3-mercapto-4-<2-(4-pyridyl)ethyl>-5-(trifluoromethyl)-4H-1,2,4-triazole | 141463-11-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-mercapto-4-<2-(4-pyridyl)ethyl>-5-(trifluoromethyl)-4H-1,2,4-triazole
• 英文别名: 4-(2-pyridin-4-ylethyl)-3-(trifluoromethyl)-1H-1,2,4-triazole-5-thione
• CAS: 141463-11-8
• 化学式: C₁₀H₉F₃N₄S
• 分子量: 274.269
• InChiKey: KBYAQXAKFDTLHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.22
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  43.6
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-mercapto-4-<2-(4-pyridyl)ethyl>-5-(trifluoromethyl)-4H-1,2,4-triazole 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 、 乙二醇甲醚 为溶剂， 反应 9.5h， 生成 tert-butyl 4-[(2S)-3-[[(2S,3R)-1-cyclohexyl-3-hydroxy-4-[[4-(2-pyridin-4-ylethyl)-5-(trifluoromethyl)-1,2,4-triazol-3-yl]sulfanyl]butan-2-yl]amino]-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-3-oxopropyl]imidazole-1-carboxylate
  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-(2-氨基乙基)吡啶 在 一水合肼 、 三乙胺 作用下， 以 乙二醇甲醚 为溶剂， 反应 10.75h， 生成 3-mercapto-4-<2-(4-pyridyl)ethyl>-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