methyl (3S,5R)-5-{[2-(5-fluoro-2-methylanilino)-1,1-dimethylethyl]amino}-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxylate | 1263198-53-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl (3S,5R)-5-{[2-(5-fluoro-2-methylanilino)-1,1-dimethylethyl]amino}-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxylate
• CAS: 1263198-53-3
• 化学式: C₂₄H₃₁FN₄O₆S
• 分子量: 522.598
• InChiKey: SJSDRBLNPPWYKQ-PKOBYXMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.07
• 重原子数：
  36.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  130.88
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  methyl (3S,5R)-5-{[2-(5-fluoro-2-methylanilino)-1,1-dimethylethyl]amino}-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxylate 在 lithium hydroxide monohydrate 、 碳酸氢钠 、 caesium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 苯硫酚 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 29.58h， 生成 (3S,5R)-5-[4-(5-fluoro-2-methylphenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-N-[(1R)-1-(5-fluoro-2-pyridyl)-3-methylbutyl]piperidine-3-carboxamide fumarate
  参考文献：
  名称：

  Synthesis and optimization of novel (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as orally active renin inhibitors

  摘要：

  We report synthesis and optimization of a series of (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as renin inhibitors. Chemical modification of P-1', P-2' and P-3 portions led to a promising 3,5-disubstituted piperidine 32o showing high renin inhibitory activity and favorable oral exposure in both rats and cynomolgus monkeys with acceptable CYP and hERG current inhibition. Compound 32o exhibited a significant blood pressure lowering effect by oral administration in two hypertensive animal models, double transgenic rats and furosemide pretreated cynomolgus monkeys. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.057
• 作为产物：
  描述：

  1-tert-Butyl 3-methyl (3S,5R)-5-[(1,1-dimethyl-2-oxoethyl)amino]piperidine-1,3-dicarboxylate 在 盐酸 、 碳酸氢钠 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 水 、 甲苯 为溶剂， 反应 22.0h， 生成 methyl (3S,5R)-5-{[2-(5-fluoro-2-methylanilino)-1,1-dimethylethyl]amino}-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxylate
  参考文献：
  名称：

  Synthesis and optimization of novel (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as orally active renin inhibitors

  摘要：

  We report synthesis and optimization of a series of (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as renin inhibitors. Chemical modification of P-1', P-2' and P-3 portions led to a promising 3,5-disubstituted piperidine 32o showing high renin inhibitory activity and favorable oral exposure in both rats and cynomolgus monkeys with acceptable CYP and hERG current inhibition. Compound 32o exhibited a significant blood pressure lowering effect by oral administration in two hypertensive animal models, double transgenic rats and furosemide pretreated cynomolgus monkeys. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.057