Synthesis and Biological Activity of Pyridazinooxazines

4-Chloro-5-(2-hydroxyethylamino)-3 (2H)-pyridazinones were converted upon treatment with base to novel fused ring compounds, 3, 4-dihydro-2H-pyridazino [4, 5-b]-1, 4-oxazin-8 (7H)-ones. When a nitrogen atom in the hydroxyethylamino group or at the 2-position of the 3 (2H)-pyridazinone ring had a remaining hydrogen, the ring closure reaction did not occur. 3, 4-Dihydro-2H-pyridazino [4, 5-b]-1, 4-oxazine was similarly synthesized from corresponding precursor. The presence of a C-6 amino group in the precursor did not affect the ring formation mentioned above, but when the amino group was diazotized, ring formation took place in a different fashion, involving the C-6 diazonium moiety as a leaving group, to give another ring system, 6, 7-dihydro-2H-pyridazino [3, 4-b]-[1, 4] oxazin-3 (5H)-one. Similar phenomena were observed in the cases of precursors having a C-6 nitro group : cyclization occurred involving the elimination of the nitro group to give fused ring products. The method was applied to the formation of a tricyclic heterocycle, 2H-pyridazino [3, 4-b] [1, 4] benzoxazin-3 (5H)-one. Some compounds thus obtained were found to have potent analgesic and significant anti-inflammatory activities in animal models.