amlodipine malate

• 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: amlodipine malate
• 英文别名: 3-O-ethyl 5-O-methyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate;2-hydroxybutanedioic acid
• 化学式: C₄H₆O₅*C₂₀H₂₅ClN₂O₅
• 分子量: 542.971
• InChiKey: ICLGPDCMPQYWIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.17
• 重原子数：
  37
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  195
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  苹果酸 、 氨氯地平 以 甲醇 、 乙酸乙酯 为溶剂， 反应 1.75h， 生成 amlodipine malate
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF AMLODIPINE SALTS
  [FR] PROCEDE POUR L'ELABORATION DE SELS D'AMLODIPINE

  摘要：

  一种制备氨氯地平盐的方法包括将式（II）的化合物进行去保护反应，并将得到的氨氯地平游离碱转化为盐（1），而无需分离氨氯地平游离碱。最好制备马来酸盐、苯磺酸盐、苹果酸盐或富马酸盐。

  公开号：

  WO2005023769A1

文献信息

• [EN] COMBINATION OF (S)-AMLODIPINE AND A BETA-BLOCKER, AND METHODS FOR REDUCING HYPERTENSION<br/>[FR] COMBINAISON DE (S)-AMLODIPINE ET D'UN BETABLOQUANT, ET PROCEDES POUR LA REDUCTION DE L'HYPERTENSION
  申请人：SEPRACOR INC

  公开号：WO2005099699A1

  公开（公告）日：2005-10-27

  One aspect of the present invention relates to pharmaceutical compositions comprising optically pure (S)-amlodipine and a beta-blocker. In a preferred embodiment, the beta-blocker is atenolol or bisprolol. Another aspect of the present invention relates to pharmaceutical compositions consisting essentially of at least one pharmaceutically acceptable carrier, optically pure (S)-amlodipine and a beta-blocker. In a preferred embodiment, the beta-blocker is atenolol or bisoprolol. The pharmaceutical compositions of the invention are useful, e.g., in the treatment of hypertension. In addition, the present invention also relates to a method of treating a patient suffering from hypertension or a related cardiac disorder, comprising co-administering to a patient in need thereof a therapeutically effective amount of optically pure (S)-amlodipine and a beta-blocker. In certain embodiments of the compositions and methods, said optically pure (S)-amlodipine is optically pure (S)-amlodipine malate, or a polymorph, pseudopolymorph or solvate thereof.

  本发明的一个方面涉及包含光学纯（S）-氨氯地平和β受体阻断剂的制药组合物。在一个首选实施例中，β受体阻断剂为阿托伐他汀或比索洛尔。本发明的另一个方面涉及基本上由至少一种药用载体、光学纯（S）-氨氯地平和β受体阻断剂组成的制药组合物。在一个首选实施例中，β受体阻断剂为阿托伐他汀或比索洛尔。本发明的制药组合物可用于治疗高血压等疾病。此外，本发明还涉及一种治疗患有高血压或相关心脏疾病的患者的方法，包括向需要的患者共同给予光学纯（S）-氨氯地平和β受体阻断剂的治疗有效量。在某些组合物和方法的实施例中，所述的光学纯（S）-氨氯地平为光学纯（S）-氨氯地平苹果酸盐，或其多晶形、伪多晶形或溶剂化合物。
• (S)-amlodipine malate
  申请人：Laughlin M. Sharon

  公开号：US20060030602A1

  公开（公告）日：2006-02-09

  One aspect of the present invention relates to optically pure (S)-amlodipine malate. Another aspect of the present invention relates to (rac)-amlodipine malate. In a preferred embodiment, the compound is optically pure (S)-amlodipine L-malate. Another aspect of the present invention relates to a pharmaceutical composition comprising optically pure (S)-amlodipine malate. Another aspect of the present invention relates to a method of preparing optically pure (S)-amlodipine malate, comprising admixing optically pure (S)-amlodipine with malic acid. Another aspect of the present invention relates to the various polymorphic and solvated forms of optically pure (S)-amlodipine malate. In another prefered embodiment the invention relates to polymorphic and solvated forms A-G. The present invention also relates to a method of preparing optically pure (S)-amlodipine malate, comprising combining a salt of optically pure (S)-amlodipine with a malate salt to give optically pure (S)-amlodipine malate. In a preferred embodiment, the malate salt is an optically pure L-malate salt.

  本发明的一个方面涉及光学纯(S)-安托地平麻酸盐。本发明的另一个方面涉及(rac)-安托地平麻酸盐。在一个优选实施例中，该化合物是光学纯(S)-安托地平L-麻酸盐。本发明的另一个方面涉及包含光学纯(S)-安托地平麻酸盐的药物组合物。本发明的另一个方面涉及一种制备光学纯(S)-安托地平麻酸盐的方法，包括将光学纯(S)-安托地平与苹果酸混合。本发明的另一个方面涉及光学纯(S)-安托地平麻酸盐的各种多形态和溶剂化形式。在另一个优选实施例中，本发明涉及多形态和溶剂化形式A-G。本发明还涉及一种制备光学纯(S)-安托地平麻酸盐的方法，包括将光学纯(S)-安托地平的盐与麻酸盐结合以得到光学纯(S)-安托地平麻酸盐。在一个优选实施例中，麻酸盐是光学纯L-麻酸盐。
• (S)-Amlodipine malate
  申请人：Laughlin M. Sharon

  公开号：US20060035940A1

  公开（公告）日：2006-02-16

  One aspect of the present invention relates to optically pure (S)-amlodipine malate. Another aspect of the present invention relates to (rac)-amlodipine malate. In a preferred embodiment, the compound is optically pure (S)-amlodipine L-malate. Another aspect of the present invention relates to a pharmaceutical composition comprising optically pure (S)-amlodipine malate. Another aspect of the present invention relates to a method of preparing optically pure (S)-amlodipine malate, comprising admixing optically pure (S)-amlodipine with malic acid. Another aspect of the present invention relates to the various polymorphic and solvated forms of optically pure (S)-amlodipine malate. In another prefered embodiment the invention relates to polymorphic and solvated forms A-G. The present invention also relates to a method of preparing optically pure (S)-amlodipine malate, comprising combining a salt of optically pure (S)-amlodipine with a malate salt to give optically pure (S)-amlodipine malate. In a preferred embodiment, the malate salt is an optically pure L-malate salt.

  本发明的一个方面涉及光学纯(S)-安托地平苹果酸盐。本发明的另一个方面涉及(rac)-安托地平苹果酸盐。在一个优选实施例中，化合物为光学纯(S)-安托地平L-苹果酸盐。本发明的另一个方面涉及包括光学纯(S)-安托地平苹果酸盐的制药组合物。本发明的另一个方面涉及制备光学纯(S)-安托地平苹果酸盐的方法，包括混合光学纯(S)-安托地平和苹果酸。本发明的另一个方面涉及光学纯(S)-安托地平苹果酸盐的各种多晶型和溶剂化形式。在另一个优选实施例中，本发明涉及多晶型和溶剂化形式A-G。本发明还涉及一种制备光学纯(S)-安托地平苹果酸盐的方法，包括将光学纯(S)-安托地平的盐与苹果酸盐结合以得到光学纯(S)-安托地平苹果酸盐。在一个优选实施例中，苹果酸盐是光学纯L-苹果酸盐。
• Compositions comprising (S)-amlodipine malate and an angiotensin receptor blocker and methods of their use
  申请人：Grogan R. Donna

  公开号：US20050209288A1

  公开（公告）日：2005-09-22

  A pharmaceutical composition comprising enantiomerically pure (S)-amlodipine malate, an ARB and optional other active agents, and methods of treating, preventing and managing cardiovascular diseases and disorders, and symptoms thereof, using the composition, are disclosed.

  本发明公开了一种药物组合物，该组合物包含对映体纯的(S)-苹果酸氨氯地平、ARB 和任选的其他活性剂，以及使用该组合物治疗、预防和控制心血管疾病和失调及其症状的方法。
• SOLID PHARMACEUTICAL COMPOSITION COMPRISING AMLODIPINE AND LOSARTAN WITH IMPROVED STABILITY
  申请人：Hanmi Science Co., Ltd.

  公开号：EP2391348B1

  公开（公告）日：2014-08-27