Abstract |
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 [3H]GABA and [3H]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.
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Authors | A Melikian, G Schlewer, J P Chambon, C G Wermuth |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 35
Issue 22
Pg. 4092-7
(Oct 30 1992)
ISSN: 0022-2623 [Print] United States |
PMID | 1331456
(Publication Type: Journal Article)
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Chemical References |
- Convulsants
- GABA-A Receptor Antagonists
- Pyridazines
- Receptors, GABA-A
- Muscimol
- thiomuscimol
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Topics |
- Animals
- Binding, Competitive
- Convulsants
(chemical synthesis)
- Female
- GABA-A Receptor Antagonists
- In Vitro Techniques
- Mice
- Models, Molecular
- Molecular Conformation
- Muscimol
(analogs & derivatives, chemical synthesis, metabolism, pharmacology)
- Pyridazines
(chemical synthesis, metabolism, pharmacology)
- Radioligand Assay
- Rats
- Receptors, GABA-A
(metabolism)
- Structure-Activity Relationship
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