SYNTHESIS OF 2',3'-DIDEOXY AND 3'-AZIDO-2',3'-DIDEOXYPYRIDAZINE NUCLEOSIDES AS POTENTIAL ANTIVIRAL AGENTS

The synthesis of 4-methoxy-, 4-amino-3-chloro-, and eoxy-beta-D-glycer o-pentofuranosyl)pyridazin-6-one nucleosides, 6, 19 and 20 is describe d. The synthesis of 3,4-dichloropyridazin-6-one (10) was accomplished in 44% overall yield using bromomaleic anhydride (17) as the starting material. The condensation of the silylated base of 10 with the haloge nose 12 in the presence of trimethylsilyl triflate as a catalyst affor ded a mixture of eoxy-beta-D-erythro-pentofuranosyl)pyridazin-6-one (1 3) in 67% and its alpha-anomer 14 in 12% yield, (r)espectively. A seri es of 3'-sulfonate esters were prepared to explore the synthesis of 3- chloro-4-hydroxy-1- eoxy-beta-D-erythro-pentofuranosyl)pyridazin-6-one (32) via 6,3-anhydronucleoside analogues. Compounds 15, 19 and 20 wer e evaluated against human immunodeficiency virus, human cytomegaloviru s, and herpes simplex virus type 1 but were inactive.