(S)-2-phthalimido-6-methyl-6-azidoheptanoic acid, phenylmethyl ester | 197902-93-5

• 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: (S)-2-phthalimido-6-methyl-6-azidoheptanoic acid, phenylmethyl ester
• 英文别名: benzyl (2S)-6-azido-2-(1,3-dioxoisoindol-2-yl)-6-methylheptanoate
• CAS: 197902-93-5
• 化学式: C₂₃H₂₄N₄O₄
• 分子量: 420.468
• InChiKey: UATCKMMYAKQKSP-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-phthalimido-6-methyl-6-azidoheptanoic acid, phenylmethyl ester 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 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 115.5h， 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：

  benzyl (S)-2-(1,3-dioxoisoindolin-2-yl)-6-oxohexanoate 在 草酰氯 、 叠氮基三甲基硅烷 、 三氟化硼乙醚 、 四氯化钛 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 124.75h， 生成 (S)-2-phthalimido-6-methyl-6-azidoheptanoic acid, phenylmethyl 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

• N-formyl hydroxylamine containing compounds useful as ACE inhibitors and/or NEP inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：US06777550B1

  公开（公告）日：2004-08-17

  N-formyl hydroxylamines are provided which have the structure wherein R is H, alkyl, alkenyl, aryl-(CH2)p—, heteroaryl-(CH2)p— or cycloheteroalkyl-(CH2)p— R1 is H or COR2 where R2 is alkyl, aryl-(CH2)p—, cycloheteroalkyl-(CH2)p—, heteroaryl-(CH2)p—, alkoxy or cycloalkyl-(CH2)p—, p is 0 to 8, and A is a dipeptide derived from an amino acid or is a conformationally restricted dipeptide mimic. The above compounds are useful in treating hypertension congestive heart failure, renal failure, and hepatic cirrhosis.

  提供了具有以下结构的N-甲酰羟胺，其中R为H，烷基，烯基，芳基-(CH2)p—，杂芳基-(CH2)p—或环杂芳基-(CH2)p—；R1为H或COR2，其中R2为烷基，芳基-(CH2)p—，环杂芳基-(CH2)p—，杂芳基-(CH2)p—，烷氧基或环烷基-(CH2)p—；p为0至8，A为来源于氨基酸的二肽或是具有构象限制的二肽模拟物。上述化合物在治疗高血压、充血性心力衰竭、肾功能衰竭和肝硬化方面具有用途。
• 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.