CONDENSATION OF MUSCIMOL OR THIOMUSCIMOL WITH AMINOPYRIDAZINES YIELDS GABA-A ANTAGONISTS

被引：41
|
作者：
MELIKIAN, A
SCHLEWER, G
CHAMBON, JP
WERMUTH, CG
机构：
[1] LAB PHARMACOCHIM MOLEC,CNRS,CTR NEUROCHIM,5 RUE BLASIE PASCAL,F-67084 STRASBOURG,FRANCE
[2] SANOFI RECH,F-34184 MONTPELLIER 04,FRANCE
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 22期
关键词：
D O I：
10.1021/jm00100a015
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Ten analogs of muscimol and thiomuscimol in which the amino function was delocalized in an amidinic system were prepared by N2 alkylation of 6-aryl-3-aminopyridazines with (chloromethyl) isoxazole or (chloromethyl)isothiazole derivatives. These muscimol and thiomuscimol derivatives show potent binding properties for GABA-A receptors (they displace [H-3]GABA and [H-3]gabazine) and provoke convulsions after iv injections. They fit well with the model pharmacophore proposed by our group for the GABA-A antagonists and show similar structure-activity profiles to that of the pyridazinyl-GABAs.
引用
收藏
页码：4092 / 4097
页数：6
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