(R)-N-(2-(2-((4-(4-chlorobenzyl)-1-oxophthalazin-2(1H)-yl)methyl)pyrrolidin-1-yl)ethyl)-4-methoxy-N-methylbutanamide trifluoroacetate salt | 1035040-52-8

• 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)-4-methoxy-N-methylbutanamide trifluoroacetate salt
• 英文别名: N-[2-((2R)-2-{[4-[(4-Chlorophenyl)methyl]-1-oxo-2(1H)-phthalazinyl]methyl}-1-pyrrolidinyl)ethyl]-N-methyl-4-(methyloxy)butanamide, trifluoroacetate；N-[2-[(2R)-2-[[4-[(4-chlorophenyl)methyl]-1-oxophthalazin-2-yl]methyl]pyrrolidin-1-yl]ethyl]-4-methoxy-N-methylbutanamide;2,2,2-trifluoroacetic acid
• CAS: 1035040-52-8
• 化学式: C₂HF₃O₂*C₂₈H₃₅ClN₄O₃
• 分子量: 625.088
• InChiKey: FKEYBQUXJBIQQC-GNAFDRTKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.62
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (R)-4-(4-chlorobenzyl)-2-(pyrrolidin-2-ylmethyl)phthalazin-1(2H)-one 在 potassium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 丁酮 为溶剂， 反应 31.0h， 生成 (R)-N-(2-(2-((4-(4-chlorobenzyl)-1-oxophthalazin-2(1H)-yl)methyl)pyrrolidin-1-yl)ethyl)-4-methoxy-N-methylbutanamide trifluoroacetate salt
  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

• 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.