(3R,4S)-N-(3-((1-(cyanomethyl)cyclopropyl)methoxy)-5-(3-methoxypropyl)-benzyl)-N-cyclopropyl-4-{4-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)phenyl}-piperidine-3-carboxamide | 1026787-27-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3R,4S)-N-(3-((1-(cyanomethyl)cyclopropyl)methoxy)-5-(3-methoxypropyl)-benzyl)-N-cyclopropyl-4-{4-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)phenyl}-piperidine-3-carboxamide
• 英文别名: (3R,4S)-N-(3-((1-(cyanomethyl)cyclopropyl)methoxy)-5-(3-methoxypropyl)benzyl)-N-cyclopropyl-4-(4-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)phenyl)piperidine-3-carboxamide；(3R,4S)-N-[[3-[[1-(cyanomethyl)cyclopropyl]methoxy]-5-(3-methoxypropyl)phenyl]methyl]-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carboxamide
• CAS: 1026787-27-8
• 化学式: C₄₁H₄₉Cl₂N₃O₅
• 分子量: 734.763
• InChiKey: PRAXUIQVVJSJMP-XDSPJLLDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  51
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  93
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-溴-5-羟基苯甲醛 在 咪唑 、 盐酸 、 sodium tetrahydroborate 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 氢气 、 palladium diacetate 、 sodium carbonate 、 magnesium sulfate 、 N,N-二异丙基乙胺 、 三苯基膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.5h， 生成 (3R,4S)-N-(3-((1-(cyanomethyl)cyclopropyl)methoxy)-5-(3-methoxypropyl)-benzyl)-N-cyclopropyl-4-{4-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)phenyl}-piperidine-3-carboxamide
  参考文献：
  名称：

  The discovery and synthesis of potent zwitterionic inhibitors of renin

  摘要：

  The incorporation of a carboxylic acid within in a series of 3-amido-4-aryl substituted piperidines (represented by general structure 32) led to the discovery of potent, zwitterionic, renin inhibitors with improved off-target profiles (CYP3A4 time-dependent inhibition and hERG affinity) relative to analogous non-zwitterionic inhibitors of the past (i.e., 3). Strategies to address the oral absorption of these zwitterions are also discussed within. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.067

文献信息

• RENIN INHIBITORS
  申请人：Dube Daniel

  公开号：US20100063091A1

  公开（公告）日：2010-03-11

  The present invention relates to disubstituted piperidinyl renin inhibitor compounds having the structure (Formula I) and their use in treating cardiovascular events and renal insufficiency.

  本发明涉及具有结构式（式I）的二取代哌啶基肾素抑制剂化合物及其在治疗心血管事件和肾功能不全中的应用。
• US8076359B2
  申请人：——

  公开号：US8076359B2

  公开（公告）日：2011-12-13
• [EN] RENIN INHIBITORS<br/>[FR] INHIBITEURS DE LA RÉNINE
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2008058387A1

  公开（公告）日：2008-05-22

  [EN] The present invention relates to disubstituted piperidinyl renin inhibitor compounds having the structure (Formula I) and their use in treating cardiovascular events and renal insufficiency.
  [FR] La présente invention concerne des composés inhibiteurs de la rénine à base de pipéridinyle disubstitué de formule I et leur utilisation dans le traitement des complications cardiovasculaires et de l'insuffisance rénale.
• The discovery and synthesis of potent zwitterionic inhibitors of renin
  作者：Renee Aspiotis、Austin Chen、Elizabeth Cauchon、Daniel Dubé、Jean-Pierre Falgueyret、Sébastien Gagné、Michel Gallant、Erich L. Grimm、Robert Houle、Hélène Juteau、Patrick Lacombe、Sébastien Laliberté、Jean-François Lévesque、Dwight MacDonald、Dan McKay、M. David Percival、Patrick Roy、Stephen M. Soisson、Tom Wu

  DOI：10.1016/j.bmcl.2011.02.067

  日期：2011.4

  The incorporation of a carboxylic acid within in a series of 3-amido-4-aryl substituted piperidines (represented by general structure 32) led to the discovery of potent, zwitterionic, renin inhibitors with improved off-target profiles (CYP3A4 time-dependent inhibition and hERG affinity) relative to analogous non-zwitterionic inhibitors of the past (i.e., 3). Strategies to address the oral absorption of these zwitterions are also discussed within. (C) 2011 Elsevier Ltd. All rights reserved.