7-(3-mercapto-2-(S)-methylpropanoyl)-1,4-dithia-7-azaspiro<4.4>nonane-8(S)-carboxylic acid | 75776-82-8

• 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
• 英文名称: 7-(3-mercapto-2-(S)-methylpropanoyl)-1,4-dithia-7-azaspiro<4.4>nonane-8(S)-carboxylic acid
• 英文别名: 7-(3-mercapto-2-(S)-methylpropanoyl)-1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxylic acid；(8S)-7-[(2S)-2-methyl-3-sulfanylpropanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid
• CAS: 75776-82-8
• 化学式: C₁₁H₁₇NO₃S₃
• 分子量: 307.459
• InChiKey: SWKDKPVRLQUCEM-SFYZADRCSA-N

物化性质

• 熔点：
  116-118 °C
• 沸点：
  564.0±50.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1,4-dithia-7-azaspiro<4.4>nonane-8-(S)-carboxylic acid methyl ester hydrochloride 在 sodium hydroxide 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 1-羟基苯并三唑一水物 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 76.0h， 生成 7-(3-mercapto-2-(S)-methylpropanoyl)-1,4-dithia-7-azaspiro<4.4>nonane-8(S)-carboxylic acid
  参考文献：
  名称：

  Synthesis and pharmacological activity of angiotensin-converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines

  摘要：

  The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.

  DOI：

  10.1021/jm00399a033

文献信息

• Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines
  作者：John Krapcho、Chester Turk、David W. Cushman、James R. Powell、Jack M. DeForrest、Ervin R. Spitzmiller、Donald S. Karanewsky、Mark Duggan、George Rovnyak

  DOI：10.1021/jm00401a014

  日期：1988.6

  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.
• SMITH, ELIZABETH M.;SWISS, GERALD F.;NEUSTADT, BERNARD R.;GOLD, ELIJAH H.+, J. MED. CHEM., 31,(1988) N 4, 875-885
  作者：SMITH, ELIZABETH M.、SWISS, GERALD F.、NEUSTADT, BERNARD R.、GOLD, ELIJAH H.+

  DOI：——

  日期：——
• 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：——
• Synthesis and pharmacological activity of angiotensin-converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines
  作者：Elizabeth M. Smith、Gerald F. Swiss、Bernard R. Neustadt、Elijah H. Gold、Jane A. Sommer、Arthur D. Brown、Peter J. S. Chiu、Rosa Moran、Edmund J. Sybertz、Thomas Baum

  DOI：10.1021/jm00399a033

  日期：1988.4

  The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.