4-((S)-1-{(S)-1-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-2-[2-(2,2,2-trichloro-ethoxycarbonylamino)-thiazol-4-yl]-ethylcarbamoyl}-2-phenyl-ethylsulfamoyl)-piperazine-1-carboxylic acid 2,2,2-trichloro-ethyl ester | 135704-09-5

• 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)-1-{(S)-1-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-2-[2-(2,2,2-trichloro-ethoxycarbonylamino)-thiazol-4-yl]-ethylcarbamoyl}-2-phenyl-ethylsulfamoyl)-piperazine-1-carboxylic acid 2,2,2-trichloro-ethyl ester
• CAS: 135704-09-5
• 化学式: C₃₉H₅₅Cl₆N₇O₁₀S₂
• 分子量: 1058.76
• InChiKey: YAGFZWQEAPJTLM-QEUNAIBPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.88
• 重原子数：
  64.0
• 可旋转键数：
  20.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  228.83
• 氢给体数：
  6.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  4-((S)-1-{(S)-1-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-2-[2-(2,2,2-trichloro-ethoxycarbonylamino)-thiazol-4-yl]-ethylcarbamoyl}-2-phenyl-ethylsulfamoyl)-piperazine-1-carboxylic acid 2,2,2-trichloro-ethyl ester 在 氯化铵 、 锌 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 9.5h， 以72%的产率得到<1S-(1R*,2S*,3R*)>-N-(1-piperazinylsulfonyl)-L-phenylalanyl-3-(2-amino-4-thiazolyl)-N-<1-(cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl>-L-alaninamide
  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：

  4-((S)-1-Carboxy-2-phenyl-ethylsulfamoyl)-piperazine-1-carboxylic acid 2,2,2-trichloro-ethyl ester 、 {4-[(S)-2-Amino-2-((1S,2R,3S)-1-cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-ethyl]-thiazol-2-yl}-carbamic acid 2,2,2-trichloro-ethyl ester 在 1-羟基苯并三唑 、 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88%的产率得到4-((S)-1-{(S)-1-((1S,2R,3S)-1-Cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-2-[2-(2,2,2-trichloro-ethoxycarbonylamino)-thiazol-4-yl]-ethylcarbamoyl}-2-phenyl-ethylsulfamoyl)-piperazine-1-carboxylic acid 2,2,2-trichloro-ethyl 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