3-<<(2R,3S)-3-<(tert-butoxycarbonyl)-amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>-4-methyl-5-(trifluoromethyl)-4H-1,2,4-triazole | 141463-21-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 3-<<(2R,3S)-3-<(tert-butoxycarbonyl)-amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>-4-methyl-5-(trifluoromethyl)-4H-1,2,4-triazole
• 英文别名: tert-butyl N-[(2S,3R)-1-cyclohexyl-3-hydroxy-4-[[4-methyl-5-(trifluoromethyl)-1,2,4-triazol-3-yl]sulfanyl]butan-2-yl]carbamate
• CAS: 141463-21-0
• 化学式: C₁₉H₃₁F₃N₄O₃S
• 分子量: 452.541
• InChiKey: CWLIXFAUDLQNGG-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.15
• 重原子数：
  30.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  89.27
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3-<<(2R,3S)-3-<(tert-butoxycarbonyl)-amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>-4-methyl-5-(trifluoromethyl)-4H-1,2,4-triazole 在 盐酸 、 三乙胺 作用下， 生成 (2R,3S)-3-Amino-4-cyclohexyl-1-(4-methyl-5-trifluoromethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-butan-2-ol
  参考文献：
  名称：

  Renin inhibitors containing C-termini derived from mercaptoheterocycles

  摘要：

  A series of transition-state analogues having heterocyclylthio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. Oxidation of the thioether to sulfone was also investigated. Several of the compounds, especially those derived from N1-substituted-5-mercaptotetrazoles or N4-substituted-3-mercapto-5-(trifluoromethyl)-1,2,4-triazoles, were moderately potent inhibitors of human plasma renin, having IC50 values of 30-40 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys at 0.3-1.2 mg/kg, they reduced plasma renin activity by 75-98%. However, this inhibition and the accompanying drop in blood pressure were of short duration.

  DOI：

  10.1021/jm00089a023
• 作为产物：
  描述：

  4-甲基-5-三氟甲基-1,2,4-三唑-3-硫酮 、 (2R,3S)-3-(t-butoxycarbonylamino)-4-cyclohexyl-1,2-epoxybutane 在 四氯化锡 作用下， 以 四氯化碳 为溶剂， 反应 1.0h， 以65%的产率得到3-<<(2R,3S)-3-<(tert-butoxycarbonyl)-amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>-4-methyl-5-(trifluoromethyl)-4H-1,2,4-triazole
  参考文献：
  名称：

  Renin inhibitors containing C-termini derived from mercaptoheterocycles

  摘要：

  A series of transition-state analogues having heterocyclylthio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. Oxidation of the thioether to sulfone was also investigated. Several of the compounds, especially those derived from N1-substituted-5-mercaptotetrazoles or N4-substituted-3-mercapto-5-(trifluoromethyl)-1,2,4-triazoles, were moderately potent inhibitors of human plasma renin, having IC50 values of 30-40 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys at 0.3-1.2 mg/kg, they reduced plasma renin activity by 75-98%. However, this inhibition and the accompanying drop in blood pressure were of short duration.

  DOI：

  10.1021/jm00089a023