顺式-4-环己基-L-脯氨酸 | 785001-74-3

• 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: 顺式-4-环己基-L-脯氨酸
• 英文名称: cis-4-cyclohexyl-L-proline
• 英文别名: (2S,4R)-4-cyclohexylpyrrolidin-1-ium-2-carboxylate
• CAS: 785001-74-3
• 化学式: C₁₁H₁₉NO₂
• 分子量: 197.277
• InChiKey: XRZWVSXEDRYQGC-UWVGGRQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  顺式-4-环己基-L-脯氨酸 在 三甲基溴硅烷 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 48.0h， 生成 (2S,4R)-4-Cyclohexyl-1-{2-[hydroxy-(4-phenyl-butyl)-phosphinoyl]-acetyl}-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
• 作为产物：
  描述：

  N-cbz-4-氧-L-脯氨酸 在 platinum(IV) oxide 、 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 三氟乙酸 为溶剂， 反应 36.0h， 生成 顺式-4-环己基-L-脯氨酸
  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。
• HIV protease inhibitors
  申请人：JAPAN ENERGY CORPORATION

  公开号：EP0490667A2

  公开（公告）日：1992-06-17

  Human immunodeficiency virus (HIV) protease inhibitors comprising a compound represented by the following general formula or pharmaceutically acceptable salt thereof: The inhibitors are effective for treating a patient suffering from AIDS and AIDS related diseases.

  人类免疫缺陷病毒（HIV）蛋白酶抑制剂，包括由以下通式代表的化合物或其药学上可接受的盐： 这些抑制剂可有效治疗艾滋病和艾滋病相关疾病患者。
• Non-canonical insulins and their uses
  申请人：California Institute of Technology

  公开号：US10640546B2

  公开（公告）日：2020-05-05

  In some aspects, the invention relates to an insulin derivative, comprising a cyclic amino acid at position B28 or B29, wherein the cyclic amino acid is not L-proline. In some aspects, the invention relates to a method of making said insulin derivative. In some aspects, the invention relates to a pharmaceutical composition comprising said insulin derivative. In some aspects the invention relates to a method of treating a disease or condition in a subject comprising administering to the subject a composition comprising said insulin derivative.

  在某些方面，本发明涉及一种胰岛素衍生物，其包含位于 B28 或 B29 位的环状氨基酸，其中环状氨基酸不是 L-脯氨酸。在某些方面，本发明涉及一种制造所述胰岛素衍生物的方法。在某些方面，本发明涉及一种包含所述胰岛素衍生物的药物组合物。在某些方面，本发明涉及一种治疗受试者疾病或状况的方法，该方法包括向受试者施用包含所述胰岛素衍生物的组合物。
• ——
  作者：THOTTATHIL J. K.

  DOI：——

  日期：——
• Phosphinylalkanoyl substituted prolines
  申请人：E.R. Squibb & Sons, Inc.

  公开号：EP0053902B1

  公开（公告）日：1985-04-03