3-(4,4-diphenylsemicarbazido)-5-benzyl-6-methylpyridazine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(4,4-diphenylsemicarbazido)-5-benzyl-6-methylpyridazine
• 英文别名: 3-[(5-Benzyl-6-methylpyridazin-3-yl)amino]-1,1-diphenylurea
• 化学式: C₂₅H₂₃N₅O
• 分子量: 409.491
• InChiKey: YJBXLAPJNGALSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  70.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  二苯氨基甲酰氯 、 3-hydrazino-5-benzyl-6-methylpyridazine 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 24.0h， 以15%的产率得到3-(4,4-diphenylsemicarbazido)-5-benzyl-6-methylpyridazine
  参考文献：
  名称：

  Synthesis and Anticonvulsant Properties of New Benzylpyridazine Derivatives

  摘要：

  Several 3-substituted pyridazines and a series of imidazo- and triazolopyridazines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures in mice. The most active derivatives, 3-ureidopyridazine 7 and triazolopyridazines 16, 18, 21, and 25 with oral ED(50)'s that ranged from 6.2 to 22.0 mg/kg, were more extensively investigated by evaluating their ability to prevent chemically induced seizures and were compared with phenytoin, phenobarbital, sodium valproate, carbamazepine, and diazepam. 3-amino-7-(2,6-dichlorobenzyl)-6-methyltriazolo-[4,3-b]pyridazine (25) was also protective in the pentylenetetrazole-induced seizures test (ED(50) 76 mg/kg per os) and blocked strychnine-induced tonic extensor seizures (ED(50) = 34.5 mg/kg per os). Furthermore, derivative 25 showed anticonvulsant effects on bicuculline- and yohimbine-induced seizures tests in mice. All these results suggest that the pharmacological activity of 25 is partly due to modifications of glycinergic and GABAergic transmission. Moreover, molecular modeling studies based on the antiepileptic drug lamotrigine and the most stable conformer of 25 show structural similarities between these two molecules. This conformer also agrees with the electronic tolerances and volume of benzodiazepine pharmacophore models.

  DOI：

  10.1021/jm00040a006

文献信息

• Moreau Stephane, Coudert Pascal, Rubat Catherine, Gardette Daniel, Vallee+, J. Med. Chem, 37 (1994) N 14, S 2153-2160
  作者：Moreau Stephane, Coudert Pascal, Rubat Catherine, Gardette Daniel, Vallee+

  DOI：——

  日期：——
• Synthesis and Anticonvulsant Properties of New Benzylpyridazine Derivatives
  作者：Stephane Moreau、Pascal Coudert、Catherine Rubat、Daniel Gardette、Danielle Vallee-Goyet、Jacques Couquelet、Pierre Bastide、Pierre Tronche

  DOI：10.1021/jm00040a006

  日期：1994.7

  Several 3-substituted pyridazines and a series of imidazo- and triazolopyridazines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures in mice. The most active derivatives, 3-ureidopyridazine 7 and triazolopyridazines 16, 18, 21, and 25 with oral ED(50)'s that ranged from 6.2 to 22.0 mg/kg, were more extensively investigated by evaluating their ability to prevent chemically induced seizures and were compared with phenytoin, phenobarbital, sodium valproate, carbamazepine, and diazepam. 3-amino-7-(2,6-dichlorobenzyl)-6-methyltriazolo-[4,3-b]pyridazine (25) was also protective in the pentylenetetrazole-induced seizures test (ED(50) 76 mg/kg per os) and blocked strychnine-induced tonic extensor seizures (ED(50) = 34.5 mg/kg per os). Furthermore, derivative 25 showed anticonvulsant effects on bicuculline- and yohimbine-induced seizures tests in mice. All these results suggest that the pharmacological activity of 25 is partly due to modifications of glycinergic and GABAergic transmission. Moreover, molecular modeling studies based on the antiepileptic drug lamotrigine and the most stable conformer of 25 show structural similarities between these two molecules. This conformer also agrees with the electronic tolerances and volume of benzodiazepine pharmacophore models.