N-({1-[(4-hydroxypiperidin-4-yl)methyl]piperidine-4-yl}methyl)-1-isopropyl-5-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide ethanedioate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-({1-[(4-hydroxypiperidin-4-yl)methyl]piperidine-4-yl}methyl)-1-isopropyl-5-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide ethanedioate
• 英文别名: N-({1-[(4-Hydroxypiperidin-4-YL)methyl]piperidine-4-YL}methyl)-1-isopropyl-5-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide ethanedioate；N-[[1-[(4-hydroxypiperidin-4-yl)methyl]piperidin-4-yl]methyl]-5-methyl-2-oxo-1-propan-2-ylquinoline-3-carboxamide;oxalic acid
• 化学式: C₂H₂O₄*C₂₆H₃₈N₄O₃
• 分子量: 544.648
• InChiKey: HFVGGKCZWDNPRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  160
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  tert-butyl 4-hydroxy-4-{[4-({[(1-isopropyl-5-methyl-2-oxo-1,2dihydroquinolin-3-yl)carbonyl]amino}methyl)piperidine-1-yl]methyl}piperidine-1-carboxylate 、 草酸 在 盐酸 、 potassium carbonate 作用下， 以 甲醇 、 四氢呋喃 为溶剂， 反应 0.67h， 以74%的产率得到N-({1-[(4-hydroxypiperidin-4-yl)methyl]piperidine-4-yl}methyl)-1-isopropyl-5-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide ethanedioate
  参考文献：
  名称：

  [EN] QUINOLONECARBOXYLIC ACID COMPOUNDS HAVING 5-HT4 RECEPTOR AGONISTIC ACTIVITY
  [FR] COMPOSES D'ACIDE QUINOLONECARBOXYLIQUE A ACTIVITE AGONISTE DU RECEPTEUR 5-HT4

  摘要：

  该发明提供了一种化合物，其化学式为（I）：其中Het代表含有一个氮原子的杂环基团，其中B直接结合，含有从4到7个碳原子，该杂环基团未取代或者取代1到4个独立选择自α1取代基的取代基；A代表含有从1到4个碳原子的烷基基团；B代表共价键或含有从1到5个碳原子的烷基基团；R1代表异丙基基团、正丙基基团或环戊基团；R2代表甲基基团、氟原子或氯原子；R3独立代表（i）酮基、羟基、氨基、烷基氨基或羧基；（ii）含有从3到8个碳原子的环烷基团，该环烷基团被1到5个取代基取代；或（iii）含有从3到8个原子的杂环基团，该杂环基团未取代或者取代1到5个取代基，n为1、2或3，或其药学上可接受的盐。这些化合物具有5-HT4受体激动活性，因此对于哺乳动物，特别是人类的胃食管反流病、非溃疡性消化不良、功能性消化不良、肠易激综合征等的治疗是有用的。

  公开号：

  WO2005049608A1

文献信息

• Quinolonecarboxylic acid compounds having 5-HT4 receptor agonistic activity
  申请人：Pfizer Inc.

  公开号：US07964727B2

  公开（公告）日：2011-06-21

  This invention provides a compound of the formula (I): wherein Het represents a heterocyclic group having one nitrogen atom, to which B binds directly, and from 4 to 7 carbon atoms, and said heterocyclic group being unsubstituted or substituted by 1 to 4 substituents independently selected from the group consisting of substituents α1; A represents an alkylene group having from 1 to 4 carbon atoms; B represents a covalent bond or an alkylene group having from 1 to 5 carbon atoms; R1 represents an isopropyl group, a n-propyl group or a cyclopentyl group; R2 represents a methyl group, a fluorine atom or a chlorine atom; R3 independently represents (i) an oxo group, a hydroxy group, an amino group, an alkylamino group or a carboxyl group; (ii) a cycloalkyl group having from 3 to 8 carbon atoms, and said cycloalkyl group being substituted by 1 to 5 substituents, or (iii) a heterocyclic group having from 3 to 8 atoms, and said heterocyclic group being unsubstituted or substituted by 1 to 5 substituents, and n is 1, 2 or 3, or a pharmaceutically acceptable salts thereof. These compounds have 5-HT4 receptor agonistic activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans.

  该发明提供了一种式(I)的化合物：其中，Het代表一个杂环基团，其中有一个氮原子，B直接结合到该氮原子上，该杂环基团具有4到7个碳原子，且该杂环基团未取代或被1到4个独立选择的取代基α1取代；A代表具有1到4个碳原子的烷基链；B代表共价键或具有1到5个碳原子的烷基链；R1代表异丙基基团、正丙基基团或环戊基基团；R2代表甲基基团、氟原子或氯原子；R3独立地表示（i）氧代基、羟基、氨基、烷基氨基或羧基；（ii）具有3到8个碳原子的环烷基团，该环烷基团被1到5个取代基取代；或（iii）具有3到8个原子的杂环基团，该杂环基团未取代或被1到5个取代基取代，n为1、2或3，或其药学上可接受的盐。这些化合物具有5-HT4受体激动活性，因此可用于哺乳动物，特别是人类的胃食管反流病、非溃疡性消化不良、功能性消化不良、肠易激综合征等的治疗。
• [EN] QUINOLONECARBOXYLIC ACID COMPOUNDS HAVING 5-HT4 RECEPTOR AGONISTIC ACTIVITY<br/>[FR] COMPOSES D'ACIDE QUINOLONECARBOXYLIQUE A ACTIVITE AGONISTE DU RECEPTEUR 5-HT4
  申请人：PFIZER JAPAN INC

  公开号：WO2005049608A1

  公开（公告）日：2005-06-02

  This invention provides a compound of the formula (I): wherein Het represents a heterocyclic group having one nitrogen atom, to which B binds directly, and from 4 to 7 carbon atoms, and said heterocyclic group being unsubstituted or substituted by 1 to 4 substituents independently selected from the group consisting of substituents α1;A represents an alkylene group having from 1 to 4 carbon atoms; B represents a covalent bond or an alkylene group having from 1 to 5 carbon atoms; Rl represents an isopropyl group, a n-propyl group or a cyclopentyl group; R2 represents a methyl group, a fluorine atom or a chlorine atom; R3 independently represents (i) an oxo group, a hydroxy group, an amino group, an alkylamino group or a carboxyl group; (ii) a cycloalkyl group having from 3 to 8 carbon atoms, and said cycloalkyl group being substituted by 1 to 5 substituents, or (iii) a heterocyclic group having from 3 to 8 atoms, and said heterocyclic group being unsubstituted or substituted by 1 to 5 substituents, and n is 1, 2 or 3, or a pharmaceutically acceptable salts thereof. These compounds have 5-HT4 receptor agonistic activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans.

  该发明提供了一种化合物，其化学式为（I）：其中Het代表含有一个氮原子的杂环基团，其中B直接结合，含有从4到7个碳原子，该杂环基团未取代或者取代1到4个独立选择自α1取代基的取代基；A代表含有从1到4个碳原子的烷基基团；B代表共价键或含有从1到5个碳原子的烷基基团；R1代表异丙基基团、正丙基基团或环戊基团；R2代表甲基基团、氟原子或氯原子；R3独立代表（i）酮基、羟基、氨基、烷基氨基或羧基；（ii）含有从3到8个碳原子的环烷基团，该环烷基团被1到5个取代基取代；或（iii）含有从3到8个原子的杂环基团，该杂环基团未取代或者取代1到5个取代基，n为1、2或3，或其药学上可接受的盐。这些化合物具有5-HT4受体激动活性，因此对于哺乳动物，特别是人类的胃食管反流病、非溃疡性消化不良、功能性消化不良、肠易激综合征等的治疗是有用的。