(3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-N-(1-isobutyl-3-methylbutyl)-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxamide | 1415413-47-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-N-(1-isobutyl-3-methylbutyl)-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxamide
• 英文别名: (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-N-(2,6-dimethylheptan-4-yl)-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxamide
• CAS: 1415413-47-6
• 化学式: C₃₃H₄₆ClN₅O₆S
• 分子量: 676.277
• InChiKey: DHCMAHCVMZUOTC-AZGAKELHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  144
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-N-(1-isobutyl-3-methylbutyl)-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxamide 在 caesium carbonate 、 苯硫酚 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 1.52h， 生成 (E)-but-2-enedioic acid;(3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-N-(2,6-dimethylheptan-4-yl)piperidine-3-carboxamide
  参考文献：
  名称：

  Design and discovery of new (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides as potent renin inhibitors

  摘要：

  Utilizing X-ray crystal structure analysis, (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides were designed and identified as renin inhibitors. The most potent compound 15 demonstrated favorable pharmacokinetic and pharmacodynamic profiles in rat. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.103
• 作为产物：
  描述：

  (3S,5R)-5-((2-methyl-1-oxopropan-2-yl)amino)-1-((2-nitrophenyl)sulfonyl)piperidine-3-carboxylic acid 在 氯化亚砜 、 水 、 sodium cyanoborohydride 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 19.5h， 生成 (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-N-(1-isobutyl-3-methylbutyl)-1-(2-nitrophenyl)sulfonylpiperidine-3-carboxamide
  参考文献：
  名称：

  Design and discovery of new (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides as potent renin inhibitors

  摘要：

  Utilizing X-ray crystal structure analysis, (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides were designed and identified as renin inhibitors. The most potent compound 15 demonstrated favorable pharmacokinetic and pharmacodynamic profiles in rat. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.103

文献信息

• 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
  作者：Yutaka Mori、Yasuyuki Ogawa、Akiyoshi Mochizuki、Yuji Nakamura、Teppei Fujimoto、Chie Sugita、Shojiro Miyazaki、Kazuhiko Tamaki、Takahiro Nagayama、Yoko Nagai、Shin-ichi Inoue、Katsuyoshi Chiba、Takahide Nishi

  DOI：10.1016/j.bmc.2013.06.057

  日期：2013.9

  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.
• Design and discovery of new (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides as potent renin inhibitors
  作者：Yutaka Mori、Yasuyuki Ogawa、Akiyoshi Mochizuki、Yuji Nakamura、Chie Sugita、Shojiro Miyazaki、Kazuhiko Tamaki、Yumi Matsui、Mizuki Takahashi、Takahiro Nagayama、Yoko Nagai、Shin-ichi Inoue、Takahide Nishi

  DOI：10.1016/j.bmcl.2012.09.103

  日期：2012.12

  Utilizing X-ray crystal structure analysis, (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides were designed and identified as renin inhibitors. The most potent compound 15 demonstrated favorable pharmacokinetic and pharmacodynamic profiles in rat. (C) 2012 Elsevier Ltd. All rights reserved.