Synthesis, benzodiazepine receptor affinity and anticonvulsant activity of 5-H-indeno[1,2-c]pyridazine derivatives.
Title compounds 1-36 were synthesized by reacting hydrazine with aldol adducts obtained from ninhydrin and methyl or alpha methylene ketones and aldehydes. Some of them showed a low, but significant benzodiazepine receptor affinity whose variation was interpreted through a structure-activity relationships study based on qualitative correlations and Comparative Molecular Field Analysis (CoMFA). Some indeno-pyridazine derivatives were found to possess an interesting anticonvulsant activity which however does not seem simply related to the benzodiazepine receptor modulation.
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Dipartimento Farmacochimico, Università degli Studi di Bari.
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Cellamare
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Carotti
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Genchi
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De Sarro
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D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D007192:Indenes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D011724:Pyridazines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D007192:Indenes; D011724:Pyridazines; D011963:Receptors, GABA-A