(4S,5S)-5-((S)-2-{(1S,2S)-1-[(S)-1-Carbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-methyl-butylcarbamoyl}-3-methyl-butyl)-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester | 102522-24-7

• 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: (4S,5S)-5-((S)-2-{(1S,2S)-1-[(S)-1-Carbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-methyl-butylcarbamoyl}-3-methyl-butyl)-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester
• CAS: 102522-24-7
• 化学式: C₃₅H₅₄N₆O₆
• 分子量: 654.85
• InChiKey: DMPKRMDLQWWXGL-OBXVVNIGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  47.0
• 可旋转键数：
  16.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  168.74
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (4S,5S)-5-((S)-2-{(1S,2S)-1-[(S)-1-Carbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-methyl-butylcarbamoyl}-3-methyl-butyl)-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 {(S)-1-[(S)-1-((1S,2S,4S)-4-{(1S,2S)-1-[(S)-1-Carbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-methyl-butylcarbamoyl}-2-hydroxy-1-isobutyl-5-methyl-hexylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester
  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：

  (4S,5S)-5-(2-Carboxy-3-methyl-butyl)-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester 、 H-Ile-His-NH2 在 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以81%的产率得到(4S,5S)-5-((S)-2-{(1S,2S)-1-[(S)-1-Carbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-methyl-butylcarbamoyl}-3-methyl-butyl)-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester
  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