盐酸地拉普利杂质5 | 83398-08-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 中文名称: 盐酸地拉普利杂质5
• 英文名称: Delaprilat
• 英文别名: Delapril diacid；(2S)-2-[[(2S)-1-[carboxymethyl(2,3-dihydro-1H-inden-2-yl)amino]-1-oxopropan-2-yl]amino]-4-phenylbutanoic acid
• CAS: 83398-08-7
• 化学式: C₂₄H₂₈N₂O₅
• 分子量: 424.497
• InChiKey: PHASTBJLWIZXKB-KKSFZXQISA-N

物化性质

• 沸点：
  666.4±55.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  盐酸地拉普利 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以58%的产率得到盐酸地拉普利杂质5
  参考文献：
  名称：

  N- [N-[（S）-1-乙氧基羰基-3-苯基丙基] -L-丙氨酰] -N-（茚满-2-基）甘氨酸（CV-3317）的设计与合成酶抑制剂。

  摘要：

  一种新的血管紧张素转换酶（ACE）抑制剂N-[N-[(S)-1-乙氧基碳基-3-苯基丙基]-L-丙氨酸]-N-(茚-2-基)甘氨酸（9a）是在对ACE抑制剂中C端氨基酸部分的结构要求进行广泛研究后发现的。本文描述了9a的合成及其绝对构型的确定。

  DOI：

  10.1248/cpb.34.2852

文献信息

• Hydrolytic Profile for Ester- or Amide-linkage by Carboxylesterases pI 5.3 and 4.5 from Human Liver.
  作者：Satomi TAKAI、Ayuka MATSUDA、Yoshiko USAMI、Tetsuo ADACHI、Tadashi SUGIYAMA、Yoshihiro KATAGIRI、Masae TATEMATSU、Kazuyuki HIRANO

  DOI：10.1248/bpb.20.869

  日期：——

  Carboxylesterases (EC 3.1.1.1) from human liver were purified using Q-Sepharose, Sephadex G-150, isoelectrofocusing and Con A-Sepharose. The calculated molecular mass of the pI 5.3 enzyme was 120 kDa and 61 kDa from the results of Sephadex G-150 gel filtration and SDS-polyacrylamide gel electrophoresis (PAGE), respectively, suggesting that this enzyme is a dimer. On the other hand, carboxylesterase pI 4.5, with a molecular mass of 64 kDa, was a monomer. The activities of both enzymes were inhibited by typical serine enzyme inhibitors. Amino acid sequence analysis of the purified enzymes pI 5.3 and 4.5 showed high homology with rabbit carboxylesterase form 1 and 2, respectively. The results also suggested that carboxylesterase pI 5.3 is identical to the deduced amino acid sequence from cDNA for HU1, and that carboxylesterase pI 4.5 is identical to the deduced amino acid sequence from the cDNA registered as human carboxylesterase (hCE-2) in GenBank. We first purified carboxylesterase pI 4.5 and investigated its hydrolytic activity upon various drugs. The two enzymes differed in substrate specificity. Prodrugs of angiotensin-converting enzyme inhibitors, such as delapril and imidapril, were converted to active metabolites by carboxylesterase pI 5.3, but not by carboxylesterase pI 4.5. The hydrolysis velocity of temocapril by carboxylesterase pI 5.3 was 12-fold faster than by carboxylesterase pI 4.5. In contrast, aspirin, oxybutynin and procaine were hydrolyzed by only carboxylesterase pI 4.5. We also found that an amide-linkage in drugs, except for that in aniracetam, was not a good substrate for the two enzymes. Consequently, carboxylesterases pI 5.3 and 4.5 may be involved in the metabolism of various drugs containing an ester-linkage.

  人类肝脏中的羧酸酯酶（EC 3.1.1.1）通过Q-Sepharose、Sephadex G-150、等电聚焦和Con A-Sepharose进行纯化。pI 5.3酶的计算分子量为120 kDa，而通过Sephadex G-150凝胶滤过和SDS-聚丙烯酰胺凝胶电泳（PAGE）得到的结果分别为61 kDa，这表明该酶是二聚体。另一方面，pI 4.5的羧酸酯酶，分子量为64 kDa，是单体。这两种酶的活性均受到典型的丝氨酸酶抑制剂的抑制。纯化的pI 5.3和pI 4.5酶的氨基酸序列分析显示与兔羧酸酯酶1型和2型具有高度同源性。结果还表明，pI 5.3的羧酸酯酶与从cDNA中推导出的HU1的氨基酸序列相同，而pI 4.5的羧酸酯酶与在GenBank中注册的人类羧酸酯酶（hCE-2）的推导氨基酸序列相同。我们首先纯化了pI 4.5的羧酸酯酶，并研究了其对各种药物的水解活性。这两种酶在底物特异性上有所不同。血管紧张素转化酶抑制剂的前药，如德拉普利和伊米达普利，被pI 5.3羧酸酯酶转化为活性代谢物，而pI 4.5羧酸酯酶则无法转化。pI 5.3对肽环的水解速率是pI 4.5的12倍。相反，只有pI 4.5羧酸酯酶能水解阿司匹林、奥昔布宁和普鲁卡因。我们还发现，除阿尼拉西坦外，药物中的酰胺键对这两种酶并不是良好的底物。因此，pI 5.3和pI 4.5的羧酸酯酶可能参与水解含酯键的各种药物的代谢过程。
• Controlled release preparations
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0368247A2

  公开（公告）日：1990-05-16

  There is provided a matrix preparation produced by dispersing a pharmaceutically active ingredient into a matrix which is solid at ambient temperature and comprised of a fatty acid ester of a polyglycerol. The preparation has stable release-controlling ability, can be processed to fine granules, granules, capsules, tablets etc., and contributes to reduce the administration times of the active ingredient and side effects of the ingredient.

  本发明提供了一种基质制剂，其制备方法是将药物活性成分分散到基质中，该基质在环境温度下为固体，由聚甘油脂肪酸酯组成。 该制剂具有稳定的释放控制能力，可加工成细颗粒、颗粒剂、胶囊剂、片剂等，有助于减少活性成分的给药时间和副作用。
• Use of a selective inhibitor of neutral endopeptidase and an angiotensin converting enzyme inhibitor in the preparation of a pharmaceutical for treating congestive heart failure
  申请人：E.R. Squibb & Sons, Inc.

  公开号：EP0527624A2

  公开（公告）日：1993-02-17

  Congestive heart failure is treated by administration of a selective inhibitor of neutral endopeptidase and an angiotensin converting enzyme inhibitor. Captopril, fosinopril sodium, enalapril maleate and lisinopril are the preferred angiotensin converting enzyme inhibitors and the mercapto compounds of the formula are the preferred selective inhibitors of neutral endopeptidase.

  治疗充血性心力衰竭的方法是使用中性内肽酶选择性抑制剂和血管紧张素转换酶抑制剂。卡托普利、福辛普利钠、马来酸依那普利和赖欣普利是首选的血管紧张素转换酶抑制剂，巯基化合物的化学式为 是首选的中性内肽酶选择性抑制剂。
• OKA, YOSHIKAZU;NISHIKAWA, KOHEI;MIYAKE, AKIO
  作者：OKA, YOSHIKAZU、NISHIKAWA, KOHEI、MIYAKE, AKIO

  DOI：——

  日期：——
• ORAL SUSTAINED-RELEASE PREPARATION
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0800385A1

  公开（公告）日：1997-10-15