[Studies on synthesis and anticonvulsant activity of 3-GABA derivatives of 6-(substituted-phenyl) pyridazines].
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).
Xu
P
P
Department of Medicinal Chemistry, Beijing Medical University.
Wang
S Y
SY
Liu
W Q
WQ
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D011724:Pyridazines / Q000737:chemistry* / Q000494:pharmacology
D000927:Anticonvulsants; D011724:Pyridazines