3-(4-piperidin-4-yloxyphenyl)-4,5-dihydro-1H-pyridazin-6-one | 1005403-42-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(4-piperidin-4-yloxyphenyl)-4,5-dihydro-1H-pyridazin-6-one
• CAS: 1005403-42-8
• 化学式: C₁₅H₁₉N₃O₂
• 分子量: 273.335
• InChiKey: VFGUJYHYYNDPET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  62.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-piperidin-4-yloxyphenyl)-4,5-dihydro-1H-pyridazin-6-one 在 sodium cyanoborohydride 、 caesium carbonate 作用下， 以 甲醇 、 溶剂黄146 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-[4-(1-cyclobutyl-piperidin-4-yloxy)-phenyl]-2H-pyridazin-3-one
  参考文献：
  名称：

  4-Phenoxypiperidine pyridazin-3-one histamine H3 receptor inverse agonists demonstrating potent and robust wake promoting activity

  摘要：

  Structure-activity relationships for a series of phenoxypiperidine pyridazin-3-one H3R antagonists/inverse agonists are disclosed. The search for compounds with improved hERG and DAT selectivity without the formation of in vivo active metabolites identified 6-[4-(1-cyclobutyl-piperidin-4-yloxy)phenyl]- 4,4-dimethyl-4,5-dihydro-2H-pyridazin-3-one 17b. Compound 17b met discovery flow criteria, demonstrated potent H3R functional antagonism in vivo in the rat dipsogenia model and potent wake activity in the rat EEG/EMG model at doses as low as 0.1 mg/kg ip. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.026
• 作为产物：
  描述：

  4-(4-羟基苯基)-4-氧代丁酸乙酯 在 三苯基膦 、 三氟乙酸 、 肼 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 异丙醇 为溶剂， 生成 3-(4-piperidin-4-yloxyphenyl)-4,5-dihydro-1H-pyridazin-6-one
  参考文献：
  名称：

  4-Phenoxypiperidine pyridazin-3-one histamine H3 receptor inverse agonists demonstrating potent and robust wake promoting activity

  摘要：

  Structure-activity relationships for a series of phenoxypiperidine pyridazin-3-one H3R antagonists/inverse agonists are disclosed. The search for compounds with improved hERG and DAT selectivity without the formation of in vivo active metabolites identified 6-[4-(1-cyclobutyl-piperidin-4-yloxy)phenyl]- 4,4-dimethyl-4,5-dihydro-2H-pyridazin-3-one 17b. Compound 17b met discovery flow criteria, demonstrated potent H3R functional antagonism in vivo in the rat dipsogenia model and potent wake activity in the rat EEG/EMG model at doses as low as 0.1 mg/kg ip. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.026

文献信息

• Pyridizinone Derivatives
  申请人：Cephalon, Inc.

  公开号：EP2492263A1

  公开（公告）日：2012-08-29

  The present invention provides compounds of formula (I*): their use as H3 inhibitors, 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 抑制剂的用途、制备工艺及其药物组合物。
• PYRIDIZINONE DERIVATIVES
  申请人：Cephalon, Inc.

  公开号：EP2069312B1

  公开（公告）日：2012-11-07
• [EN] PYRIDIZINONE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRIDIZINONE
  申请人：CEPHALON INC

  公开号：WO2008013838A2

  公开（公告）日：2008-01-31

  [EN] The present invention provides compounds of formula (I*): their use as H₃ inhibitors, processes for their preparation, and pharmaceutical compositions thereof.
  [FR] La présente invention concerne des composés représentés par la formule (I*): leur utilisation comme inhibiteurs de H₃, des procédés permettant de les préparer et des compositions pharmaceutiques les contenant.
• 4-Phenoxypiperidine pyridazin-3-one histamine H3 receptor inverse agonists demonstrating potent and robust wake promoting activity
  作者：Robert L. Hudkins、Allison L. Zulli、Reddeppa reddy Dandu、Ming Tao、Kurt A. Josef、Lisa D. Aimone、R. Curtis Haltiwanger、Zeqi Huang、Jacquelyn A. Lyons、Joanne R. Mathiasen、Rita Raddatz、John A. Gruner

  DOI：10.1016/j.bmcl.2012.01.026

  日期：2012.2

  Structure-activity relationships for a series of phenoxypiperidine pyridazin-3-one H3R antagonists/inverse agonists are disclosed. The search for compounds with improved hERG and DAT selectivity without the formation of in vivo active metabolites identified 6-[4-(1-cyclobutyl-piperidin-4-yloxy)phenyl]- 4,4-dimethyl-4,5-dihydro-2H-pyridazin-3-one 17b. Compound 17b met discovery flow criteria, demonstrated potent H3R functional antagonism in vivo in the rat dipsogenia model and potent wake activity in the rat EEG/EMG model at doses as low as 0.1 mg/kg ip. (C) 2012 Elsevier Ltd. All rights reserved.