(R)-4-(2-(2-(2-methylpyrrolidin-1-yl)ethyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)benzoic acid | 1131223-85-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (R)-4-(2-(2-(2-methylpyrrolidin-1-yl)ethyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)benzoic acid
• 英文别名: 4-[2-[2-[(2R)-2-methylpyrrolidin-1-yl]ethyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]benzoic acid
• CAS: 1131223-85-2
• 化学式: C₂₃H₂₆N₂O₃
• 分子量: 378.471
• InChiKey: MXRTWAZUXNCTKW-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-4-(2-(2-(2-methylpyrrolidin-1-yl)ethyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)benzoic acid 在 氯化亚砜 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 N-methyl-4-(2-{2-[(2R)-2-methylpyrrolidin-1-yl]ethyl}-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)benzamide hydrochloride
  参考文献：
  名称：

  2-(Pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(2H)-one Derivatives as Potent and Selective Histamine-3 Receptor Antagonists

  摘要：

  On the basis of the previously reported benzimidazole 1,3'-bipyrrolidine benzamides (1), a new class of 2-(pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(2H)-one derivatives (3-50) were synthesized and evaluated as potent H-3 receptor antagonists. In particular, compound 39 exhibited potent in vitro binding and functional activities at the H-3 receptor, good selectivities against other neurotransmitter receptors and ion channels, acceptable pharmacokinetic properties, and a favorable in vivo profile.

  DOI：

  10.1021/jm300011d
• 作为产物：
  描述：

  2-allyl-6-bromo-3,4-dihydroisoquinolin-1-one 在 sodium periodate 、 二氯双(三邻甲苯膦)合钯(II) 、 水 、 sodium cyanoborohydride 、 potassium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 水 为溶剂， 反应 11.67h， 生成 (R)-4-(2-(2-(2-methylpyrrolidin-1-yl)ethyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)benzoic acid
  参考文献：
  名称：

  2-(Pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(2H)-one Derivatives as Potent and Selective Histamine-3 Receptor Antagonists

  摘要：

  On the basis of the previously reported benzimidazole 1,3'-bipyrrolidine benzamides (1), a new class of 2-(pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(2H)-one derivatives (3-50) were synthesized and evaluated as potent H-3 receptor antagonists. In particular, compound 39 exhibited potent in vitro binding and functional activities at the H-3 receptor, good selectivities against other neurotransmitter receptors and ion channels, acceptable pharmacokinetic properties, and a favorable in vivo profile.

  DOI：

  10.1021/jm300011d

文献信息

• ISOQUINOLINYL AND ISOINDOLINYL DERIVATIVES AS HISTAMINE-3 ANTAGONISTS
  申请人：Zhou Dahui

  公开号：US20090069300A1

  公开（公告）日：2009-03-12

  The present invention provides a compound of formula I and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor.

  本发明提供了一种公式I的化合物及其用于治疗与组胺-3受体相关或受其影响的中枢神经系统疾病的应用。
• [EN] ISOQUINOLINYL AND ISOINDOLINYL DERIVATIVES AS HISTAMINE-3 ANTAGONISTS<br/>[FR] DÉRIVÉS D'ISOQUINOLINYLE ET D'ISOINDOLINYLE CONVENANT COMME ANTAGONISTES DE L'HISTAMINE-3
  申请人：WYETH CORP

  公开号：WO2009036144A1

  公开（公告）日：2009-03-19

  The present invention provides a compound of formula (I) and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor.
• 2-(Pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(<i>2H</i>)-one Derivatives as Potent and Selective Histamine-3 Receptor Antagonists
  作者：Dahui Zhou、Jonathan L. Gross、Adedayo B. Adedoyin、Suzan B. Aschmies、Julie Brennan、Mark Bowlby、Li Di、Katie Kubek、Brian J. Platt、Zheng Wang、Guoming Zhang、Nicholas Brandon、Thomas A. Comery、Albert J. Robichaud

  DOI：10.1021/jm300011d

  日期：2012.3.8

  On the basis of the previously reported benzimidazole 1,3'-bipyrrolidine benzamides (1), a new class of 2-(pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(2H)-one derivatives (3-50) were synthesized and evaluated as potent H-3 receptor antagonists. In particular, compound 39 exhibited potent in vitro binding and functional activities at the H-3 receptor, good selectivities against other neurotransmitter receptors and ion channels, acceptable pharmacokinetic properties, and a favorable in vivo profile.