SYNTHESIS AND ANTICONVULSANT PROPERTIES OF TRIAZOLOPYRIDAZINYL AND IMIDAZOPYRIDAZINYL CARBOXAMIDES AND CARBOXYLIC-ACIDS

Analogues of -dichlorobenzyl)-6-methyltriazolo[4,3-b]pyridazine PC25 c ontaining amide or carboxylic acid function were synthesized and teste d for anticonvulsant activity. The compounds having the imidazole ring substituted with an amide group have been found to be generally more active against maximal electroshock-induced seizures in mice (15.2 les s than or equal to ED50 less than or equal to 37.5 mg kg(-1) orally). Furthermore, maximum activity was generally associated with a 2,6-dich lorobenzyl substitution pattern. -dichlorobenzyl)-6-methyltriazolo[4,3 -b]pyridazine 4b was also protective in the pentylenetetrazole-induced seizures test (ED50 = 91.1 mg kg(-1) orally) and blocked strychnine-i nduced tonic extensor seizures (ED50 = 62.9 mg kg(-1) orally). Moreove r, calculated electrostatic isopotential maps of the whole active comp ounds were quite similar and, consequently, could be associated to opt imum anticonvulsant activity. (C) 1998 Elsevier Science Ltd. All right s reserved.