(3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-N-[(1R)-1-(5-fluoropyridin-2-yl)-3-methylbutyl]piperidine-3-carboxamide | 1263197-21-2

• 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-[(1R)-1-(5-fluoropyridin-2-yl)-3-methylbutyl]piperidine-3-carboxamide
• CAS: 1263197-21-2
• 化学式: C₂₈H₃₇ClFN₅O₂
• 分子量: 530.085
• InChiKey: ARAQVWPNKFJBQQ-XZDHIHRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  77.6
• 氢给体数：
  2
• 氢受体数：
  6

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-[(1R)-1-(5-fluoropyridin-2-yl)-3-methylbutyl]piperidine-3-carboxamide 、 fumaric acid 以 甲醇 为溶剂， 反应 0.08h， 生成 (3S,5R)-5-[4-(2-chlorophenyl)-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：

  methyl (3S,5R)-5-[(1,1-dimethyl-2-oxoethyl)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 、 溶剂黄146 、 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 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 49.5h， 生成 (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-N-[(1R)-1-(5-fluoropyridin-2-yl)-3-methylbutyl]piperidine-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

文献信息

• [EN] SUBSTITUTED PIPERIDINE COMPOUND<br/>[FR] COMPOSÉ DE PIPÉRIDINE SUBSTITUÉ
  申请人：DAIICHI SANKYO CO LTD

  公开号：WO2011013644A1

  公开（公告）日：2011-02-03

  本発明は、高血圧症等の治療薬として有用な置換ピペリジン化合物を提供する。 本発明は、一般式（I）［式中、Ｒ1：Ｈ、置換可アルキル、フェニル、飽和環状炭化水素、ヘテロシクリル等；Ｒ2：Ｈ、アルキル；Ｒ3、Ｒ4：Ｈ、アルキル；Ａ：フェニル、ピリジル；Ｒ5、Ｒ6、Ｒ7：Ｈ、置換可アルキル、置換可ヒドロキシ、置換可メルカプト、置換可アミノ、置換カルボニル、置換スルホニル、ＣＮ、ＮＯ2、ハロゲノ等］を有する化合物等を提供する。
• 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.