[Studies on synthesis, anticonvulsant activity and the structure--activity relationships of 6-(substituted phenyl)-3 (2H) pyridazinones].
In searching for effective anticonvulsant agent fourteen 6-(substituted-phenyl)-4,5-dihydro-3 (2H) pyridazinones and fifteen 6-(substitutedphenyl)-3 (2H) pyridazinones have been synthesized and screened in mice for their ability to antagonize maximal electroshock seizure (MES). The ED50 values showed that 6-(2',4'-dichlorophenyl)-3 (2H) pyridazinone was the most potent anticonvulsant in these compounds. The structure--activity relationships in these two series were examined. We came to the conclusion that the higher is the hydrophobic parameter pi of the substituent on phenyl ring, the more potent anticonvulsant is the compound. And also, only the compounds with an electronwithdrawing substituent on the phenyl ring exhibited appreciable anticonvulsant activity.
Xu
P
P
Department of Medicinal Chemistry, Beijing Medical University.
Wang
S Y
SY
Chen
Y
Y
Liu
W Q
WQ
Tao
C
C
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D011724:Pyridazines