1-[4-(3-chloro-propoxy)-phenyl]-2-morpholin-4-yl-ethanone | 1260099-53-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[4-(3-chloro-propoxy)-phenyl]-2-morpholin-4-yl-ethanone
• 英文别名: 1-[4-(3-Chloropropoxy)phenyl]-2-morpholin-4-ylethanone
• CAS: 1260099-53-3
• 化学式: C₁₅H₂₀ClNO₃
• 分子量: 297.782
• InChiKey: PTYJGRYCTYEFNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[4-(3-chloro-propoxy)-phenyl]-2-morpholin-4-yl-ethanone 、 2-甲基吡咯烷 在 potassium carbonate 、 sodium iodide 作用下， 生成 1-{4-[3-(2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-2-morpholin-4-yl-ethanone
  参考文献：
  名称：

  [EN] SUBSTITUTED PHENOXYPROPYLCYCLOAMINE DERIVATIVES AS HISTAMINE-3 (H3) RECEPTOR LIGANDS
  [FR] DÉRIVÉS DE PHÉNOXYPROPYLCYCLOAMINE SUBSTITUÉS EN TANT QUE LIGANDS DE RÉCEPTEUR D'HISTAMINE-3 (H3)

  摘要：

  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。

  公开号：

  WO2011002984A1
• 作为产物：
  描述：

  1-[4-(3-chloropropoxy)phenyl]ethanone 在 溴 、 potassium carbonate 作用下， 以 乙醚 、 乙腈 为溶剂， 生成 1-[4-(3-chloro-propoxy)-phenyl]-2-morpholin-4-yl-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

• Novel morpholine ketone analogs as potent histamine H3 receptor inverse agonists with wake activity
  作者：Babu G. Sundar、Thomas R. Bailey、Derek Dunn、Greg A. Hostetler、Sankar Chatterjee、Edward R. Bacon、Christoph Yue、Dominique Schweizer、Lisa D. Aimone、John A. Gruner、Jacquelyn Lyons、Rita Raddatz、Brigitte Lesur

  DOI：10.1016/j.bmcl.2012.01.004

  日期：2012.2

  Structure-activity relationship on a novel ketone class of H3R antagonists/inverse agonists is disclosed. Compound 4 showed excellent target potency, selectivity and brain penetration. Evaluation of antagonist 4 in the rat EEG/EMG model demonstrated robust wake activity thereby establishing preclinical proof of concept. (C) 2012 Elsevier Ltd. All rights reserved.
• SUBSTITUTED PHENOXYPROPYLCYCLOAMINE DERIVATIVES AS HISTAMINE-3 (H3) RECEPTOR LIGANDS
  申请人：Cephalon, Inc.

  公开号：EP2459529A1

  公开（公告）日：2012-06-06
• 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.
• US8648067B2
  申请人：——

  公开号：US8648067B2

  公开（公告）日：2014-02-11
• [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。