[Studies on synthesis and anticonvulsant activity of 3-GABA derivatives of 6-(substituted-phenyl) pyridazines].

Abstract

In recent years considerable emphasis has been placed on the hypothesis that enhancement of GABA transmission could be beneficial in some types of epilepsy. The alpha-(aryl)-4-morpholineacetonitrile obtained by the interaction of aryl aldehydes, morpholine and potassium cyanide, have been used to synthesize 3-(aroyl)-propionic acids and esters by 1,4-additions to acrylonitrile or acrylic ester. 3-(Aroyl) propionic acids reacting with hydrazine can yield 6-aryl-4,5-dihydro-3(2H) pyridazinones which are dehydrogenated by bromine (via bromination dehydrobromination) to give 6-aryl-3(2H) pyridazinones. The latter compounds were converted into 3-(N-GABA)-6-(substitutedphenyl) pyridazines and 3-(N-butyryllactamyl)-6-(substitutedphenyl) pyridazines by the chlorination (by means of phosphorus oxychloride) and then reaction with GABA. By this method seventeen 3-GABA derivatives of 6-(substituted-phenyl)pyridazines were synthesized. The anticonvulsant activity (MES) of these compounds were also tested. 3-(N-GABA)-6-(2',4'-dichloro)phenylpyridazine; potent anticonvulsant (ED50 = 21.05 mg/kg).

• Authors: P Xu, S Y Wang, W Q Liu
• Journal: Yao xue xue bao = Acta pharmaceutica Sinica (Yao Xue Xue Bao) Vol. 26 Issue 9 Pg. 650-5 ( 1991) ISSN: 0513-4870 [Print] China
• PMID: 1821083 (Publication Type: English Abstract, Journal Article)

Chemical References

• Anticonvulsants
• Pyridazines

Topics

• Animals
• Anticonvulsants (chemical synthesis, pharmacology)
• Male
• Mice
• Pyridazines (chemistry, pharmacology)