(S)-7-[[Hydroxy(4-phenylbutyl)phosphinyl)acetyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid | 83623-49-8

• 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: (S)-7-[[Hydroxy(4-phenylbutyl)phosphinyl)acetyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid
• 英文别名: (8S)-7-[2-[hydroxy(4-phenylbutyl)phosphoryl]acetyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid
• CAS: 83623-49-8
• 化学式: C₁₉H₂₆NO₅PS₂
• 分子量: 443.525
• InChiKey: SCLVAMUVMTZGEU-INIZCTEOSA-N

物化性质

• 熔点：
  118-120 °C
• 沸点：
  797.6±60.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-7-[[Hydroxy(4-phenylbutyl)phosphinyl)acetyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid 生成 dilithium;(8S)-7-[2-[oxido(4-phenylbutyl)phosphoryl]acetyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate
  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：

  1,4-dithia-7-azaspiro<4.4>nonane-8-(S)-carboxylic acid methyl ester hydrochloride 在 sodium hydroxide 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 16.5h， 生成 (S)-7-[[Hydroxy(4-phenylbutyl)phosphinyl)acetyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-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

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

  公开号：US04337201A1

  公开（公告）日：1982-06-29

  Esters of phosphinylalkanoyl prolines and phosphinylalkanoyl substituted prolines are inhibitors of angiotensin converting enzyme and are useful in the treatment of hypertension.

  磷酰基丙氨酰脯氨酸酯和磷酰基丙氨酰取代脯氨酸酯是抑制血管紧张素转化酶的抑制剂，并且在治疗高血压方面具有用处。
• Esters of phosphinylalkanoyl substituted prolines
  申请人：E.R. Squibb & Sons, Inc.

  公开号：EP0097050A1

  公开（公告）日：1983-12-28

  Hypotensive activity is exhibited by new compounds having the formula and salts thereof wherein R1 is alkyl, aryl, arylalkyl, cycloalkyl, or cycloalkylalkyl; R2 is cycloalkyl, 3-cyclohexenyl or 2-alkyl-3-cyclohexenyl; R3 is alkyl, cycloalkyl or phenyl; R4 is hydrogen or alkyl; one of R5 and R6 is hydrogen and the other is alkyl-X-, phenyl-X-, alkoxy, phenyloxy, phenyl, cycloalkyl, alkyl, or phenylalkyl; or together R5 and R6 are -XCH2CH2X-; and X is R7 is hydrogen or and n is 0 or 1.

  具有式及其盐的新化合物具有降血压活性，其中 R1 是烷基、芳基、芳烷基、环烷基或环烷基烷基；R2 是环烷基、3-环己烯基或 2-烷基-3-环己烯基；R3 是烷基、环烷基或苯基；R4 是氢或烷基；R5 和 R6 中的一个是氢，另一个是烷基-X-、苯基-X-、烷氧基、苯氧基、苯基、环烷基、烷基或苯基烷基；或者 R5 和 R6 一起是-XCH2CH2X-；X 是 R7 是氢或 n 是 0 或 1。
• 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：——
• US4337201A
  申请人：——

  公开号：US4337201A

  公开（公告）日：1982-06-29
• US4384123A
  申请人：——

  公开号：US4384123A

  公开（公告）日：1983-05-17