H-histidine amide of (1'R,2'S,5S)-5-(2'-amino-3'-cyclohexyl-1'-hydroxypropyl)-3-ethyloxazolidin-2-one | 143127-85-9

• 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: H-histidine amide of (1'R,2'S,5S)-5-(2'-amino-3'-cyclohexyl-1'-hydroxypropyl)-3-ethyloxazolidin-2-one
• 英文别名: (2S)-2-amino-N-[(1R,2S)-3-cyclohexyl-1-[(5S)-3-ethyl-2-oxo-1,3-oxazolidin-5-yl]-1-hydroxypropan-2-yl]-3-(1H-imidazol-5-yl)propanamide
• CAS: 143127-85-9
• 化学式: C₂₀H₃₃N₅O₄
• 分子量: 407.513
• InChiKey: FYYKFPRIIWPUAX-XLAORIBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  H-histidine amide of (1'R,2'S,5S)-5-(2'-amino-3'-cyclohexyl-1'-hydroxypropyl)-3-ethyloxazolidin-2-one 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 -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：

  在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 H-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：

  Water-soluble renin inhibitors: design of a subnanomolar inhibitor with a prolonged duration of action

  摘要：

  Incorporation of nonreactive polar functionalities at the C- and N-termini of renin inhibitors led to the development of a subnanomolar compound (21) with millimolar solubility. This inhibitor demonstrated excellent efficacy and a long duration of action upon intravenous administration to monkeys. While activity was also observed intraduodenally, a comparison of the blood pressure responses indicated low bioavailability. Subsequent experiments in rats showed that, although the compound was absorbed from the gastrointestinal tract, extensive liver extraction severely limited bioavailability.

  DOI：

  10.1021/jm00169a024

文献信息

• Water-soluble renin inhibitors: design of a subnanomolar inhibitor with a prolonged duration of action
  作者：Saul H. Rosenberg、Keith W. Woods、Hing L. Sham、Hollis D. Kleinert、Donald L. Martin、Herman Stein、Jerome Cohen、David A. Egan、Barbara Bopp

  DOI：10.1021/jm00169a024

  日期：1990.7

  Incorporation of nonreactive polar functionalities at the C- and N-termini of renin inhibitors led to the development of a subnanomolar compound (21) with millimolar solubility. This inhibitor demonstrated excellent efficacy and a long duration of action upon intravenous administration to monkeys. While activity was also observed intraduodenally, a comparison of the blood pressure responses indicated low bioavailability. Subsequent experiments in rats showed that, although the compound was absorbed from the gastrointestinal tract, extensive liver extraction severely limited bioavailability.
• Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides
  作者：Saul H. Rosenberg、Kenneth P. Spina、Keith W. Woods、Jim Polakowski、Donald L. Martin、Zhengli Yao、Herman H. Stein、Jerome Cohen、Jennifer L. Barlow

  DOI：10.1021/jm00056a005

  日期：1993.2

  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.