[(1S,2R)-1-Cyclohexylmethyl-2-hydroxy-3-(4-methyl-pyrimidin-2-ylsulfanyl)-propyl]-carbamic acid tert-butyl ester | 141463-16-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: [(1S,2R)-1-Cyclohexylmethyl-2-hydroxy-3-(4-methyl-pyrimidin-2-ylsulfanyl)-propyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S,3R)-1-cyclohexyl-3-hydroxy-4-(4-methylpyrimidin-2-yl)sulfanylbutan-2-yl]carbamate
• CAS: 141463-16-3
• 化学式: C₂₀H₃₃N₃O₃S
• 分子量: 395.566
• InChiKey: YWUUFAHJNSZEMP-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  84.34
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  [(1S,2R)-1-Cyclohexylmethyl-2-hydroxy-3-(4-methyl-pyrimidin-2-ylsulfanyl)-propyl]-carbamic acid tert-butyl ester 在 氨 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 {(S)-1-[(S)-1-[(1S,2R)-1-Cyclohexylmethyl-2-hydroxy-3-(4-methyl-pyrimidin-2-ylsulfanyl)-propylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic 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：

  (2R,3S)-3-(t-butoxycarbonylamino)-4-cyclohexyl-1,2-epoxybutane 、 2-mercapto-6-methylpyrimidine 在 N-甲基吗啉 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以38%的产率得到[(1S,2R)-1-Cyclohexylmethyl-2-hydroxy-3-(4-methyl-pyrimidin-2-ylsulfanyl)-propyl]-carbamic 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