tert-butyl (4S,5S)-4-(cyclohexylmethyl)-2,2-dimethyl-5-[(2S)-3-methyl-2-(4-methyl-1,4-diazepane-1-carbonyl)butyl]-1,3-oxazolidine-3-carboxylate | 140660-90-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧氮杂卓类
• 英文名称: tert-butyl (4S,5S)-4-(cyclohexylmethyl)-2,2-dimethyl-5-[(2S)-3-methyl-2-(4-methyl-1,4-diazepane-1-carbonyl)butyl]-1,3-oxazolidine-3-carboxylate
• CAS: 140660-90-8
• 化学式: C₂₉H₅₃N₃O₄
• 分子量: 507.758
• InChiKey: SFQNFPXHKPRBPH-SDHOMARFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.52
• 重原子数：
  36.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  62.32
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (4S,5S)-4-(cyclohexylmethyl)-2,2-dimethyl-5-[(2S)-3-methyl-2-(4-methyl-1,4-diazepane-1-carbonyl)butyl]-1,3-oxazolidine-3-carboxylate 在 三氟乙酸 作用下， 生成
  参考文献：
  名称：

  C-Terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties

  摘要：

  We describe the development of a series of soluble, potent, and bioavailable nonpeptide renin inhibitors. These inhibitors derived from a series of novel nonpeptide renin inhibitors which were recently identified in our laboratories, by alteration of the nature of the C-terminus (P2') of the molecules. Introduction of basic substituents into modified hydroxyethylene dipeptide isosteres gave inhibitors with improved solubility as well as improved potency against human plasma renin. In addition, these modifications produced inhibitors which displayed markedly improved intraduodenal bioavailability in both the ferret and cynomolgus monkey. We also present data which demonstrate excellent efficacy in the monkey for A-74273 (65), with an intraduodenal bioavailability of 16 +/- 4% in the monkey, compared to 1.7 +/- 0.5% for the dipeptide renin inhibitor enalkiren (A-64662, 75). A-74273 is an example of a nonpeptide inhibitor which possesses a good balance of the desirable properties of potency, solubility, and lipophilicity and which is well absorbed into the intestine.

  DOI：

  10.1021/jm00088a007
• 作为产物：
  描述：

  N-甲基高哌嗪 、 2-(S)-((3-(tert-butyloxycarbonyl)-2,2-dimethyl-4(S)-(cyclohexylmethyl)-5(S)-oxazolidinyl)methyl)-3-methylbutanoic acid 在 N-甲基吗啉 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 tert-butyl (4S,5S)-4-(cyclohexylmethyl)-2,2-dimethyl-5-[(2S)-3-methyl-2-(4-methyl-1,4-diazepane-1-carbonyl)butyl]-1,3-oxazolidine-3-carboxylate
  参考文献：
  名称：

  C-Terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties

  摘要：

  We describe the development of a series of soluble, potent, and bioavailable nonpeptide renin inhibitors. These inhibitors derived from a series of novel nonpeptide renin inhibitors which were recently identified in our laboratories, by alteration of the nature of the C-terminus (P2') of the molecules. Introduction of basic substituents into modified hydroxyethylene dipeptide isosteres gave inhibitors with improved solubility as well as improved potency against human plasma renin. In addition, these modifications produced inhibitors which displayed markedly improved intraduodenal bioavailability in both the ferret and cynomolgus monkey. We also present data which demonstrate excellent efficacy in the monkey for A-74273 (65), with an intraduodenal bioavailability of 16 +/- 4% in the monkey, compared to 1.7 +/- 0.5% for the dipeptide renin inhibitor enalkiren (A-64662, 75). A-74273 is an example of a nonpeptide inhibitor which possesses a good balance of the desirable properties of potency, solubility, and lipophilicity and which is well absorbed into the intestine.

  DOI：

  10.1021/jm00088a007