounds and methods of using such compounds for treating cardiovascular disease, stroke, epilepsy, ophthalmic disorder or migraine.

  本发明提供了具有对PDE-3和L型钙通道具有抑制活性的化合物。本发明还提供了包含这些化合物的药物组合物以及使用这些化合物治疗心血管疾病、中风、癫痫、眼科疾病或偏头痛的方法。
• [EN] TWO CRYSTALLINE HYDRATE FORMS OF AMLODIPINE BENZENESULFONATE OF HIGH PURITY, PROCESSES FOR THEIR PREPARATION AND USE<br/>[FR] DEUX FORMES DIHYDRATE CRISTALLIN DE BENZENESULFONATE D'AMLODIPINE A PURETE ELEVEE, LEURS PROCEDES DE PREPARATION ET LEUR UTILISATION
  申请人：LEK PHARMACEUTICALS

  公开号：WO2003101965A1

  公开（公告）日：2003-12-11

  The novel crystalline amlodipine benzenesulfonate dihydrate of high purity is disclosed, as well as the process for preparation of the novel crystalline amlodipine benzenesulfonate dihydrate of high purity and the crystalline amlodipine benzenesulfonate monohydrate of high purity, suitable for the preparation of pharmaceutical formulations for the treatment of cardiac diseases or hypertension, and their use as intermediate compounds in the improved process of purification of the nonhydrate benzenesulfonate (besylate) salt of amlodipine.The process for preparation of the crystalline amlodipine benzenesulfonate dihydrate is carried in the way that from the C1-C5 alcoholic solution of amlodipine benzenesulfonate with water while stirring at a temperature of 20°C or lower the crystals of pure amlodipine benzenesulfonate dihydrate are separated, and isolated.The process for preparation of the crystalline amlodipine benzenesulfonate monohydrate is carried in the way that from the C1-C5 alcoholic solution of amlodipine benzenesulfonate with water while stirring at a temperature of 30°C or higher the crystals of pure amlodipine benzenesulfonate monohydrate are separated, and isolated.

  揭示了高纯度的新型结晶氨氯地平苯磺酸苄水合物，以及制备高纯度的新型结晶氨氯地平苯磺酸苄水合物和高纯度的结晶氨氯地平苯磺酸苄单水合物的过程，适用于制备用于治疗心脏疾病或高血压的药物配方，并将它们用作改进的非水合物苯磺酸苄酯盐（besylate）的氨氯地平纯化过程中的中间化合物。制备结晶氨氯地平苯磺酸苄水合物的过程是这样进行的：在20°C或更低温度下，从氨氯地平苯磺酸苄的C1-C5醇溶液中加入水搅拌，分离并提取出纯净的氨氯地平苯磺酸苄水合物晶体。制备结晶氨氯地平苯磺酸苄单水合物的过程是这样进行的：在30°C或更高温度下，从氨氯地平苯磺酸苄的C1-C5醇溶液中加入水搅拌，分离并提取出纯净的氨氯地平苯磺酸苄单水合物晶体。
• Compounds having simultaneous ability to block L-type calcium channels and to inhibit phosphodiesterase type 3 activity
  申请人：ARTESIAN THERAPEUTICS, INC.

  公开号：US20040242648A1

  公开（公告）日：2004-12-02

  The present invention provides compounds that possess inhibitory activity against PDE-3 and L-type calcium channels. The present invention further provides pharmaceutical compositions comprising such compounds and methods of using such compounds for treating cardiovascular disease, stroke, epilepsy, ophthalmic disorder or migraine.

  本发明提供了具有对PDE-3和L型钙通道的抑制活性的化合物。本发明还提供了包含这种化合物的药物组合物和使用这种化合物治疗心血管疾病、中风、癫痫、眼科疾病或偏头痛的方法。
• PROCESS FOR MAKING AMLODIPINE, DERIVATIVES THEREOF, AND PRECURSORS THEREFOR
  申请人：Slanina Pavel

  公开号：US20080070789A1

  公开（公告）日：2008-03-20

  Impurities associated with the commercial production of amlodipine are identified along with methods of assaying the same.

  商业生产氨氯地平时发现了杂质，并提出了检测方法。
• C-Nitroso compounds and use thereof
  申请人：Stamler S. Jonathan

  公开号：US20070258942A1

  公开（公告）日：2007-11-08

  A C-nitroso compound having a molecular weight ranging from 225 to 1,000 (from 225 to 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to about 20, vascular relaxing effect is obtained at nanomolar concentrations without ghitathione. In another embodiment, a biocompatible polymer incorporates a C-nitroso moiety.

  一种分子量范围为225至1,000（口服为225至600）的C-亚硝基化合物，其基础单体中亚硝基基团连接到三级碳上，通过对pKa小于约25的碳酸的亚硝基化获得，可用作NO供体。当该化合物由pKa小于约10的碳酸获得时，在微摩尔浓度下使用可提供血管松弛作用，且该活性在谷胱甘肽的作用下可在纳摩尔浓度下获得。当该化合物由pKa约为15至20的碳酸获得时，可在纳摩尔浓度下获得血管松弛作用而无需谷胱甘肽。在另一实施例中，一种生物相容性聚合物包含C-亚硝基基团。