培哚普利拉内酰胺A | 129970-99-6

• 物质功能分类: 生物 - 细胞培养 - 添加剂
• 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: 培哚普利拉内酰胺A
• 中文别名: 培哚普利杂质C
• 英文名称: (2S)-2-[(3S,5aS,9aS,10aS)-3-methyl-1,4-dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl]pentanoic acid
• 英文别名: Perindoprilat lactam A；(2S)-2-[(3S,5aS,9aS,10aS)-3-methyl-1,4-dioxo-5a,6,7,8,9,9a,10,10a-octahydro-3H-pyrazino[1,2-a]indol-2-yl]pentanoic acid
• CAS: 129970-99-6
• 化学式: C₁₇H₂₆N₂O₄
• 分子量: 322.404
• InChiKey: GBVXUKWRYVJUFG-PEDHHIEDSA-N

物化性质

• 熔点：
  >115°C (dec.)
• 沸点：
  560.3±50.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  77.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• WGK Germany：
  3

反应信息

• 作为产物：
  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

文献信息

• A pharmaceutical composition comprising perindopril
  申请人：LEK Pharmaceuticals d.d.

  公开号：EP1815857A1

  公开（公告）日：2007-08-08

  The present invention provides a stable pharmaceutical composition comprising an inclusion complex of perindopril, a microcrystalline cellulose having a low moisture content and/or a silicified microcrystalline cellulose having a low moisture content, and optionally other pharmaceutically acceptable excipients.

  本发明提供了一种稳定的药物组合物，它包含培哚普利的包合物、含水量低的微晶纤维素和/或含水量低的硅化微晶纤维素，以及可选的其他药学上可接受的赋形剂。
• PHARMACEUTICAL COMPOSITION COMPRISING PERINDOPRIL OR ITS SALTS
  申请人：LEK Pharmaceuticals d.d.

  公开号：EP1937216A1

  公开（公告）日：2008-07-02
• A PHARMACEUTICAL COMPOSITION COMPRISING PERINDOPRIL
  申请人：LEK Pharmaceuticals d.d.

  公开号：EP1981496A1

  公开（公告）日：2008-10-22
• PERINDOPRIL FORMULATIONS
  申请人：Subramony Janardhanan Anand

  公开号：US20100076052A1

  公开（公告）日：2010-03-25

  Pharmaceutical formulations comprising perindopril or its salts, isomers, enantiomers, polymorphs, metabolites, solvates, hydrates, and mixtures thereof, and at least one surface stabilizer. Also disclosed are methods of stabilizing perindopril in the formulations, and polyoxyethylene-polyoxypropylene block copolymers as surface stabilizers.
• [EN] PHARMACEUTICAL PREPARATION COMPRISING PERINDOPRIL ERBUMINE AND METHOD OF PREPARATION AND STABILISATION THEREOF<br/>[FR] PREPARATION PHARMACEUTIQUE CONTENANT DE LA PERINDOPRIL ERBUMINE ET PROCEDE DE PREPARATION ET DE STABILISATION ASSOCIE
  申请人：VULM A S

  公开号：WO2006101462A2

  公开（公告）日：2006-09-28

  [EN] The subject matter of the invention is a pharmaceutical preparation comprising perindopril erbumine in a stable form within the rage 1 to 40 % by weight and at least one excipient and/or a mixture of excipients within the range 1 % - 99 % by weight, whereas at least one excipient is a substance of basic character maintaining pH 7.1 to 14. The subject matters of the invention are also a method of preparing, stabilising and packing of an oral pharmaceutical preparation in the dosage form of tablets, and/or coated tablets, and/or capsules which is used as an oral therapeutic of hypertension. The principle of manufacturing method consists in preparation of a compound comprising an alkalising excipient by dry mixing of powder components, and/or briqueting, and/or compacting, and modification of particle size of a compound. The compound prepared in this way may be used for compression of tablet cores, and/or tablets, and/or micro-tablets, and/or preparation of pellets, and/or micro-pellets, and/or powders and/or granules, and/or fill in capsules.
  [FR] L'invention concerne une préparation pharmaceutique contenant de la périndopril erbumine sous forme stable dans une quantité comprise entre 1 et 40 % en poids, et au moins un excipient et/ou un mélange d'excipients dans une quantité comprise entre 1 et 99 % en poids, au moins un excipient étant une substance de caractère basique maintenant un pH de 7,1 à 14. L'invention concerne également un procédé de préparation, de stabilisation et d'emballage d'une préparation pharmaceutique orale sous forme dosifiée de comprimés et/ou de comprimés enrobés et/ou de gélules, utilisée comme agent thérapeutique oral dans le traitement de l'hypertension. Le procédé de fabrication consiste à préparer un composé contenant un excipient alcalisant par mélange sec et/ou briquetage et/ou compactage de composants en poudre, et à modifier la dimension des particules du composé. Le composé ainsi obtenu peut être utilisé dans la compression de noyaux de comprimés et/ou de comprimés et/ou de micro-comprimés, et/ou dans la préparation de pastilles et/ou de micro-pastilles et/ou de poudres et/ou de granulés, et/ou dans le remplissage de gélules.