4-[(4-chlorophenyl)methyl]-2-{[(2S)-2-pyrrolidinyl]methyl}-1(2H)-phthalazinone | 955359-81-6

• 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)-2-pyrrolidinyl]methyl}-1(2H)-phthalazinone
• 英文别名: 4-(4-chlorobenzyl)-2-(pyrrolidin-2-ylmethyl)phthalazin-1(2H)-one；4-[(4-chlorophenyl)methyl]-2-[(2S)-2-pyrrolidinylmethyl]-1(2H)-phthalazinone；4-[(4-chlorophenyl)methyl]-2-[[(2S)-pyrrolidin-2-yl]methyl]phthalazin-1-one
• CAS: 955359-81-6
• 化学式: C₂₀H₂₀ClN₃O
• 分子量: 353.851
• InChiKey: QQYIEGRYADBWBV-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  44.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[(4-chlorophenyl)methyl]-2-{[(2S)-2-pyrrolidinyl]methyl}-1(2H)-phthalazinone 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 丁酮 为溶剂， 反应 115.25h， 生成 2-((1-(2-aminoethyl)pyrrolidin-2-yl)methyl)-4-(4-chlorobenzyl)phthalazin-1(2H)-one
  参考文献：
  名称：

  Design of Phthalazinone Amide Histamine H₁ Receptor Antagonists for Use in Rhinitis

  摘要：

  The synthesis of potent amide-containing phthalazinone H-1 histamine receptor antagonists is described. Three analogues 3e, 3g, and 9g were equipotent with azelastine and were longer-acting in vitro. Amide 3g had low oral bioavailability, low brain-penetration, high metabolic clearance, and long duration of action in vivo, and it was suitable for once-daily dosing intranasally, with a predicted dose for humans of approximately 0.5 mg per day.

  DOI：

  10.1021/acsmedchemlett.7b00112
• 作为产物：
  描述：

  4-(4-氯苄基)-1-(2H)-酞嗪酮 在 盐酸 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 4-[(4-chlorophenyl)methyl]-2-{[(2S)-2-pyrrolidinyl]methyl}-1(2H)-phthalazinone
  参考文献：
  名称：

  The Discovery of Phthalazinone-Based Human H₁ and H₃ Single-Ligand Antagonists Suitable for Intranasal Administration for the Treatment of Allergic Rhinitis

  摘要：

  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.

  DOI：

  10.1021/jm1013874

文献信息

• [EN] PHTHALAZINE AND PYRIDO [3,4-D] PYRIDAZ INE COMPOUNDS AS H1 RECEPTOR ANTAGONISTS<br/>[FR] PHTHALAZINE ET COMPOSÉS PYRIDO-[3,4-D]PYRIDAZINE COMME ANTAGONISTES DU RÉCEPTEUR H1
  申请人：GLAXO GROUP LTD

  公开号：WO2009047336A1

  公开（公告）日：2009-04-16

  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 diseases, such as allergic rhinitis.

  本发明涉及式(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）中的用途。
• 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。
• PHTHALAZINE AND PYRIDO[3,4-D]PYRIDAZINE COMPOUNDS AS H1 RECEPTOR ANTAGONISTS
  申请人：Gore Paul Martin

  公开号：US20100216799A1

  公开（公告）日：2010-08-26

  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 diseases, 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（例如过敏性鼻炎）中的使用。
• WO2007/122156
  申请人：——

  公开号：——

  公开（公告）日：——