tert-butyl (3R,4S)-3-(((3-((1-(cyanomethyl)cyclopropyl)methoxy)-5-(3-methoxypropyl)-benzyl)(cyclopropyl)amino)carbonyl)-4-(4-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)phenyl)-piperidine-1-carboxylate | 1026787-28-9

• 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: tert-butyl (3R,4S)-3-(((3-((1-(cyanomethyl)cyclopropyl)methoxy)-5-(3-methoxypropyl)-benzyl)(cyclopropyl)amino)carbonyl)-4-(4-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)phenyl)-piperidine-1-carboxylate
• 英文别名: tert-Butyl (3R,4S)-3-{[[3-{[1-(cyanomethyl)cyclopropyl]methoxy}-5-(3-methoxypropyl)benzyl](cyclopropyl)amino]carbonyl}-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-1-carboxylate；tert-butyl (3R,4S)-3-[[3-[[1-(cyanomethyl)cyclopropyl]methoxy]-5-(3-methoxypropyl)phenyl]methyl-cyclopropylcarbamoyl]-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-1-carboxylate
• CAS: 1026787-28-9
• 化学式: C₄₆H₅₇Cl₂N₃O₇
• 分子量: 834.88
• InChiKey: WJMQMENVGJXIFR-RGULYWFUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  58
• 可旋转键数：
  20
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl (3R,4S)-3-(((3-((1-(cyanomethyl)cyclopropyl)methoxy)-5-(3-methoxypropyl)-benzyl)(cyclopropyl)amino)carbonyl)-4-(4-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)phenyl)-piperidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 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
• 作为产物：
  描述：

  1-羟甲基环丙基乙腈 在 caesium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 tert-butyl (3R,4S)-3-(((3-((1-(cyanomethyl)cyclopropyl)methoxy)-5-(3-methoxypropyl)-benzyl)(cyclopropyl)amino)carbonyl)-4-(4-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)phenyl)-piperidine-1-carboxylate
  参考文献：
  名称：

  WO2008/141462

  摘要：

  公开号：

文献信息

• NOVEL CASE OF RENIN INHIBITORS
  申请人：Wu Tom Yao-Hsiang

  公开号：US20100120859A1

  公开（公告）日：2010-05-13

  The present invention relates to piperidine-based renin inhibitor compounds having carboxylate or carboxylic acid terminal groups, and their use in treating cardiovascular events and renal insufficiency.

  本发明涉及基于哌啶的肾素抑制剂化合物，其具有羧酸盐或羧酸末端基团，并且它们在治疗心血管事件和肾功能不全方面的使用。
• Case of renin inhibitors
  申请人：Merck Canada Inc.

  公开号：US08343968B2

  公开（公告）日：2013-01-01

  The present invention relates to piperidine-based renin inhibitor compounds having carboxylate or carboxylic acid terminal groups, and their use in treating cardiovascular events and renal insufficiency.

  本发明涉及以哌啶为基础的肾素抑制剂化合物，其具有羧酸盐或羧酸末端基团，并且它们在治疗心血管事件和肾功能不全方面的用途。
• WO2008/58387
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2008/141462
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.