(S)-Hexahydro-6-[(triphenylmethyl)amino]-2,2-dimethyl-7-oxo-1H-azepine-1-acetic acid, ethyl ester | 182886-84-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (S)-Hexahydro-6-[(triphenylmethyl)amino]-2,2-dimethyl-7-oxo-1H-azepine-1-acetic acid, ethyl ester
• 英文别名: ethyl 2-[(6S)-2,2-dimethyl-7-oxo-6-(tritylamino)azepan-1-yl]acetate
• CAS: 182886-84-6
• 化学式: C₃₁H₃₆N₂O₃
• 分子量: 484.638
• InChiKey: SBSZUWUDLIKWHT-MHZLTWQESA-N

物化性质

• 沸点：
  618.2±55.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-Hexahydro-6-[(triphenylmethyl)amino]-2,2-dimethyl-7-oxo-1H-azepine-1-acetic acid, ethyl ester 在 sodium hydroxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 8.5h， 生成 [14C]-Gemopatrilat
  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
• 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 、 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 231.0h， 生成 (S)-Hexahydro-6-[(triphenylmethyl)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.