(3R,4S)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-3-carboxylic acid (cyclopropyl)(3-(3-methoxypropyl)-5-{[1-(2H-tetrazol-5-ylmethyl)cyclopropyl]methoxy}benzyl)amide | 1087347-18-9

• 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: (3R,4S)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-3-carboxylic acid (cyclopropyl)(3-(3-methoxypropyl)-5-{[1-(2H-tetrazol-5-ylmethyl)cyclopropyl]methoxy}benzyl)amide
• 英文别名: (3R,4S)-N-(3-((1-((2H-tetrazol-5-yl)methyl)cyclopropyl)methoxy)-5-(3-methoxypropyl)benzyl)-N-cyclopropyl-4-(4-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)phenyl)piperidine-3-carboxamide；(3R,4S)-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-N-[[3-(3-methoxypropyl)-5-[[1-(2H-tetrazol-5-ylmethyl)cyclopropyl]methoxy]phenyl]methyl]piperidine-3-carboxamide
• CAS: 1087347-18-9
• 化学式: C₄₁H₅₀Cl₂N₆O₅
• 分子量: 777.791
• InChiKey: UQAYVLAYSNHNRH-GPOMZPHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  54
• 可旋转键数：
  19
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  9

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-) 、 三正丁基叠氮化锡 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)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-3-carboxylic acid (cyclopropyl)(3-(3-methoxypropyl)-5-{[1-(2H-tetrazol-5-ylmethyl)cyclopropyl]methoxy}benzyl)amide
  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

• 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。
• US8343968B2
  申请人：——

  公开号：US8343968B2

  公开（公告）日：2013-01-01
• [EN] NOVEL CASE OF RENIN INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE RHÉNINE
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2008141462A1

  公开（公告）日：2008-11-27

  [EN] The present invention relates to piperidine-based renin inhibitor compounds having carboxylate or carboxylic acid terminal groups. The disclosed low molecular weight, orally active renin inhibitors are of non-peptide nature and have long duration of action. The compounds can be used in the treatment of cardiovascular events and renal insufficiency.
  [FR] L'invention concerne des composés inhibiteurs de rhénine à base de pipéridine renfermant des groupes terminaux carboxylate ou acide carboxylique. Les inhibiteurs de rhénine de l'invention, qui possèdent un faible poids moléculaire et une activité orale, sont de nature non peptidique et exercent une action de longue durée. Les composés précités peuvent être utilisés dans le traitement d'événements 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.