7-(2-fluorobenzyl)-4-(substituted)-7H-imidazo[4,5-d]-1,2,3-triazines and -7H-pyrazolo[3,4-d]-1,2,3-triazines. Synthesis and anticonvulsant activity

Article abstract of DOI:10.1002/jhet.5570320502

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-methylamino-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.