(2S)-2-[[(2S)-1-[(2S)-2-甲基-3-巯基丙酰]吡咯烷-2-羰基]氨基]-3-苯丙酸 | 74259-08-8

• 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: (2S)-2-[[(2S)-1-[(2S)-2-甲基-3-巯基丙酰]吡咯烷-2-羰基]氨基]-3-苯丙酸
• 中文别名: 3-(9,10-二羟基-7-甲氧基-3-甲基-1-羰基-3,4-二氢-1H-苯并[g]异色烯-8-基)-5-羟基-2-甲氧基萘-1,4-二酮
• 英文名称: 1-((S)-3-mercapto-2-methylpropanoyl)-L-prolyl-L-phenylalanine
• 英文别名: desacetyl-alacepril；desacetylalacepril；deacetylalacepril；(2S)-2-[[(2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid
• CAS: 74259-08-8
• 化学式: C₁₈H₂₄N₂O₄S
• 分子量: 364.466
• InChiKey: GICPPYOSOHKZPY-SNPRPXQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  阿拉普利 在 ammonium hydroxide 作用下， 反应 2.0h， 以59%的产率得到(2S)-2-[[(2S)-1-[(2S)-2-甲基-3-巯基丙酰]吡咯烷-2-羰基]氨基]-3-苯丙酸
  参考文献：
  名称：

  Synthesis of 1-((S)-3-acetylthio-2-methylpropanoyl)-L-propyl-L-phenylalanine (alacepril) and one of its active metabolites, the desacetyl derivative (DU-1227).

  摘要：

  报道了临床使用的抗高血压药物1-((S)-3-乙酰巯基-2-甲基丙酰基)-L-脯氨酰-L-苯丙氨酸1（阿拉普利，代码名：DU-1219）及其活性代谢物之一1-((S)-3-巯基-2-甲基丙酰基)-L-脯氨酰-L-苯丙氨酸2（代码名：DU-1227）的合成。还描述了氯醛在L-脯氨酸N-甲酰化中的应用。根据1及其乙酯4的光谱检查结果，推测溶液中1的反式构象分子内存在氢键。

  DOI：

  10.1248/cpb.38.529

文献信息

• Effect of peptide-based captopril analogues on angiotensin converting enzyme activity and peroxynitrite-mediated tyrosine nitration
  作者：Bhaskar J. Bhuyan、Govindasamy Mugesh

  DOI：10.1039/c1ob05148b

  日期：——

  Angiotensin converting enzyme (ACE) regulates the blood pressure by converting angiotensin I to angiotensin II and bradykinin to bradykinin 1–7. These two reactions elevate the blood pressure as angiotensin II and bradykinin are vasoconstrictory and vasodilatory hormones, respectively. Therefore, inhibition of ACE is an important strategy for the treatment of hypertension. The natural substrates of

  血管紧张素 转换酶（ACE）通过转换来调节血压 血管紧张素 我来 血管紧张素II 和 缓激肽 到 缓激肽1–7。这两个反应使血压升高血管紧张素II 和 缓激肽分别是血管收缩激素和血管舒张激素。因此，抑制ACE是治疗高血压的重要策略。ACE的天然底物，即，血管紧张素II 和 缓激肽在水解位点附近含有Pro-Phe基序。因此，在ACE的活性位点可能存在Pro-Phe结合口袋，这可能有助于底物结合。有鉴于此，我们合成了一系列含巯基和硒醇的二肽和卡托普利类似物并研究了它们的ACE抑制活性。这项研究表明硒醇或巯基部分和脯氨酸残基对于ACE抑制都是必不可少的。虽然引入了苯丙氨酸残基卡托普利 并且它的硒类似物大大降低了抑制作用，在ACE的活性位点似乎有一个Phe结合口袋。
• 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。
• ——
  作者：Shigeyuki Usui、Masafumi Kubota、Kazuhiro Iguchi、Tadashi Kiho、Tadashi Sugiyama、Yoshihiro Katagiri、Kazuyuki Hirano

  DOI：10.1023/a:1025073720126

  日期：——

  Purpose. In this work, the alacepril thiolesterase, which catalyzes the hydrolyzing reaction of the thiolester linkage in alacepril and the conversion from alacepril to deacetylalacepril, was purified from rat liver cytosol and characterized.Methods. A purification procedure for the thiolesterase consisted of ammonium sulfate fractionation and chromatographies with phenyl Sepharose CL-4B, Q Sepharose FF, ceramic hydroxylapatite, and phenyl Sepharose HP. The thiolesterase activity was assayed for alacepril as a substrate and the reaction product, deacetylalacepril, was measured using high-performance liquid chromatography.Results. The purified thiolesterase is heterodimeric with a molecular mass of 29 and 36 kDa subunits as estimated by sodium dodecyl sulfate -polyacrylamide gel electrophoresis. N-terminal amino acid sequence of these subunits reveals that the thiolesterase is identical to sialic acid 9-O-acetylesterase. The thiolesterase hydrolyzes not only the thiolester bond in alacepril, spironolactone, and acetyl coenzyme A but also the carboxylester bond in alpha-naphtyl acetate. The alacepril thiolestrase activity is competitively inhibited by alpha-naphtyl acetate.Conclusion. The thiolesterase, i.e., sialic acid 9-O-acetylesterase, seems to be involved in the metabolism of certain drugs such as alacepril and spironolactone. However, drugs having ester-type and amide-type linkages, for example dilazep, aniracetam, and benazepril, are not substrates for the thiolestrase.
• SAWAYAMA, TADAHIRO;ITOKAWA, AKIRA;SHIMADA, KANJI;DOI, YASUMASA;KIMURA, YO+, CHEM. AND PHARM. BULL., 38,(1990) N, C. 529-531
  作者：SAWAYAMA, TADAHIRO、ITOKAWA, AKIRA、SHIMADA, KANJI、DOI, YASUMASA、KIMURA, YO+

  DOI：——

  日期：——
• KAGEMOTO, AKIRA;NAKAO, MASASHI;NEGORO, TOSHIYUKI;SEKINE, YUTAKA;HASHIMOTO+, RADIOISOTOPES, 1985, 34, N 8, 408-413
  作者：KAGEMOTO, AKIRA、NAKAO, MASASHI、NEGORO, TOSHIYUKI、SEKINE, YUTAKA、HASHIMOTO+

  DOI：——

  日期：——