-3,3-dimethylpropionyl>-O-methyltyrosinyl>-L-histidine amide of (1'R,2'S,5S)-5-<2'-amino-3'cyclohexyl-1'-hydroxypropyl>-3-ethyloxazolidin-2-one | 1054759-30-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: -3,3-dimethylpropionyl>-O-methyltyrosinyl>-L-histidine amide of (1'R,2'S,5S)-5-<2'-amino-3'cyclohexyl-1'-hydroxypropyl>-3-ethyloxazolidin-2-one
• 英文别名: benzyl N-[4-[[(2S)-1-[[(2S)-1-[[(1R,2S)-3-cyclohexyl-1-[(5S)-3-ethyl-2-oxo-1,3-oxazolidin-5-yl]-1-hydroxypropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-2-methyl-4-oxobutan-2-yl]carbamate
• CAS: 1054759-30-6
• 化学式: C₄₃H₅₉N₇O₉
• 分子量: 817.983
• InChiKey: HIOZOHDIRIOCSA-NFXBYIOWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  59
• 可旋转键数：
  21
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  213
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  溶剂黄146 、 -3,3-dimethylpropionyl>-O-methyltyrosinyl>-L-histidine amide of (1'R,2'S,5S)-5-<2'-amino-3'cyclohexyl-1'-hydroxypropyl>-3-ethyloxazolidin-2-one 在 palladium on activated charcoal 氢气 作用下， 反应 2.5h， 以90%的产率得到-L-histidine amide of (1'R,2'S,5S)-5-<2'-amino-3'cyclohexyl-1'-hydroxypropyl>-3-ethyloxazolidin-2-one bisacetic acid
  参考文献：
  名称：

  Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides

  摘要：

  A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors. Optimum structures, exemplified by 25 and 41, incorporated a single, solubilizing substituent at the C- or N-terminus combined with a lipophilic P2-site residue. Both inhibitors gave unprecedented plasma drug levels upon intraduodenal administration to monkeys, and the calculated bioavailability for 41 (14 +/- 4%) is the highest reported for any peptidic renin inhibitor.

  DOI：

  10.1021/jm00056a005
• 作为产物：
  描述：

  2-氨基-3-(4-甲氧基苯基)丙酸甲酯 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 lithium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 -3,3-dimethylpropionyl>-O-methyltyrosinyl>-L-histidine amide of (1'R,2'S,5S)-5-<2'-amino-3'cyclohexyl-1'-hydroxypropyl>-3-ethyloxazolidin-2-one
  参考文献：
  名称：

  Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides

  摘要：

  A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors. Optimum structures, exemplified by 25 and 41, incorporated a single, solubilizing substituent at the C- or N-terminus combined with a lipophilic P2-site residue. Both inhibitors gave unprecedented plasma drug levels upon intraduodenal administration to monkeys, and the calculated bioavailability for 41 (14 +/- 4%) is the highest reported for any peptidic renin inhibitor.

  DOI：

  10.1021/jm00056a005