[4-((S)-2-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-2-{[(S)-6,7-dimethoxy-2-(morpholine-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl]-amino}-ethyl)-thiazol-2-yl]-carbamic acid benzyl ester | 142103-56-8

• 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: [4-((S)-2-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-2-{[(S)-6,7-dimethoxy-2-(morpholine-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl]-amino}-ethyl)-thiazol-2-yl]-carbamic acid benzyl ester
• CAS: 142103-56-8
• 化学式: C₄₄H₆₂N₆O₁₁S₂
• 分子量: 915.142
• InChiKey: VMMSESXDFSEWEZ-OZPXRHFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.16
• 重原子数：
  63.0
• 可旋转键数：
  19.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  218.19
• 氢给体数：
  5.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  [4-((S)-2-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-2-{[(S)-6,7-dimethoxy-2-(morpholine-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl]-amino}-ethyl)-thiazol-2-yl]-carbamic acid benzyl ester 在 palladium on activated charcoal 氢气 、 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以84%的产率得到<3S-<3R*>>-N-<1-<(2-aminothiazolyl)methyl>-2-<<1-(cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl>amino>-2-oxoethyl>-1,2,3,4-tetrahydro-6,7-dimethoxy-2-(4-morpholinylsulfonyl)-3-isoquinolinecarboxamide
  参考文献：
  名称：

  Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors

  摘要：

  A series of renin inhibitors was synthesized that contained a 2-amino-4-thiazolyl moiety at the P2 position. These derivatives are potent inhibitors of monkey renin in vitro and are selective in that they only weakly inhibit the closely related aspartic proteinase, bovine cathepsin D. Four compounds exhibited oral blood pressure lowering activity in high-renin normotensive monkeys. One of these compounds, 22 (PD 134672), was selected for further evaluation in renal hypertensive monkeys, on the basis of its superior efficacy and duration of action in the in vitro assays and the normotensive primate model.

  DOI：

  10.1021/jm00092a006
• 作为产物：
  描述：

  benzyl (2S)-3-(2-amino-1,3-thiazol-4-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate 在 盐酸 、 氢氧化钾 、 碳酸氢钠 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 [4-((S)-2-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-2-{[(S)-6,7-dimethoxy-2-(morpholine-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl]-amino}-ethyl)-thiazol-2-yl]-carbamic acid benzyl ester
  参考文献：
  名称：

  Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors

  摘要：

  A series of renin inhibitors was synthesized that contained a 2-amino-4-thiazolyl moiety at the P2 position. These derivatives are potent inhibitors of monkey renin in vitro and are selective in that they only weakly inhibit the closely related aspartic proteinase, bovine cathepsin D. Four compounds exhibited oral blood pressure lowering activity in high-renin normotensive monkeys. One of these compounds, 22 (PD 134672), was selected for further evaluation in renal hypertensive monkeys, on the basis of its superior efficacy and duration of action in the in vitro assays and the normotensive primate model.

  DOI：

  10.1021/jm00092a006