(4S,5R)-5-<(di-n-butylphosphinyl)methyl>-4-(cyclohexylmethyl)oxazolidin-2-one | 123381-33-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: (4S,5R)-5-<(di-n-butylphosphinyl)methyl>-4-(cyclohexylmethyl)oxazolidin-2-one
• CAS: 123381-33-9
• 化学式: C₁₉H₃₆NO₅P
• 分子量: 389.472
• InChiKey: GYQRHKGKMHGKGY-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.26
• 重原子数：
  26.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  73.86
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  L-环己基丙氨酸甲酯盐酸盐 在 palladium on activated charcoal 盐酸 、 lithium aluminium tetrahydride 、 草酰氯 、 氢气 、 仲丁基锂 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 为溶剂， -78.0~25.0 ℃ 、101.33 kPa 条件下， 反应 22.5h， 生成 (4S,5R)-5-<(di-n-butylphosphinyl)methyl>-4-(cyclohexylmethyl)oxazolidin-2-one
  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