(2S,4R)-1-[(S)-2-((S)-1-Carboxy-3-phenyl-propylamino)-propionyl]-4-cyclohexyl-pyrrolidine-2-carboxylic acid | 83552-26-5

• 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: (2S,4R)-1-[(S)-2-((S)-1-Carboxy-3-phenyl-propylamino)-propionyl]-4-cyclohexyl-pyrrolidine-2-carboxylic acid
• 英文别名: (2S,4R)-1-[(2S)-2-[[(1S)-1-carboxy-3-phenylpropyl]amino]propanoyl]-4-cyclohexylpyrrolidine-2-carboxylic acid
• CAS: 83552-26-5
• 化学式: C₂₄H₃₄N₂O₅
• 分子量: 430.544
• InChiKey: XIDKYOYUSIBSHS-FIRPJDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 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：

  cis-4-cyclohexyl-L-proline hydrochloride 在 盐酸 、 sodium hydroxide 、 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 (2S,4R)-1-[(S)-2-((S)-1-Carboxy-3-phenyl-propylamino)-propionyl]-4-cyclohexyl-pyrrolidine-2-carboxylic acid
  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：EP0052991A1

  公开（公告）日：1982-06-02

  Carboxyalkyl dipeptides of the formula wherein R4 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.

  式中的羧烷基二肽 其中 R4 是 3-、4-、5- 或 4,4 取代的脯氨酸。这些化合物具有血管紧张素转换酶抑制活性，可用作降血压药。
• KRAPCHO, JOHN;TURK, CHESTER;CUSHMAN, DAVID W.;POWELL, JAMES R.;DEFORREST,+, J. MED. CHEM., 31,(1988) N 6, C. 1148-1160
  作者：KRAPCHO, JOHN、TURK, CHESTER、CUSHMAN, DAVID W.、POWELL, JAMES R.、DEFORREST,+

  DOI：——

  日期：——
• US4462943A
  申请人：——

  公开号：US4462943A

  公开（公告）日：1984-07-31