10-((2-Fluoro-4-pyridinyl)methyl)-10-(4-pyridinylmethyl)-9(10H)-anthracenone

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 10-((2-Fluoro-4-pyridinyl)methyl)-10-(4-pyridinylmethyl)-9(10H)-anthracenone
• 英文别名: 10-[(2-Fluoropyridin-4-yl)methyl]-10-(pyridin-4-ylmethyl)anthracen-9-one
• 化学式: C₂₆H₁₉FN₂O
• 分子量: 394.448
• InChiKey: MOSJFJVURUGZBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  42.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氟-4-甲基吡啶 在 sodium hydroxide 、 N-氯代丁二酰亚胺 、 过氧化氢苯甲酰 、 苄基三乙基氯化铵 作用下， 以 四氯化碳 、 甲苯 为溶剂， 反应 76.0h， 生成 10-((2-Fluoro-4-pyridinyl)methyl)-10-(4-pyridinylmethyl)-9(10H)-anthracenone
  参考文献：
  名称：

  2-Fluoro-4-pyridinylmethyl Analogues of Linopirdine as Orally Active Acetylcholine Release-Enhancing Agents with Good Efficacy and Duration of Action

  摘要：

  In an effort to improve the pharmacokinetic and pharmacodynamic properties of the cognition-enhancer linopirdine (DuP 996), a number of core structure analogues were prepared in which the 4-pyridyl pendant group was systematically replaced with 2-fluoro-4-pyridyl. This strategy resulted in the discovery of several compounds with improved activity in acetylcholine (ACh) release-enhancing assays, in vitro and in vivo. The most effective compound resulting from these studies, 10,10-bis[(2-fluoro-4-pyridinyl)methyl]-9(10H)-anthracenone (9), is between 10 and 20 times more potent than linopirdine in increasing extracellular hippocampal ACh levels in the rat with a minimum effective dose of 1 mg/kg. In addition to superior potency, 9 possesses an improved pharmacokinetic profile compared to that of linopirdine. The half-life of 9 (2 h) in rats is 4-fold greater than that of linopirdine (0.5 h), and it showed a g-fold improvement in brain-plasma distribution over linopirdine. On the basis of its pharmacologic, pharmacokinetic, absorption, and distribution properties, 9 (DMP543) has been advanced for clinical evaluation as a potential palliative therapeutic for treatment of Alzheimer's disease.

  DOI：

  10.1021/jm9803424

文献信息

• US5594001A
  申请人：——

  公开号：US5594001A

  公开（公告）日：1997-01-14
• US5750528A
  申请人：——

  公开号：US5750528A

  公开（公告）日：1998-05-12
• US5990132A
  申请人：——

  公开号：US5990132A

  公开（公告）日：1999-11-23
• US6262081B1
  申请人：——

  公开号：US6262081B1

  公开（公告）日：2001-07-17
• [EN] NOVEL POLYCYCLIC SYSTEMS, AND DERIVATIVES THEREOF, AS NEUROTRANSMITTER RELEASE ENHANCER USEFUL IN THE TREATMENT OF COGNITIVE DISORDERS<br/>[FR] NOUVEAUX SYSTEMES POLYCYCLIQUES ET LEURS DERIVES SERVANT D'ACTIVATEURS DE LA LIBERATION DE NEUROTRANSMETTEURS, UTILISES DANS LE TRAITEMENT DE TROUBLES COGNITIFS
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：WO1994024131A1

  公开（公告）日：1994-10-27

  (EN) Compounds of formula (I) have been shown to enhance the release of the neurotransmitter acetylcholine, and thus may be useful in the treatment of diseases of man where subnormal levels of this neurochemical are found, such as in Alzheimer's disease, and other conditions involving learning and cognition. This invention describes compounds, pharmaceutical compositions and methods of treatment comprising compounds of formula (I).(FR) On a mis en évidence que les composés de la formule (I) permettent d'activer la libération du neurotransmetteur acétylcholine, et par conséquent, peuvent être utiles dans le traitement de maladies chez des sujets présentant des niveaux subnormaux de cette substance neurochimique, tel que dans la maladie d'Alzheimer et dans d'autres états impliquant l'apprentissage et la cognition. Cette invention concerne des composés, des compositions pharmaceutiques et des procédés de traitement comprenant les composés de la formule (I).