乙基(2R)-2-[(3S,5aS,8aS,9aS)-3-甲基-1,4-二氧代十氢-2H-环戊二烯并[4,5]吡咯并[1,2-a]吡嗪-2-基]-4-苯基丁酸酯 | 108731-95-9

• 物质功能分类: 医药中间体 - 哌嗪类化合物
• 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: 乙基(2R)-2-[(3S,5aS,8aS,9aS)-3-甲基-1,4-二氧代十氢-2H-环戊二烯并[4,5]吡咯并[1,2-a]吡嗪-2-基]-4-苯基丁酸酯
• 中文别名: 雷米普利二酮哌嗪；噻唑并[5,4-b]吡啶-2(1H)-酮,5-甲氧基-,腙(9CI)；雷米普利EP杂质D
• 英文名称: ramipril dioxopiperazine
• 英文别名: ramipril diketopiperazine；ethyl (2S)-2-[(2S,6S,8S,11S)-11-methyl-9,12-dioxo-1,10-diazatricyclo[6.4.0.02,6]dodecan-10-yl]-4-phenylbutanoate
• CAS: 108731-95-9
• 化学式: C₂₃H₃₀N₂O₄
• 分子量: 398.502
• InChiKey: KOVMAAYRBJCASY-JBDAPHQKSA-N

物化性质

• 沸点：
  597.4±50.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：可溶，乙醇：可溶

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  乙基(2R)-2-[(3S,5aS,8aS,9aS)-3-甲基-1,4-二氧代十氢-2H-环戊二烯并[4,5]吡咯并[1,2-a]吡嗪-2-基]-4-苯基丁酸酯 、 去氢氨氯地平草酸酯 以to get a final concentration of 500 ppm of Ramipril and Amlodipine的产率得到雷米普利
  参考文献：
  名称：

  Stable pharmaceutical compositions of calcium channel blocker and an ACE inhibitor

  摘要：

  本发明涉及一种稳定的药物组合物，包含氨氯地平和ACE抑制剂，其中两种活性成分未被物理分离，且该组合物的pH值大于6.0。本发明还涉及一种制备过程以及使用该组合物的方法。

  公开号：

  US20080096863A1
• 作为产物：
  描述：

  雷米普利 在 盐酸 、 水 作用下， 以 甲醇 为溶剂， 反应 30.0h， 生成 乙基(2R)-2-[(3S,5aS,8aS,9aS)-3-甲基-1,4-二氧代十氢-2H-环戊二烯并[4,5]吡咯并[1,2-a]吡嗪-2-基]-4-苯基丁酸酯
  参考文献：
  名称：

  STRESS DEGRADATION STUDIES OF RAMIPRIL BY A VALIDATED STABILITY-INDICATING LIQUID CHROMATOGRAPHIC METHOD

  摘要：

  Ramipril is an angiotensin-converting enzyme inhibitor which has chemical structure susceptible to degradation, therefore in this work forced degradation studies of ramipril were carried out by a developed and validated stability-indicating liquid chromatographic method. Stress testing was performed on drug substance under hydrolysis (0.1 N HCl, water and 0.1 N NaOH), oxidation (3% H2O3,), heat (70 degrees C) and photolysis (UV and VIS radiation). The drug was degraded under acidic, neutral, alkaline, oxidation and thermal stress conditions but it was stable under photolysis. Chromatographic separation of ramipril from its degradation products was achieved on a RP-18 column, using a mobile phase consisting of methanol - tetrahydrofuran - phosphate buffer (pH 2.4; 0.01M) (55:5:40, v/v/v) at a flow rate of 1.0 mL min(-1) and UV detection at 215 nm. The assay was linear for ramipril concentrations of 50-300 mu g/mL. The developed method was stability indicating, specific, accurate and precise for ramipril determination. This method was used to quantify ramipril in tablets. The results showed that the method described here is suitable for quantitative determination and the stability study of ramipril.

  DOI：

  10.4067/s0717-97072010000400008

文献信息

• Two validated stability-indicating chromatographic methods for the separation of two anti-hypertensive combinations in the presence of their degradation products or impurities
  作者：Noha Samy Mostafa、Ghada AbdElHamid、Hala Elsayed Zaazaa、Sawsan Mohamed Amer

  DOI：10.1007/s11696-019-00792-z

  日期：2019.10

  of the mixtures were detected at 218 nm. For the best separation of the mentioned components different parameters were examined and optimized. The two suggested methods were validated in compliance with the ICH guidelines and were successfully applied for the quantification of the cited components in presence of their obtained degradation products as well as in their commercial pharmaceutical formulations

  开发，优化和验证了两种RP-HPLC方法，用于在降解产物或杂质存在及其药物制剂中测定两种不同的抗高血压组合。第一种混合物是雷米普利（RAM）和苯磺酸氨氯地平（AML）[混合物I]，而第二种混合物是雷米普利（RAM），阿托伐他汀（ATV）和阿司匹林（ASP）[混合物II]。提议的组合已在X桥C 18上成功分离色谱柱（250×4.6 mm内径，5 µm ps），使用0.05 M磷酸盐缓冲液-乙腈-THF（60：40：0.1％体积）pH 2.5的流动相和由乙腈-0.05 M磷酸盐形成的等度流动相混合物（I）和（II）的缓冲液-THF（60：40：0.1体积％）pH 2.5，流速分别为1 mL / min和1.2 mL / min。在218 nm处检测到混合物中的有害成分。为了最好地分离上述组分，检查并优化了不同的参数。两种建议的方法均已按照ICH指南进行了验证，并成功地用于存在的降解产物及其商业
• PREPARATION OF RAMIPRIL AND STABLE PHARMACEUTICAL COMPOSITIONS
  申请人：Bolugoddu Vijayabhaskar

  公开号：US20070232680A1

  公开（公告）日：2007-10-04

  A process for preparing ramipril, and stable pharmaceutical compositions containing ramipril.

  一种制备雷米普利以及含有雷米普利的稳定药物组合物的方法。
• Teetz; Geiger; Henning, Arzneimittel-Forschung/Drug Research, 1984, vol. 34, # 10 B, p. 1399 - 1401
  作者：Teetz、Geiger、Henning、Urbach

  DOI：——

  日期：——
• Stabilised Composition Comprising ACE Inhibitors
  申请人：Keramidas Panagiotis

  公开号：US20100035955A1

  公开（公告）日：2010-02-11

  A pharmaceutical composition comprising a) an ACE inhibitor prone to degradation or a pharmaceutically acceptable acid addition salt thereof; b) a stabilizing amount of an alkaline stabilizing agent; and c) pharmaceutically acceptable excipients wherein the composition further includes moisture controlling means.
• SOLID PHARMACEUTICAL FORMULATIONS OF RAMIPRIL AND AMLODIPINE BESYLATE, AND THEIR PREPARATION
  申请人：Khullar Praveen

  公开号：US20130146496A1

  公开（公告）日：2013-06-13

  The present invention is directed to solid stable pharmaceutical fixed dose compositions comprising ramipril, amlodipine besilate and pharmaceutically acceptable excipients, and to their preparation.