(R)-N-(2-(2-((4-(4-chlorobenzyl)-1-oxophthalazin-2(1H)-yl)methyl)pyrrolidin-1-yl)ethyl)-2,2,2-trifluoroacetamide | 1035040-47-1

• 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: (R)-N-(2-(2-((4-(4-chlorobenzyl)-1-oxophthalazin-2(1H)-yl)methyl)pyrrolidin-1-yl)ethyl)-2,2,2-trifluoroacetamide
• 英文别名: N-[2-((2R)-2-{[4-[(4-Chlorophenyl)methyl]-1-oxo-2(1H)-phthalazinyl]methyl}-1-pyrrolidinyl)ethyl]-2,2,2-trifluoroacetamide；N-[2-[(2R)-2-[[4-[(4-chlorophenyl)methyl]-1-oxophthalazin-2-yl]methyl]pyrrolidin-1-yl]ethyl]-2,2,2-trifluoroacetamide
• CAS: 1035040-47-1
• 化学式: C₂₄H₂₄ClF₃N₄O₂
• 分子量: 492.928
• InChiKey: GBSCUBRYBGFQFP-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-N-(2-(2-((4-(4-chlorobenzyl)-1-oxophthalazin-2(1H)-yl)methyl)pyrrolidin-1-yl)ethyl)-2,2,2-trifluoroacetamide 在 potassium carbonate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 (R)-4-(4-chlorobenzyl)-2-((1-(2-(methylamino)ethyl)pyrrolidin-2-yl)methyl)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：

  (R)-4-(4-chlorobenzyl)-2-(pyrrolidin-2-ylmethyl)phthalazin-1(2H)-one 、 N-(2-碘乙基)三氯乙酰胺 在 N,N-二异丙基乙胺 作用下， 以 丁酮 为溶剂， 以100%的产率得到(R)-N-(2-(2-((4-(4-chlorobenzyl)-1-oxophthalazin-2(1H)-yl)methyl)pyrrolidin-1-yl)ethyl)-2,2,2-trifluoroacetamide
  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

文献信息

• COMPOUNDS
  申请人：Gore Paul Martin

  公开号：US20100184770A1

  公开（公告）日：2010-07-22

  The present invention relates to a compound of formula (I) and salts thereof, process for preparation thereof, to compositions containing the same and to the use of such a compound in the treatment of various diseases, such as allergic rhinitis.

  本发明涉及一种式（I）化合物及其盐，其制备方法，含有该化合物的组合物，以及将该化合物用于治疗各种疾病，如过敏性鼻炎的用途。
• 4-BENZYL-1(2H)-PHTHALAZINONES AS H1 RECEPTOR ANTAGONISTS
  申请人：Glaxo Group Limited

  公开号：EP2091538B1

  公开（公告）日：2010-03-03
• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2008074803A2

  公开（公告）日：2008-06-26

  (EN) 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.(FR) La présente invention porte sur des composés de formule (I) et des sels de ceux-ci, sur des procédés permettant de les préparer, sur des compositions les contenant et sur leur utilisation dans le traitement de diverses maladies, telles que la rhinite allergique.
• Design of Phthalazinone Amide Histamine H₁ Receptor Antagonists for Use in Rhinitis
  作者：Panayiotis A. Procopiou、Alison J. Ford、Paul M. Gore、Brian E. Looker、Simon T. Hodgson、Duncan S. Holmes、Sadie Vile、Kenneth L. Clark、Ken A. Saunders、Robert J. Slack、James E. Rowedder、Clarissa J. Watts

  DOI：10.1021/acsmedchemlett.7b00112

  日期：2017.5.11

  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.