1-[N-(1-(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl]-4-(S)-(phenylthio)-L-proline | 83551-92-2

• 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
• 英文名称: 1-[N-(1-(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl]-4-(S)-(phenylthio)-L-proline
• 英文别名: (2S,4S)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-4-phenylsulfanylpyrrolidine-2-carboxylic acid
• CAS: 83551-92-2
• 化学式: C₂₆H₃₂N₂O₅S
• 分子量: 484.616
• InChiKey: QQLGVUZZXZNJFA-QGQQZZQASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[N-(1-(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl]-4-(S)-(phenylthio)-L-proline 生成 (2S,4S)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-4-phenylsulfanylpyrrolidine-2-carboxylic acid;hydrochloride
  参考文献：
  名称：

  KRAPCHO, JOHN;TURK, CHESTER;CUSHMAN, DAVID W.;POWELL, JAMES R.;DEFORREST,+, J. MED. CHEM., 31,(1988) N 6, C. 1148-1160

  摘要：

  DOI：
• 作为产物：
  描述：

  顺式-4-苯基硫代-L-脯氨酸 (佐芬普利中间体) 在 4-二甲氨基吡啶 、 四丁基氟化铵 、 对甲苯磺酸 、 1-羟基苯并三唑一水物 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 63.25h， 生成 1-[N-(1-(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl]-4-(S)-(phenylthio)-L-proline
  参考文献：
  名称：

  Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines

  摘要：

  Analogues of captopril, enalaprilat, and the phosphinic acid [hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline incorporating 4-substituted proline derivatives have been synthesized and evaluated as inhibitors of angiotensin-converting enzyme (ACE) in vitro and in vivo. The 4-substituted prolines, incorporating alkyl, aryl, alkoxy, aryloxy, alkylthio, and arylthio substituents were prepared from derivatives of 4-hydroxy- and 4-ketoproline. In general, analogues of all three classes of inhibitors with hydrophobic substituents on proline were more potent in vitro than the corresponding unsubstituted proline compounds. 4-Substituted analogues of captopril showed greater potency and duration of action than the parent compound as inhibitors of the angiotensin I induced pressor response in normotensive rats. The S-benzoyl derivative of cis-4-(phenylthio)captopril, zofenopril, was found to be one of the most potent compounds of this class and is now being evaluated clinically as an antihypertensive agent. In the phosphinic acid series, the 4-ethylenethioketal and trans-4-cyclohexyl derivatives were found to be the most potent compounds in vitro and in vivo. A prodrug of the latter compound, fosinopril, is also being evaluated in clinical trials.

  DOI：

  10.1021/jm00401a014

文献信息

• Carboxyalkyl amino acid derivatives of various substituted prolines
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04462943A1

  公开（公告）日：1984-07-31

  Carboxyalkyl dipeptides of the formula ##STR1## wherein R.sub.4 is a 3-, 4-, 5-, or 4,4-substituted proline are disclosed. These compounds are useful as hypotensive agents due to their angiotensin converting enzyme inhibition activity.

  公开了化学式为##STR1##的羧基烷基二肽，其中R.sub.4是3-、4-、5-或4,4-取代的脯氨酸。这些化合物由于其抑制血管紧张素转化酶活性而可用作降压药物。
• US4462943A
  申请人：——

  公开号：US4462943A

  公开（公告）日：1984-07-31