((2R,3S)-3-Amino-4-cyclohexyl-2-hydroxy-butyl)-phosphonic acid dimethyl ester; hydrochloride | 123381-48-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: ((2R,3S)-3-Amino-4-cyclohexyl-2-hydroxy-butyl)-phosphonic acid dimethyl ester; hydrochloride
• CAS: 123381-48-6
• 化学式: C₁₂H₂₆NO₄P*ClH
• 分子量: 315.777
• InChiKey: AWUZJDDGCDEEQA-FXMYHANSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.55
• 重原子数：
  19.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  81.78
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (R)-methoxytrifluoromethylphenylacetyl chloride 、 ((2R,3S)-3-Amino-4-cyclohexyl-2-hydroxy-butyl)-phosphonic acid dimethyl ester; hydrochloride 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以50%的产率得到[(2R,3S)-4-Cyclohexyl-2-hydroxy-3-(3,3,3-trifluoro-2-methoxy-2-phenyl-propionylamino)-butyl]-phosphonic acid dimethyl ester
  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
• 作为产物：
  描述：

  (2R,3S)-dimethyl <3-(t-Boc-amino)-4-cyclohexyl-2-hydroxybutyl>phosphonate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 ((2R,3S)-3-Amino-4-cyclohexyl-2-hydroxy-butyl)-phosphonic acid dimethyl ester; hydrochloride
  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