4-[(4-chlorophenyl)methyl]-2-{[(2S)-1-[4-[4-{3-(hexahydro-1H-azepin-1-yl)propoxy}phenyl]butyl]-2-pyrrolidinyl]methyl}-1(2H)-phthalazinone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-[(4-chlorophenyl)methyl]-2-{[(2S)-1-[4-[4-{3-(hexahydro-1H-azepin-1-yl)propoxy}phenyl]butyl]-2-pyrrolidinyl]methyl}-1(2H)-phthalazinone
• 英文别名: 4-[(4-chlorophenyl)methyl]-2-({(2S)-1-[4-(4-{[3-(hexahydro-1H-azepin-1-yl)propyl]oxy}phenyl)butyl]-2-pyrrolidinyl}methyl)-1(2H)-phthalazinone；2-[[(2S)-1-[4-[4-[3-(azepan-1-yl)propoxy]phenyl]butyl]pyrrolidin-2-yl]methyl]-4-[(4-chlorophenyl)methyl]phthalazin-1-one
• 化学式: C₃₉H₄₉ClN₄O₂
• 分子量: 641.297
• InChiKey: YANGEESWIGIKOP-UMSFTDKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.3
• 重原子数：
  46
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-[(4-chlorophenyl)methyl]-2-{[(2S)-2-pyrrolidinyl]methyl}-1(2H)-phthalazinone 在 三溴化硼 、 potassium carbonate 、 potassium iodide 作用下， 以 二氯甲烷 、 丁酮 为溶剂， 反应 102.0h， 生成 4-[(4-chlorophenyl)methyl]-2-{[(2S)-1-[4-[4-{3-(hexahydro-1H-azepin-1-yl)propoxy}phenyl]butyl]-2-pyrrolidinyl]methyl}-1(2H)-phthalazinone
  参考文献：
  名称：

  WO2007/122156

  摘要：

  公开号：

文献信息

• COMPOUNDS
  申请人：GORE Martin Paul

  公开号：US20080039444A1

  公开（公告）日：2008-02-14

  The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders, such as allergic rhinitis.

  本发明涉及式(I)化合物及其盐，其制备过程，含有它们的组合物以及它们在治疗各种疾病（如过敏性鼻炎）中的用途。
• 2-Substituted 4-Benzylphthalazinone Derivatives as Histamine H1 and H3 Antagonists
  申请人：Gore Paul Martin

  公开号：US20090105225A1

  公开（公告）日：2009-04-23

  The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders, such as allergic rhinitis.

  本发明涉及公式(I)的化合物及其盐，其制备方法，含有它们的组合物以及它们在治疗各种疾病，如过敏性鼻炎中的应用。
• WO2007/122156
  申请人：——

  公开号：——

  公开（公告）日：——
• 2-SUBSTITUTED 4-BENZYLPHTHALAZINONE DERIVATIVES AS HISTAMINE H1 AND H3 ANTAGONISTS
  申请人：Glaxo Group Limited

  公开号：EP2007735B1

  公开（公告）日：2010-10-27
• The Discovery of Phthalazinone-Based Human H₁ and H₃ Single-Ligand Antagonists Suitable for Intranasal Administration for the Treatment of Allergic Rhinitis
  作者：Panayiotis A. Procopiou、Christopher Browning、Jennifer M. Buckley、Kenneth L. Clark、Lise Fechner、Paul M. Gore、Ashley P. Hancock、Simon T. Hodgson、Duncan S. Holmes、Michael Kranz、Brian E. Looker、Karen M. L. Morriss、Daniel L. Parton、Linda J. Russell、Robert J. Slack、Steven L. Sollis、Sadie Vile、Clarissa J. Watts

  DOI：10.1021/jm1013874

  日期：2011.4.14

  A series of potent phthalazinone-based human H-1 and H-3 bivalent histamine receptor antagonists, suitable for intranasal administration for the potential treatment of allergic rhinitis, were identified. Blockade of H-3 receptors is thought to improve efficacy on nasal congestion, a symptom of allergic rhinitis that is currently not treated by current antihistamines. Two analogues (56a and 56b) had slightly lower H-1, potency (pA(2) 9.1 and 8.9, respectively, vs 9.7 for the clinical gold-standard azelastine, and H-3 potency (pK(i) 9.6 and 9.5, respectively, vs 6.8 for azelastine). Compound 56a had longer duration of action than azelastine, low brain penetration, and low oral bioavailability, which coupled with the predicted low clinical dose, should limit the potential of engaging CNS-related side-effects associated with H-1 or H-3 antagonism.