(3S,5R)-5-[(2,2-dimethoxy-1,1-dimethylethyl)amino]-N-(1-isobutyl-3-methylbutyl)-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxamide | 1448902-67-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S,5R)-5-[(2,2-dimethoxy-1,1-dimethylethyl)amino]-N-(1-isobutyl-3-methylbutyl)-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxamide
• CAS: 1448902-67-7
• 化学式: C₂₇H₄₆N₄O₇S
• 分子量: 570.751
• InChiKey: QMKORTOLCUWCDK-RBBKRZOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.54
• 重原子数：
  39.0
• 可旋转键数：
  14.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  140.11
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (3S,5R)-5-[(2,2-dimethoxy-1,1-dimethylethyl)amino]-N-(1-isobutyl-3-methylbutyl)-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxamide 在 盐酸 、 caesium carbonate 、 溶剂黄146 、 苯硫酚 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 47.91h， 生成 (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-N-(1-isobutyl-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：

  2-trimethylsilylethyl N-{(3R,5S)-5-[(1-isobutyl-3-methylbutyl)carbamoyl]-1-(2-nitrophenyl)sulfonyl-3-piperidyl}carbamate 在 四丁基氟化铵 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 55.0h， 生成 (3S,5R)-5-[(2,2-dimethoxy-1,1-dimethylethyl)amino]-N-(1-isobutyl-3-methylbutyl)-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxamide
  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