3-(4-{[3-(3,5-dimethyl-1-piperidinyl)propyl]oxy}phenyl)-2-methyl-4(3H)-quinazolinone | 1044749-58-7

• 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: 3-(4-{[3-(3,5-dimethyl-1-piperidinyl)propyl]oxy}phenyl)-2-methyl-4(3H)-quinazolinone
• 英文别名: 3-[4-[3-[(3R,5S)-3,5-dimethylpiperidin-1-yl]propoxy]phenyl]-2-methylquinazolin-4-one
• CAS: 1044749-58-7
• 化学式: C₂₅H₃₁N₃O₂
• 分子量: 405.54
• InChiKey: ZTESOUAADVEJOU-KDURUIRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  45.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,5-二甲基哌啶 、 3-{4-[(3-chloropropyl)oxy]phenyl}-2-methyl-4-(3H)-quinazolinone 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-(4-{[3-(3,5-dimethyl-1-piperidinyl)propyl]oxy}phenyl)-2-methyl-4(3H)-quinazolinone 、 3-(4-{[3-(3,5-dimethyl-1-piperidinyl)propyl]oxy}phenyl)-2-methyl-4(3H)-quinazolinone
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships, and Biological Profiles of a Quinazolinone Class of Histamine H₃ Receptor Inverse Agonists

  摘要：

  A new series of quinazolinone derivatives was synthesized and evaluated as nonimidazole H(3) receptor inverse agonists. 2-Methyl-3-(4-{[3-(1-pyrrolidinyl)propy]oxy}phenyl)-5-(trifluoromethyl)-4(3H)-quinazolinone (1) was identified as a promising derivative for further evaluation following optimization of key parameters. Compound 1 has potent H3 inverse agonist activity and excellent selectivity over other histamine receptor subtypes and a panel of 115 unrelated diverse binding sites. Compound 1 also shows satisfactory pharmacokinetic profiles and brain penetrability in laboratory animals. Two hours after oral administration of 30 mg/kg of 1 to SD rats, significant elevation of brain histamine levels was observed where the brain H3 receptor was highly occupied (>90%). On the basis of species differences in P-glycoprotein (P-gp) susceptibility of I between human and rodent P-gps, the observed rodent brain permeability of I is significantly limited by P-gp mediated efflux in rodents, whereas the extent of P-gp mediated efflux in humans should be very small or negligible. The potential of 1 to be an efficacious drug was demonstrated by its excellent brain penetrability and receptor occupancy in P-gp-deficient CF-1 mice.

  DOI：

  10.1021/jm8003834