2-<<3-(benzyloxycarbonyl)-4-(cyclohexylmethyl)-2,2-dimethyl-(4S)-1,3-oxazolidin-5-yl>methyl>-3-methyl-(2S)-butyric acid | 105852-42-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-<<3-(benzyloxycarbonyl)-4-(cyclohexylmethyl)-2,2-dimethyl-(4S)-1,3-oxazolidin-5-yl>methyl>-3-methyl-(2S)-butyric acid
• 英文别名: 2-{[3-(benzyloxycarbonyl)-4-(cyclohexylmethyl)-2,2-dimethyl-(4S)-1,3-oxazolidin-5-yl]methyl}-3-methyl-(2S)-butyric acid；(2S)-2-[[(4S,5S)-4-(cyclohexylmethyl)-2,2-dimethyl-3-phenylmethoxycarbonyl-1,3-oxazolidin-5-yl]methyl]-3-methylbutanoic acid
• CAS: 105852-42-4
• 化学式: C₂₆H₃₉NO₅
• 分子量: 445.599
• InChiKey: JOMASUBYGZDAKX-VABKMULXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-<<3-(benzyloxycarbonyl)-4-(cyclohexylmethyl)-2,2-dimethyl-(4S)-1,3-oxazolidin-5-yl>methyl>-3-methyl-(2S)-butyric acid 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 、 HONB 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 75.0h， 生成 (2S,4S,5S)-5-[(S)-2-[(S)-2-Benzyl-3-(2-methyl-propane-2-sulfonyl)-propionylamino]-3-(1H-imidazol-4-yl)-propionylamino]-6-cyclohexyl-4-hydroxy-2-isopropyl-hexanoic acid butylamide
  参考文献：
  名称：

  Synthesis and biological activity of some transition-state inhibitors of human renin

  摘要：

  A series of renin inhibitors containing the dipeptide transition state mimics (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-7-methyloctanoic acid (Leu (OH)/Val) and (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-6-cyclohexylhexanoic acid (CHa /(OH)/Val) was prepared. A structure-activity study with Boc-Phe-His-Leu (OH)/Val-Ile-His-NH2 (8a) as starting material led to N-[(2S)-2-[(tert-butylsulfonyl)methyl]-3-phenylpropionyl]-His-Cha (OH)/ Val- NHC4H9-n (8i) which has the length of a tetrapeptide and contains only one natural amino acid. Compound 8i had an IC50 of 2 x 10(-9) M against human renin and showed high enzyme specificity; IC50 values against the related aspartic proteinases pepsin and cathepsin D were (8 x 10(-6) and 3 x 10(-6) M, respectively). In salt-depleted marmosets, 8i inhibited plasma renin activity PRA and lowered blood pressure for up to 2 h after oral administration of a dose of 10 mg/kg.

  DOI：

  10.1021/jm00117a027
• 作为产物：
  描述：

  异戊酸甲酯 在 正丁基锂 、 potassium tert-butylate 、 水 、 二异丙胺 作用下， 以 四氢呋喃 、 六甲基磷酰三胺 、 乙醚 为溶剂， 反应 20.5h， 生成 2-<<3-(benzyloxycarbonyl)-4-(cyclohexylmethyl)-2,2-dimethyl-(4S)-1,3-oxazolidin-5-yl>methyl>-3-methyl-(2S)-butyric acid
  参考文献：
  名称：

  Synthesis and biological activity of some transition-state inhibitors of human renin

  摘要：

  A series of renin inhibitors containing the dipeptide transition state mimics (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-7-methyloctanoic acid (Leu (OH)/Val) and (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-6-cyclohexylhexanoic acid (CHa /(OH)/Val) was prepared. A structure-activity study with Boc-Phe-His-Leu (OH)/Val-Ile-His-NH2 (8a) as starting material led to N-[(2S)-2-[(tert-butylsulfonyl)methyl]-3-phenylpropionyl]-His-Cha (OH)/ Val- NHC4H9-n (8i) which has the length of a tetrapeptide and contains only one natural amino acid. Compound 8i had an IC50 of 2 x 10(-9) M against human renin and showed high enzyme specificity; IC50 values against the related aspartic proteinases pepsin and cathepsin D were (8 x 10(-6) and 3 x 10(-6) M, respectively). In salt-depleted marmosets, 8i inhibited plasma renin activity PRA and lowered blood pressure for up to 2 h after oral administration of a dose of 10 mg/kg.

  DOI：

  10.1021/jm00117a027

文献信息

• US5091425A
  申请人：——

  公开号：US5091425A

  公开（公告）日：1992-02-25