(2R,3S)-dimethyl <3-<<<(tert-butyloxycarbonyl)phenylalaninyl>histidyl>amino>-4-cyclohexyl-2-hydroxybutyl>phosphonate | 123381-39-5

• 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: (2R,3S)-dimethyl <3-<<<(tert-butyloxycarbonyl)phenylalaninyl>histidyl>amino>-4-cyclohexyl-2-hydroxybutyl>phosphonate
• 英文别名: (2R,3S)-dimethyl [3-({[(tert-butyloxycarbonyl)phenylalaninyl]histidyl}amino)-4-cyclohexyl-2-hydroxybutyl]phosphonate；{3-[2-(2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)-3-(3H-imidazol-4-yl)-propionylamino]-4-cyclohexyl-2-hydroxy-butyl}-phosphonic acid dimethyl ester；tert-butyl N-[(2S)-1-[[(2S)-1-[[(2S,3R)-1-cyclohexyl-4-dimethoxyphosphoryl-3-hydroxybutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 123381-39-5
• 化学式: C₃₂H₅₀N₅O₈P
• 分子量: 663.751
• InChiKey: DOVBDVGFLOFMTQ-LJWNLINESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  46
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  181
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-甲基-2-丙基[(2S)-1-环己基-3-氧代-2-丙基]氨基甲酸酯 在 N-甲基吗啉 、 盐酸 、 正丁基锂 、 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， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (2R,3S)-dimethyl <3-<<<(tert-butyloxycarbonyl)phenylalaninyl>histidyl>amino>-4-cyclohexyl-2-hydroxybutyl>phosphonate
  参考文献：
  名称：

  New inhibitors of renin that contain novel phosphostatine Leu-Val replacements

  摘要：

  A novel series of renin inhibitors based on the Phe8-His9-Leu10-Val11 substructure of renin's natural substrate, angiotensinogen, is reported. These inhibitors retain the Phe8-His9 portion of the native substructure and employ novel phosphostatine Leu10-Val11 replacements (LVRs). The phosphostatine LVRs were prepared by condensing a dialkyl phosphonate ester stabilized anion with either N-t-Boc-amino aldehydes or N-tritylamino aldehydes (derived from the corresponding amino acid). Structure-activity relationships at the Leu10 side chain revealed that the LVR derived from L-cyclohexylalanine provided a 130-fold boost in potency over the LVR derived from L-leucine. The dialkyl ester moiety was varied and a loss in potency was incurred when the alkyl ester was chain extended or alpha-branched; dimethyl esters provided optimum potency. The phosphonate moiety was replaced by a half-acid half-ester phosphonate and dimethylphosphinate; both replacements lead to a loss in potency. The more potent inhibitors (IC50 = 20-50 nM) were found to be selective inhibitors for renin over porcine pepsin and bovine cathepsin D (little or no inhibition was observed at 10(-5) M).

  DOI：

  10.1021/jm00164a011