tert-butyl N-[(2S,3R)-1-cyclohexyl-3-hydroxy-4-[[4-(2-pyridin-4-ylethyl)-5-(trifluoromethyl)-1,2,4-triazol-3-yl]sulfanyl]butan-2-yl]carbamate | 141483-73-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: tert-butyl N-[(2S,3R)-1-cyclohexyl-3-hydroxy-4-[[4-(2-pyridin-4-ylethyl)-5-(trifluoromethyl)-1,2,4-triazol-3-yl]sulfanyl]butan-2-yl]carbamate
• CAS: 141483-73-0
• 化学式: C₂₅H₃₆F₃N₅O₃S
• 分子量: 543.654
• InChiKey: CFPBDGIPWQKIFP-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.25
• 重原子数：
  37.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  102.16
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S,3R)-1-cyclohexyl-3-hydroxy-4-[[4-(2-pyridin-4-ylethyl)-5-(trifluoromethyl)-1,2,4-triazol-3-yl]sulfanyl]butan-2-yl]carbamate 在 盐酸 、 氨 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.5h， 生成 {1-[1-{1-Cyclohexylmethyl-2-hydroxy-3-[4-(2-pyridin-4-yl-ethyl)-5-trifluoromethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-propylcarbamoyl}-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester; hydrate
  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-(4-pyridyl)ethyl>-3-thiosemicarbazide 以 乙二醇甲醚 为溶剂， 反应 11.75h， 生成 tert-butyl N-[(2S,3R)-1-cyclohexyl-3-hydroxy-4-[[4-(2-pyridin-4-ylethyl)-5-(trifluoromethyl)-1,2,4-triazol-3-yl]sulfanyl]butan-2-yl]carbamate
  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