(2S,4S,5S)-1-<3-(tert-butyloxycarbonyl)-2,2-dimethyl-4-(cyclohexylmethyl)-5-oxazolidinyl>-2-(pentanoylamino)-3-methylbutane | 130317-36-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2S,4S,5S)-1-<3-(tert-butyloxycarbonyl)-2,2-dimethyl-4-(cyclohexylmethyl)-5-oxazolidinyl>-2-(pentanoylamino)-3-methylbutane
• 英文别名: tert-butyl (4S,5S)-4-(cyclohexylmethyl)-2,2-dimethyl-5-[(2S)-3-methyl-2-(pentanoylamino)butyl]-1,3-oxazolidine-3-carboxylate
• CAS: 130317-36-1
• 化学式: C₂₇H₅₀N₂O₄
• 分子量: 466.705
• InChiKey: XYDYXUXXMXZROJ-VABKMULXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.42
• 重原子数：
  33.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  67.87
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2S,4S,5S)-1-<3-(tert-butyloxycarbonyl)-2,2-dimethyl-4-(cyclohexylmethyl)-5-oxazolidinyl>-2-(pentanoylamino)-3-methylbutane 在 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.5h， 生成 {(S)-1-[(S)-1-((1S,2S,4S)-1-Cyclohexylmethyl-2-hydroxy-5-methyl-4-pentanoylamino-hexylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester
  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：

  正丁基氯化镁 、 2-(S)-((3-(tert-butyloxycarbonyl)-2,2-dimethyl-4(S)-(cyclohexylmethyl)-5(S)-oxazolidinyl)methyl)-3-methylbutanoic acid 在 二苯基膦叠氮化物 、 三乙胺 作用下， 生成 (2S,4S,5S)-1-<3-(tert-butyloxycarbonyl)-2,2-dimethyl-4-(cyclohexylmethyl)-5-oxazolidinyl>-2-(pentanoylamino)-3-methylbutane
  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