(2R,3aR,6aR)-雷米普利 | 129939-63-5

• 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: (2R,3aR,6aR)-雷米普利
• 中文别名: 雷米普利杂质N
• 英文名称: ramipril
• 英文别名: 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-(S)-alanyl]-(1R,3R,5R)-2-azabicyclo[3.3.0]octane-3-carboxylic acid；(2R,3aR,6aR)-1-((2S)-2-(((1S)-1-(Ethoxycarbonyl)-3-phenylpropyl)amino)propanoyl)octahydrocyclopenta(b)pyrrole-2-carboxylic acid；(2R,3aR,6aR)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrole-2-carboxylic acid
• CAS: 129939-63-5
• 化学式: C₂₃H₃₂N₂O₅
• 分子量: 416.517
• InChiKey: HDACQVRGBOVJII-ABHMUUKNSA-N

物化性质

• 熔点：
  40 - 50°C
• 溶解度：
  可溶于乙腈（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,3aR,6aR)-雷米普利 、 在 NaOH 作用下， 以 水 为溶剂， 生成 [Zn0.68Al0.32(OH)2](ramipril(-1H))0.219(CO3)0.051*0.65H2O
  参考文献：
  名称：

  Layered double hydroxides as supports for intercalation and sustained release of antihypertensive drugs

  摘要：

  Zn/Al layered double hydroxides (LDHs) were intercalated with the anionic antihypertensive drugs Enalpril, Lisinopril, Captopril and Ramipril by using coprecipitation or ion-exchange technique/ TG-MS analyses suggested that the thermal stability of Ena(-), Lis(-) (arranged with monolayer, resulted from X-ray diffraction (XRD) and Fourier transform infrared spectra (FT-IR) analysis was enhanced much more than Cap- and Ram- (arranged with bilayer). The release studies show that the release rate of all samples markedly decreased in both pH 4.25 and 7.45. However, the release time of Ena-, Lis- were much longer compared with Cap-, Ram- in both pH 4.25 and 7.45, it is possible that the intercalated guests, arranged with monolayer in the interlayer, show lesser repulsive force and strong affinity with the LDH layers. And the release data followed both the Higuchi-square-root law and the first-order equation well. Based on the analysis of batch releasse, intercalated structural models as well as the TG-DTA results, we conclude that for drug-LDH, stronger the affinity between intercalated anions and the layers is, better the thermal property and the stability to the acid attack of drug-LDH, and the intercalated anions are easier apt to monolayer arrangement within the interlayer, were presented. (c) 2008 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jssc.2008.06.009
• 作为产物：
  描述：

  (E)-(-)-八氢环戊二烯并[b]吡咯-2-甲酸盐酸盐 、 N-[1-(S)-乙氧羰基-3-苄丙基]-L-丙氨酸-N-羰甲醛 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (2R,3aR,6aR)-雷米普利 、 雷米普利
  参考文献：
  名称：

  [EN] A PROCESS FOR THE PREPARATION OF 2-[N-­ [(S)-1-ETHOXYCARBONYL-3-PHENYLPROPYL]-(S)-ALANYL]-(1S, 3S, 5S) -2-AZABICYCLO [3.3.0] OCTANE-3­-CARBOXYLIC ACID
  [FR] PROCEDE DE PREPARATION D'ACIDE 2-[N-[(S)-1-ETHOXYCARBONYL-3-PHENYLPROPYL]-(S)-ALANYL]-(1S, 3S, 5S)-2-AZABICYCLO[3.3.0] OCTANE-3-CARBOXYLIQUE

  摘要：

  一种制备2-[N-[(S)-1-乙氧羰基-3-苯丙基]-(S)-丙氨酸]-(1S,3S,5S)-2-氮杂双环[3.3.0]辛烷-3-羧酸，即雷米普利的方法涉及将2-[N-[(S)-1-乙氧羰基-3-苯丙基]-(S)-丙氨酸的活化衍生物与混合(1R*、3R*、5R*)-2-氮杂双环[3.3.0]辛烷-3-羧酸进行缩合反应，然后通过用溶剂处理，从得到的2-[N-[(S)-1-乙氧羰基-3-苯丙基]-(S)-丙氨酸]-(1S,3S,5S)-2-氮杂双环[3.3.0]辛烷-3-羧酸的二对映异构体混合物中分离所需的对映异构体(1a)，即将其与选择性溶解非期望的对映异构体(1b)的溶剂处理，而对映异构体(1a)保持未溶解。

  公开号：

  WO2005108366A1

文献信息

• 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。
• Association entre un anti-athérothrombotique et un inhibiteur de l'enzyme de conversion de l'angiotensine
  申请人：Les Laboratoires Servier

  公开号：EP2036886A1

  公开（公告）日：2009-03-18

  Association d'un anti-athérothrombotique et d'un inhibiteur de l'enzyme de conversion de l'angiotensine (IECA), ainsi que les compositions pharmaceutiques qui les contiennent.

  一种抗动脉粥样硬化血栓形成药和一种血管紧张素转换酶（ACE）抑制剂的复方制剂，以及含有它们的药物组合物。
• EP2598479B1
  申请人：——

  公开号：EP2598479B1

  公开（公告）日：2015-04-01
• Process for Crystallization of Ramipril and Preparation of a Hydrated Form Thereof
  申请人：Singh Girij Pal

  公开号：US20080171780A1

  公开（公告）日：2008-07-17

  The present invention relates to a novel method for obtaining (2S,3aS,6aS)-1-[(S)-2-[[(S)-1-(ethoxycarbonyl)-3-phenylpropyl]-amino]propanoyl]octahydro cyclopenta[b]pyrrole-2-carboxylic acid, viz. Ramipril(I) in high optical purity, free of other stereoisomers, and in high bulk density. The present invention also relates to a novel hydrated form of Ramipril(I) and a process for preparation thereof.
• Process for the Preparation of 2-[N-[{S)-1-Ethoxycarbonyl-3-Phenylpropyl]-(S)-Alanyl]-(1S,3S,5S)-2-Azabicyclo[3.3.0]Oct- an-3-Carboxylic Acid
  申请人：Bankowski Krzysztof

  公开号：US20080234493A1

  公开（公告）日：2008-09-25

  A process for preparation of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-(S)-alanyl]-(1S,3S,5S)-2- azabicyclo [3.3.0] octane-3-carboxylic acid, ie. Ramipril, involves condensation of an activated derivative of 2-[N-](S)-1-ethoxycarbonyl-3-phenylpropyl]-(S)-alanine with racemic (1R*,3R*,5R*)-2-azabicyclo[3.3.0]octane-3-carboxylic acid, and then the desired diastereoisomer (1a) is separated from the obtained diastereoisomeric mixture of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl](S)-alanyl]-(1S,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (1a) and 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl -alanyl]-(1R,3R,5R)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (1b) by treating it with a solvent that selectively dissolves the undesired diastereoisomer (1b) while the diastereoisomer (1a) remains undissolved.