1,4-dithia-7-azaspiro<4.4>nonane-8-(S)-carboxylic acid methyl ester hydrochloride | 83552-42-5

• 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: 1,4-dithia-7-azaspiro<4.4>nonane-8-(S)-carboxylic acid methyl ester hydrochloride
• 英文别名: 1,4-dithia-7-diazaspiro<4.4>nonane-8-carboxylic acid methyl ester monohydrochloride；(S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid, methyl ester, hydrochloride；(S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid, methyl ester, monohydrochloride；methyl (8S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate;hydrochloride
• CAS: 83552-42-5
• 化学式: C₈H₁₃NO₂S₂*ClH
• 分子量: 255.79
• InChiKey: ZJXGFMIGXFLRCM-RGMNGODLSA-N

物化性质

• 熔点：
  137-138 °C

计算性质

• 辛醇/水分配系数(LogP)：
  1.12
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  88.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  (S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid, hydrochloride 在 氯化亚砜 作用下， 以 甲醇 为溶剂， 生成 1,4-dithia-7-azaspiro<4.4>nonane-8-(S)-carboxylic acid methyl ester hydrochloride
  参考文献：
  名称：

  Carboxyalkyl amino acid derivatives of various substituted prolines

  摘要：

  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。

  公开号：

  US04462943A1

文献信息

• Phosphonamidate compounds
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04432971A1

  公开（公告）日：1984-02-21

  Phosphonamidates of the formula ##STR1## wherein X is a substituted or unsubstituted imino or amino acid or ester. These compounds possess angiotensin converting enzyme activity and are thus useful as hypotensive agents.

  式中X为取代或未取代的亚胺基或氨基酸或酯。这些化合物具有血管紧张素转化酶活性，因此可用作降压剂。
• 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.
• (Phosphinyloxy)acyl amino acid inhibitors of angiotensin converting enzyme. 2. Terminal amino acid analogs of (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-proline
  作者：Donald S. Karanewsky、Michael C. Badia、David W. Cushman、Jack M. DeForrest、Tamara Dejneka、Ving G. Lee、Melanie J. Loots、Edward W. Petrillo

  DOI：10.1021/jm00167a028

  日期：1990.5

  Analogues of (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl)phosphinyl] oxy]-1-oxohexyl]-L-proline (1, SQ 29,852) in which the terminal proline residue has been replaced by a variety of substituted and heteroatom-substituted prolines, N-arylglycines, N-cycloalkylglycines, and bicyclic amino acids have been synthesized and evaluated as inhibitors of angiotensin converting enzyme in vitro and in vivo. In general, the addition of lipophilic substituents to the 4-position of proline of the parent phosphonate 1 resulted in substantial increases in in vitro activity. The largest improvements were observed in the case of cis-benzyl (36-fold) and dithioketal (24-fold) analogues 2r and 2x, respectively. These enhancements of in vitro activity were accompanied by modest increases (2-3.5-fold) in in vivo (iv) activity. Among the various terminal amino acid replacements examined in this study, the indoline-based analogue 2i was by far the most potent compound on iv administration in the normotensive rat.
• KARANEWSKY, DONALD S.;BADIA, MICHAEL C.;CUSHMAN, DAVID W.;DEFORREST, JACK+, J. MED. CHEM., 33,(1990) N, C. 1459-1469
  作者：KARANEWSKY, DONALD S.、BADIA, MICHAEL C.、CUSHMAN, DAVID W.、DEFORREST, JACK+

  DOI：——

  日期：——
• 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：——