| 130405-91-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• CAS: 130405-91-3；130466-61-4
• 化学式: C₅₄H₆₆N₁₀O₅
• 分子量: 935.182
• InChiKey: IDZHCMWRAWFWTD-FWVLGQQLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.09
• 重原子数：
  69.0
• 可旋转键数：
  22.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  194.49
• 氢给体数：
  4.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  在 palladium on activated charcoal ammonium formate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 (3R,4S)-3-Amino-5-cyclohexyl-4-[(S)-2-(8-isobutyl-6-phenyl-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)-3-pyridin-3-yl-propionylamino]-pentanoic acid {(S)-3-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butyl}-amide 、 (3R,4S)-3-Amino-5-cyclohexyl-4-[(R)-2-(8-isobutyl-6-phenyl-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)-3-pyridin-3-yl-propionylamino]-pentanoic acid {(S)-3-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butyl}-amide
  参考文献：
  名称：

  1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 3. Synthesis and biological properties of aminodeoxystatine and difluorostatone derivatives

  摘要：

  Two series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity have been synthesized which incorporate the transition-state mimetics (3S,4S)- and (3R,4S)-5-cyclohexyl-3,4-diaminopentanoic acid ((S)- and (R)-CDAPA), and (4S)-4-amino-5-cyclohexyl-2,2-difluoro-3-oxopentanoic acid (ACDFOPA). Several compounds in these series, for example 13a, 19c, and 19f, were highly potent inhibitors of partially purified human renin (IC50 values of 3.9, 1.6, and 1.4 nM, respectively). The ACDFOPA-based compounds 19c and 19f contain no natural amino acid fragments and have molecular weights which compare well with those of previously reported inhibitors to nanomolar in vitro potency. When administered intravenously to anesthetized, sodium-depleted marmosets at doses of 3 mg/kg, compounds 13a and 19c caused a marked reduction in mean arterial pressure, but in the same animal model at 30 mg/kg, oral activity was not seen.

  DOI：

  10.1021/jm00105a022
• 作为产物：
  描述：

  在 盐酸 、 sodium hydroxide 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 3. Synthesis and biological properties of aminodeoxystatine and difluorostatone derivatives

  摘要：

  Two series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity have been synthesized which incorporate the transition-state mimetics (3S,4S)- and (3R,4S)-5-cyclohexyl-3,4-diaminopentanoic acid ((S)- and (R)-CDAPA), and (4S)-4-amino-5-cyclohexyl-2,2-difluoro-3-oxopentanoic acid (ACDFOPA). Several compounds in these series, for example 13a, 19c, and 19f, were highly potent inhibitors of partially purified human renin (IC50 values of 3.9, 1.6, and 1.4 nM, respectively). The ACDFOPA-based compounds 19c and 19f contain no natural amino acid fragments and have molecular weights which compare well with those of previously reported inhibitors to nanomolar in vitro potency. When administered intravenously to anesthetized, sodium-depleted marmosets at doses of 3 mg/kg, compounds 13a and 19c caused a marked reduction in mean arterial pressure, but in the same animal model at 30 mg/kg, oral activity was not seen.

  DOI：

  10.1021/jm00105a022