(rac.)-(3R*,4S*)3'-{[2-chloro-5-(3-methoxy-propyl)-benzyl]-cyclopropyl-carbamoyl}-6-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-3',4',5',6'-tetrahydro-2'H-[3,4']bipyridinyl-1'-carboxylic acid tert-butyl ester

• 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: (rac.)-(3R*,4S*)3'-{[2-chloro-5-(3-methoxy-propyl)-benzyl]-cyclopropyl-carbamoyl}-6-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-3',4',5',6'-tetrahydro-2'H-[3,4']bipyridinyl-1'-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (3R,4S)-3-[[2-chloro-5-(3-methoxypropyl)phenyl]methyl-cyclopropylcarbamoyl]-4-[6-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]pyridin-3-yl]piperidine-1-carboxylate
• 化学式: C₃₉H₄₈Cl₃N₃O₆
• 分子量: 761.186
• InChiKey: YOQPZNCLRPQLNT-JSOSNVBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  51
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  90.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (rac.)-(3R*,4S*)3'-{[2-chloro-5-(3-methoxy-propyl)-benzyl]-cyclopropyl-carbamoyl}-6-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-3',4',5',6'-tetrahydro-2'H-[3,4']bipyridinyl-1'-carboxylic acid tert-butyl ester 在 盐酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 以63%的产率得到(3'R,4'S)-6-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-3'-carboxylic acid [2-chloro-5-(3-methoxy-propyl)-benzyl]-cyclopropyl-amide
  参考文献：
  名称：

  Novel Piperidine Carboxylic Acid Amide Derivatives

  摘要：

  本发明涉及新型的哌啶羧酸酰胺衍生物及其作为活性成分用于制备药物组合物。本发明还涉及相关方面，包括这些新型化合物的制备方法、包含此类化合物的药物组合物，尤其是此类化合物作为肾素抑制剂的应用。

  公开号：

  US20080214598A1
• 作为产物：
  描述：

  N-({2-氯-5-[3-(甲基氧基)丙基]苯基}甲基)环丙胺 、 (rac.)-(3R*,4S*)-6-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)-3',4',5',6'-tetrahydro-2'H-[3,4']bipyridinyl-1',3'-dicarboxylic acid 1'-tert-butyl ester 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 生成 (rac.)-(3R*,4S*)3'-{[2-chloro-5-(3-methoxy-propyl)-benzyl]-cyclopropyl-carbamoyl}-6-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-3',4',5',6'-tetrahydro-2'H-[3,4']bipyridinyl-1'-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Piperidine-based renin inhibitors: Upper chain optimization

  摘要：

  The optimization of the 4-position of recently described new 3,4-disubstituted piperidine-based renin inhibitors is reported herein. The synthesis and characterization of compounds leading to the discovery of 11 (ACT-178882, MK-1597), a renin inhibitor with a suitable profile for development is described. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.087

文献信息

• Novel Piperidine Carboxylic Acid Amide Derivatives
  申请人：Bezencon Olivier

  公开号：US20080214598A1

  公开（公告）日：2008-09-04

  The invention relates to novel piperidine carboxylic acid amide derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of these novel compounds, pharmaceutical compositions comprising such compounds and especially the use of such compounds as inhibitors of renin.

  本发明涉及新型的哌啶羧酸酰胺衍生物及其作为活性成分用于制备药物组合物。本发明还涉及相关方面，包括这些新型化合物的制备方法、包含此类化合物的药物组合物，尤其是此类化合物作为肾素抑制剂的应用。
• Piperidine-based renin inhibitors: Upper chain optimization
  作者：Olivier Corminboeuf、Olivier Bezençon、Ľuboš Remeň、Corinna Grisostomi、Sylvia Richard-Bildstein、Daniel Bur、Lars Prade、Panja Strickner、Patrick Hess、Walter Fischli、Beat Steiner、Alexander Treiber

  DOI：10.1016/j.bmcl.2010.08.087

  日期：2010.11

  The optimization of the 4-position of recently described new 3,4-disubstituted piperidine-based renin inhibitors is reported herein. The synthesis and characterization of compounds leading to the discovery of 11 (ACT-178882, MK-1597), a renin inhibitor with a suitable profile for development is described. (C) 2010 Elsevier Ltd. All rights reserved.