培哚普利精氨酸 | 612548-45-5

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 精氨酸类衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 培哚普利精氨酸
• 英文名称: perindopril L-arginine
• 英文别名: perindopril L-arginine salt；perindopril (L)-arginine salt；perindopril (L)-arginine；Perindopril arginine；(2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid;(2S)-2-amino-5-(diaminomethylideneamino)pentanoic acid
• CAS: 612548-45-5
• 化学式: C₆H₁₄N₄O₂*C₁₉H₃₂N₂O₅
• 分子量: 542.676
• InChiKey: RYCSJJXKEWBUTI-YDYAIEMNSA-N

物化性质

• 熔点：
  >116°C (dec.)
• 溶解度：
  DMSO（少许）、甲醇（少许）、水（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  0.39
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  224
• 氢给体数：
  6
• 氢受体数：
  10

制备方法与用途

用途

培哚普利精氨酸是培哚普利的一种复合形式，具备抗高血压、心血管保护以及抗血栓的作用。它已经被证实以中性复合物的形式存在。

反应信息

• 作为反应物：
  描述：

  培哚普利精氨酸 在 水 、 氢氯噻嗪 作用下， 反应 250.0h， 生成 培哚普利拉内酰胺A 、 培哚普利
  参考文献：
  名称：

  Impact of hydrochlorothiazide on the stability of two perindopril salts. Evaluation of the interaction with HPLC and ESI LC/MS methods

  摘要：

  Perindopril (PER) belongs to the group of the angiotensin-converting enzyme inhibitors and is widely prescribed antihypertensive drug. It can be used in monotherapy or in combination therapy for example with hydrochlorothiazide (HTH). As on the market there is no pharmaceutical formulation containing both drugs and in literature has not been reported any work about effect of HTH on PER degradation process, the primary objective of this study was the assessment of stability of two salts of perindopril n tert-butylamine (PERt) and arginine (PERa) in a mixtures model with HTH in different relative humidities and constant temperature. The objective of the study was establishing the mechanisms of drug decomposition in the presence of HTH. Results were achieved using the high-performance liquid chromatography (RP-HPLC). The degradation rate constants for mixtures and pure substances were calculated. Decomposition products have been analyzed by ESI LC/MS and the decomposition mechanism for each salt has been proposed. The degradation of PERt in the presence of HTH took place according to autocatalytic reaction kinetic mechanism, described mathematically by ProutTompkins equation, and the decomposition process leads to hydrolysis. HTH in the model mixture with PERa generates a first-order kinetic model of the decomposition reaction, and there are two main products of decomposition: product of hydrolysis and diketopiperazine. Our study showed that HTH has statistically significant positive impact on both salts. It can be suggested that PERt or PERa and HTH can be formulated together, hence there is no negative interaction between the drugs.

  DOI：

  10.32383/appdr/82922
• 作为产物：
  描述：

  L-精氨酸 、 培哚普利 在 indicated solvents 作用下， 以 水 为溶剂， 反应 13.5h， 生成 培哚普利精氨酸
  参考文献：
  名称：

  Polymorphic forms of perindopril (L)-arginine and process for the preparation thereof

  摘要：

  本发明涉及Perindopril (L)-Arginine的新型和稳定的多晶形式，称为γ形式和非晶形式，以及它们的制备过程。本发明还提供了新的多晶形式γ，具有更好的耐热性和耐湿性，并且可以通过高效、经济和可重复的过程进行大规模制备。

  公开号：

  US08686161B2

文献信息

• Alpha Crystalline form of the Arginine salt of Perindopril, a Process for its Preparation and Pharmceutical Compositions Containing it.
  申请人：Coquerel Gerald

  公开号：US20090203758A1

  公开（公告）日：2009-08-13

  α-crystalline form of the compound of formula (I): characterised by its powder X-ray diffraction diagram. Medicinal products containing the same which are useful as inhibitors of angiotensin I converting enzyme.

  公式（I）化合物的α-晶体形式：其粉末X射线衍射图谱为特征。含有相同晶体形式的药物可用作抑制血管紧张素I转换酶的药物。
• PROCESS FOR THE PREPARATION OF THE L-ARGININE SALT OF PERINDOPRIL
  申请人：Les Laboratoires Servier

  公开号：US20130178635A1

  公开（公告）日：2013-07-11

  Process for the preparation of the compound of formula (I):

  制备式(I)化合物的过程：
• DELTA CRYSTALLINE FORM OF THE ARGININE SALT OF PERINDOPRIL, A PROCESS FOR ITS PREPARATION, AND PHARMACEUTICAL COMPOSITIONS CONTAINING IT
  申请人：LES LABORATOIRES SERVIER

  公开号：US20130178464A1

  公开（公告）日：2013-07-11

  Delta crystalline form of the compound of formula (I): characterised by its X-ray powder diffraction diagram. Medicinal products containing the same which are useful in the treatment of cardiovascular diseases.

  化合物公式(I)的Delta晶体形式：其特征为其X射线粉末衍射图谱。含有该晶体形式的药物制剂在心血管疾病治疗中有用。
• AMORPHOUS FORM OF AN L-ARGININE SALT OF PERINDOPRIL AND PROCESSES FOR PREPARATION THEREOF
  申请人：WEERATUNGA Gamini

  公开号：US20100056802A1

  公开（公告）日：2010-03-04

  In illustrative embodiments, there is provided an amorphous form of L-arginine salt of perindopril which may be particularly suitable for pharmaceutical applications, and processes for preparing said form.

  在说明性实施例中，提供了一种L-精氨酸盐酸珀卓尔的非晶态形式，该形式可能特别适用于制药应用，并提供了制备该形式的工艺。
• Amorphous form of an L-arginine salt of perindopril and processes for preparation thereof
  申请人：Apotex Pharmachem Inc.

  公开号：EP2161257A1

  公开（公告）日：2010-03-10

  In illustrative embodiments, there is provided an amorphous form of L-arginine salt of perindopril which may be particularly suitable for pharmaceutical applications, and processes for preparing said form.

  在说明性实施例中，提供了一种L-精氨酸盐酸珀卓尔的非晶态形式，该形式可能特别适用于制药应用，并提供了制备该形式的工艺。