7-(2-FLUOROBENZYL)-4-(SUBSTITUTED)-7H-IMIDAZO[4,5-D]-1,2,3-TRIAZINES AND 7-(2-FLUOROBENZYL)-4-(SUBSTITUTED)-7H-PYRAZOLO[3,4-D]-1,2,3-TRIAZINES - SYNTHESIS AND ANTICONVULSANT ACTIVITY

The imidazo[4,5-d]-1,2,3-triazine and pyrazolo[3,4-d]-1,2,3-triazine analogues of the potent anticonvulsant purine, BW 78U79 (9-(2-fluorobenzyl)-6-methylamine-9H-purine, 1), were synthesized and tested for anticonvulsant activity. The imidazo[4,5-d]-1,2,3-triazines 11-13 were prepared in four steps from 5-aminoimidazole-4-carboxamide (2) and the pyrazolo[3,4-d]-1,2,3-triazines 18-21 were synthesized starting with 5-amino-1-(2-fluorobenzyl)pyrazole-4-carbonitrile (14). The intermediate 1,2,3-triazin-4-ones 6 and 16 were converted to the 4-substituted targets via the 4-(4-dimethylaminopyridinium) salts 10 and 17. Imidazotriazine 11 had potent anticonvulsant activity against maximal electroshock-induced seizures, but its propensity to cause emesis precluded further development.