(2S,4S,5S)-5-Amino-4-hydroxy-2-isopropyl-7-methyl-octanoic acid {(1S,2S)-1-[(S)-1-carbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-methyl-butyl}-amide | 102522-16-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (2S,4S,5S)-5-Amino-4-hydroxy-2-isopropyl-7-methyl-octanoic acid {(1S,2S)-1-[(S)-1-carbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-methyl-butyl}-amide
• 英文别名: (2S,4S,5S)-5-amino-N-[(2S,3S)-1-[[(2S)-1-amino-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]-4-hydroxy-7-methyl-2-propan-2-yloctanamide
• CAS: 102522-16-7
• 化学式: C₂₄H₄₄N₆O₄
• 分子量: 480.651
• InChiKey: KGADZPCHPCGVNO-SFOIOBPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  34
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  176
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,4S,5S)-5-Amino-4-hydroxy-2-isopropyl-7-methyl-octanoic acid {(1S,2S)-1-[(S)-1-carbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-methyl-butyl}-amide 、 Boc-Phe-His-OH 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， 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-((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 作用下， 以 甲醇 、 水 为溶剂， 反应 0.5h， 以78%的产率得到(2S,4S,5S)-5-Amino-4-hydroxy-2-isopropyl-7-methyl-octanoic acid {(1S,2S)-1-[(S)-1-carbamoyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-methyl-butyl}-amide
  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

• Verfahren zur Herstellung von 4,4',7,7'-Tetrachlorthioindigo-Pigmenten
  申请人：BAYER AG

  公开号：EP0129690A2

  公开（公告）日：1985-01-02

  Verfahren zur Herstellung von 4,4',7,7'-Tetrachlor-thioindigo-Pigmenten durch Oxidation von 3-Hydroxy-4,7-dichlor- 1-thionaphthen im wäßrig alkalischen Medium in Gegenwart von Sauerstoff oder Sauerstoff enthaltenden Gasen, dadurch gekennzeichnet, daß man das Reaktionsprodukt nach der Oxidation mit einer organischen Flüssigkeit, die vor, während oder nach der Oxidation zugesetzt wird, bei Temperaturen von etwa 60°C bis etwa 200°C etwa 2 h oder länger behandelt.

  在氧气或含氧气体存在下，通过在水性碱性介质中氧化 3-羟基-4,7-二氯-1-硫代萘，制备 4,4',7,7'-四氯硫代靛蓝颜料的工艺，该工艺包括在氧化前、氧化过程中或氧化后，在约 60°C 至约 200°C 的温度下，用有机液体处理氧化后的反应产物约 2 小时或更长时间。
• 5-Amino-4-Hydroxyvalerylderivate, als Zwischenprodukte in der Herstellung von Renin-Hemmern benutzbar
  申请人：CIBA-GEIGY AG

  公开号：EP0400290A1

  公开（公告）日：1990-12-05

  Verbindungen der Formel worin R3 Wasserstoff, Alkyl, Cycloalkyl, Arylniederalkyl oder Aryl, R4 Hydroxy oder veräthertes oder verestertes Hydroxy, R5 Alkyl, Cycloalkyl, Arylniederalkyl oder Aryl und R6 substituiertes Amino oder substituiertes Hydroxy darstellen, und Salze von solchen Verbindungen sind Zwischenprodukte zur Herstellung von Renininhibitoren.

  式中的化合物 其中 R3 为氢、烷基、环烷基、芳基-低级烷基或芳基，R4 为羟基或醚化或酯化羟基，R5 为烷基、环烷基、芳基-低级烷基或芳基，R6 为取代氨基或取代羟基，此类化合物及其盐类是制备肾素抑制剂的中间体。