2-[4-(furan-2-carbonyl)-piperazin-1-yl]-1-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-ethanone | 1260098-48-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[4-(furan-2-carbonyl)-piperazin-1-yl]-1-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-ethanone
• 英文别名: 2-[4-(furan-2-carbonyl)piperazin-1-yl]-1-[4-[3-[(2R)-2-methylpyrrolidin-1-yl]propoxy]phenyl]ethanone
• CAS: 1260098-48-3
• 化学式: C₂₅H₃₃N₃O₄
• 分子量: 439.555
• InChiKey: TXUQRJZCUVIQAO-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  66.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  呋喃甲酰氯 在 盐酸 、 水 、 potassium carbonate 、 三乙胺 、 sodium iodide 作用下， 以 二氯甲烷 、 乙腈 、 丁酮 为溶剂， 生成 2-[4-(furan-2-carbonyl)-piperazin-1-yl]-1-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-ethanone
  参考文献：
  名称：

  Substituted phenoxypropyl-(R)-2-methylpyrrolidine aminomethyl ketones as histamine-3 receptor inverse agonists

  摘要：

  Optimization of a series of aminomethyl ketone diamine H3R antagonists to reduce the brain exposure by lowering the pKa, led to molecules with improved pharmacokinetic properties. Compounds 9, 19, and 25 had high affinity for human H3R and demonstrated in vivo H3R functional activity in the rat dipsogenia model. Compound 9 displayed modest wake-promoting activity in the rat EEG/EMG model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.081

文献信息

• [EN] SUBSTITUTED PHENOXYPROPYLCYCLOAMINE DERIVATIVES AS HISTAMINE-3 (H3) RECEPTOR LIGANDS<br/>[FR] DÉRIVÉS DE PHÉNOXYPROPYLCYCLOAMINE SUBSTITUÉS EN TANT QUE LIGANDS DE RÉCEPTEUR D'HISTAMINE-3 (H3)
  申请人：CEPHALON INC

  公开号：WO2011002984A1

  公开（公告）日：2011-01-06

  The present invention provides compounds of formula I: their use as H3 antagonists/inverse agonists, processes for their preparation, and pharmaceutical compositions thereof.

  本发明提供了式I的化合物：它们作为H3受体拮抗剂/逆向激动剂的用途，它们的制备方法以及药物组合物。
• Substituted Phenoxypropylcycloamine Derivatives as Histamine-3 (H3) Receptor Ligands
  申请人：Bacon Edward R.

  公开号：US20120238551A1

  公开（公告）日：2012-09-20

  The present invention provides compounds of formula I: their use as H 3 antagonists/inverse agonists, processes for their preparation, and pharmaceutical compositions thereof.
• SUBSTITUTED PHENOXYPROPYLCYCLOAMINE DERIVATIVES AS HISTAMINE-3 (H3) RECEPTOR LIGANDS
  申请人：Bacon Edward R.

  公开号：US20140296212A1

  公开（公告）日：2014-10-02

  The present invention provides compounds of formula I: their use as H 3 antagonists/inverse agonists, processes for their preparation, and pharmaceutical compositions thereof.
• US8648067B2
  申请人：——

  公开号：US8648067B2

  公开（公告）日：2014-02-11
• Substituted phenoxypropyl-(R)-2-methylpyrrolidine aminomethyl ketones as histamine-3 receptor inverse agonists
  作者：Allison L. Zulli、Lisa D. Aimone、Joanne R. Mathiasen、John A. Gruner、Rita Raddatz、Edward R. Bacon、Robert L. Hudkins

  DOI：10.1016/j.bmcl.2012.02.081

  日期：2012.4

  Optimization of a series of aminomethyl ketone diamine H3R antagonists to reduce the brain exposure by lowering the pKa, led to molecules with improved pharmacokinetic properties. Compounds 9, 19, and 25 had high affinity for human H3R and demonstrated in vivo H3R functional activity in the rat dipsogenia model. Compound 9 displayed modest wake-promoting activity in the rat EEG/EMG model. (C) 2012 Elsevier Ltd. All rights reserved.