3-{4-[(3-chloropropyl)oxy]phenyl}-2-methyl-4-(3H)-quinazolinone | 1044749-56-5

• 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-chloropropyl)oxy]phenyl}-2-methyl-4-(3H)-quinazolinone
• CAS: 1044749-56-5
• 化学式: C₁₈H₁₇ClN₂O₂
• 分子量: 328.798
• InChiKey: FYRWWXZGRVXAIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  44.12
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  七亚甲基亚胺 、 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， 以55%的产率得到3-(4-{[3-(1-azocanyl)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
• 作为产物：
  描述：

  1-(2-甲基-4-氧代-4H-喹唑啉-3-基)-4-羟基苯 、 1-溴-3-氯丙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以85%的产率得到3-{4-[(3-chloropropyl)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