[S-(R*,R*)]-Hexahydro-6-[[2-(acetylthio)-1-oxo-3-phenylpropyl]amino]-2,2-dimethyl-7-oxo-1H-azepine-1-acetic acid, ethyl ester | 160135-15-9

• 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-(R*,R*)]-Hexahydro-6-[[2-(acetylthio)-1-oxo-3-phenylpropyl]amino]-2,2-dimethyl-7-oxo-1H-azepine-1-acetic acid, ethyl ester
• 英文别名: ethyl 2-[(6S)-6-[[(2S)-2-acetylsulfanyl-3-phenylpropanoyl]amino]-2,2-dimethyl-7-oxoazepan-1-yl]acetate
• CAS: 160135-15-9
• 化学式: C₂₃H₃₂N₂O₅S
• 分子量: 448.583
• InChiKey: ADYAJTSESXVPES-OALUTQOASA-N

物化性质

• 沸点：
  645.4±55.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [S-(R*,R*)]-Hexahydro-6-[[2-(acetylthio)-1-oxo-3-phenylpropyl]amino]-2,2-dimethyl-7-oxo-1H-azepine-1-acetic acid, ethyl ester 在 sodium hydroxide 、 1,4-二巯基-2,3-丁二醇 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 4.58h， 以89%的产率得到[14C]-Gemopatrilat
  参考文献：
  名称：

  Deprotection and recrystallization processes

  摘要：

  酰巯基烷酰胺内酰胺酯或酸在碱性条件下，通过包含一种最小化二硫化物量的试剂来转化为相应的巯基烷酰胺内酰胺酯或酸。适当的试剂包括双硫醇、膦或亚膦还原剂、锌金属粉和氢亚硫酸钠。这些试剂也用于巯基烷酰胺内酰胺酸的再结晶和再加工。

  公开号：

  US06340752B1
• 作为产物：
  描述：

  (S)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-6-oxo-heptanoic acid benzyl ester 在 palladium on activated charcoal 叠氮基三甲基硅烷 、 三氟化硼乙醚 、 氢气 、 四氯化钛 、 1-羟基苯并三唑 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 234.0h， 生成 [S-(R*,R*)]-Hexahydro-6-[[2-(acetylthio)-1-oxo-3-phenylpropyl]amino]-2,2-dimethyl-7-oxo-1H-azepine-1-acetic acid, ethyl ester
  参考文献：
  名称：

  Vasopeptidase Inhibitors:  Incorporation of Geminal and Spirocyclic Substituted Azepinones in Mercaptoacyl Dipeptides

  摘要：

  A series of 7-(di)alkyl and spirocyclic substituted azepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. Clear structure-activity relationships with respect to both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) activity in vitro were observed. The best in this series, compound 1g, a geminally dimethylated C-7-substituted azepinone, demonstrated excellent blood pressure lowering in animal models. Compound 1g (BMS-189921) is characterized by a good duration of activity and excellent oral efficacy in models relevant to ACE or NEP inhibition, and its activity is comparable to that of the clinically efficacious agent omapatrilat. Consequently this inhibitor has been advanced clinically for the treatment of hypertension and congestive heart failure.

  DOI：

  10.1021/jm980542f

文献信息

• Vasopeptidase Inhibitors:  Incorporation of Geminal and Spirocyclic Substituted Azepinones in Mercaptoacyl Dipeptides
  作者：Jeffrey A. Robl、Richard Sulsky、Ellen Sieber-McMaster、Denis E. Ryono、Maria P. Cimarusti、Ligaya M. Simpkins、Donald S. Karanewsky、Sam Chao、Magdi M. Asaad、Andrea A. Seymour、Maxine Fox、Patricia L. Smith、Nick C. Trippodo

  DOI：10.1021/jm980542f

  日期：1999.1.1

  A series of 7-(di)alkyl and spirocyclic substituted azepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. Clear structure-activity relationships with respect to both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) activity in vitro were observed. The best in this series, compound 1g, a geminally dimethylated C-7-substituted azepinone, demonstrated excellent blood pressure lowering in animal models. Compound 1g (BMS-189921) is characterized by a good duration of activity and excellent oral efficacy in models relevant to ACE or NEP inhibition, and its activity is comparable to that of the clinically efficacious agent omapatrilat. Consequently this inhibitor has been advanced clinically for the treatment of hypertension and congestive heart failure.
• Deprotection and recrystallization processes
  申请人：Bristol-Myers Squibb Co.

  公开号：US06340752B1

  公开（公告）日：2002-01-22

  Acylmercaptoalkanoylamino lactam esters or acids are converted to the corresponding mercaptoalkanoylamino lactam ester or acid under basic conditions by including an agent which minimizes the amount of disulfides. Suitable agents are bismercaptans, phosphine or phosphite reducing agents, zinc metal powder, and sodium hydrosulfite. Such agents are also employed in the recrystallization and reprocessing of the mercaptoalkanoylamino lactam acids.

  酰巯基烷酰胺内酰胺酯或酸在碱性条件下，通过包含一种最小化二硫化物量的试剂来转化为相应的巯基烷酰胺内酰胺酯或酸。适当的试剂包括双硫醇、膦或亚膦还原剂、锌金属粉和氢亚硫酸钠。这些试剂也用于巯基烷酰胺内酰胺酸的再结晶和再加工。