[2-Benzyl-5-[3-(dimethylamino)propoxy]pyrazol-3-yl]-morpholin-4-ylmethanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: [2-Benzyl-5-[3-(dimethylamino)propoxy]pyrazol-3-yl]-morpholin-4-ylmethanone
• 化学式: C₂₀H₂₈N₄O₃
• 分子量: 372.467
• InChiKey: GZJONBGCSHHPLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  59.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-二甲氨基-1-丙醇 在 sodium hydroxide 、 三丁基膦 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 甲苯 为溶剂， 反应 2.0h， 生成 [2-Benzyl-5-[3-(dimethylamino)propoxy]pyrazol-3-yl]-morpholin-4-ylmethanone
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Pyrazoles and Indazoles as Activators of the Nitric Oxide Receptor, Soluble Guanylate Cyclase

  摘要：

  Database searching and compound screening identified 1-benzyl-3-(3-dimethylaminopropyloxy)-indazole (benzydamine, 3) as a potent activator of the nitric oxide receptor, soluble guanylate cyclase. A comprehensive structure-activity relationship study surrounding 3 clearly showed that the indazole C-3 dimethylaminopropyloxy substituent was critical for enzyme activity. However replacement of the indazole ring of 3 by appropriately substituted pyrazoles maintained enzyme activity. Compounds were evaluated for inhibition of platelet aggregation and showed a general lipophilicity requirement. Aryl-substituted pyrazoles 32, 34, and 43 demonstrated potent activation of soluble guanylate cyclase and potent inhibition of platelet aggregation. Pharmacokinetic studies in rats showed that compound 32 exhibits modest oral bioavailability (12%). Furthermore 32 has an excellent selectivity profile notably showing no significant inhibition of phosphodiesterases or nitric oxide synthases.

  DOI：

  10.1021/jm001034k