Synthesis and anticonvulsant activity of novel 1-substituted-1,2-dihydro- pyridazine-3,6-diones

Abstract

The synthesis and pharmacological evaluation of novel 1-substituted-1,2- dihydro-pyridazine-3,6-diones (4a - l, 5a - j) as potential anticonvulsant agents are described. The compounds were tested in vivo for the anticonvulsant activity. The compound which have maximum protection against MES induced seizures is 1-[3-(2-aminophenylamino)-2-hydroxypropyl)-1,2-dihydro-pyridazine-3, 6-dione 4h (ED50=44.7mg·kg-1 i.p.) 1-[2-hydroxy-3-piperazin1-yl-propyl)-1,2-dihydro-pyridazine-3,6-dione 4c (ED50=72mg·kg-1 i.p.) and 1-[2-hydroxy-3-imidazol- 1-yl-propyl)-1,2-dihydro-pyridazine-3,6-dione 4d (ED50= 79mg·kg-1 i.p.) were also found to have maximum protection against MES induced seizures. Whereas all these compounds failed to protect the animals from subcutaneous pentylenetetrazole (Metrozol) seizure threshold test (sc-Met). © 2003 Pharmaceutical Society of Japan.