ethyl 2-<5-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>-1H-tetrazol-1-yl>acetate | 141463-29-8

• 分子结构分类: 有机化合物 - 有机硫化合物
• 英文名称: ethyl 2-<5-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>-1H-tetrazol-1-yl>acetate
• 英文别名: ethyl 2-[5-[(2R,3S)-4-cyclohexyl-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]sulfanyltetrazol-1-yl]acetate
• CAS: 141463-29-8
• 化学式: C₂₀H₃₅N₅O₅S
• 分子量: 457.594
• InChiKey: ONCJREAGDLYPSO-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.55
• 重原子数：
  31.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  128.46
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-<5-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>-1H-tetrazol-1-yl>acetate 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.5h， 生成 4-{(S)-2-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)-2-[(1S,2R)-1-cyclohexylmethyl-3-(1-ethoxycarbonylmethyl-1H-tetrazol-5-ylsulfanyl)-2-hydroxy-propylcarbamoyl]-ethyl}-imidazole-1-carboxylic acid tert-butyl ester
  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：

  ethyl 2-(5-mercapto-1H-tetrazol-1-yl)acetate 、 (2R,3S)-3-(t-butoxycarbonylamino)-4-cyclohexyl-1,2-epoxybutane 在 N-甲基吗啉 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以83%的产率得到ethyl 2-<5-<<(2R,3S)-3-<(tert-butoxycarbonyl)amino>-4-cyclohexyl-2-hydroxy-1-butyl>thio>-1H-tetrazol-1-yl>acetate
  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