Pyridazine nucleoside analogs

In a synthesis of nucleoside analogs, the sodium salts of phthalazine-l,4-dione, phthalazin-l(2//)-one, and two pyridazin-3(2//)-ones, prepared with sodium hydride in DMF, were alkylated with ( )-2,3-0-isopropylidene-l-0-(4-toluenesulfonyl)glycerol by a nucleophilic substitution of the tosyloxy group <1999AP327>. 

The first example of a mesoionic pyridazine was found during a metabolite study of 4-cyano-3(2//)-pyridazinone. The isolated mesoionic compound 70 was synthesized at low temperature as indicated. When the reaction mixture was heated, the normal N2-riboside (71) was formed. A series of analogous compounds were prepared. Both types of nucleosides are highly sensitive to base, and deblocking of acetyl groups could be achieved with methanolic NaHCOs (84CC422, 84JMC1613). 

The pyridazine nucleosides, related to the naturally occurring nucleosides cytidine and uridine, have been prepared from 4,5-dichloropyridazin-6-one. Its trimethylsilyl derivative (106), when condensed with the protected ) -d-ribofuranose, affords the ) -nucleoside 107. From this the cytidine analog is obtained after treatment with ammonia and deprotection or, via the methoxy... 

From 3-hydrazino-6(l//)-pyridazinone and protected /3-D-ribofuranose the nucleoside 142 (R=Bz) was prepared and after deprotection with sodium methoxide 142 (R=H) was obtained (89MI6).The pyridazine analog of 2 -deoxycitidine was synthesized from 3-methoxy-6-chloropyridazine by intramolecular glycosylation of 143. Compound 143 was treated with Me2S(SMe)BF4 and the oxonium intermediate was hydrolyzed to give the 2 -deoxynucleoside 144 (95MI4). 

Meade EA, Wotring LL, Drach JC et al (1992) Synthesis antiproliferative and antiviral activity of certain 4-aminopyirolo [2, 3-d] pyridazine nucleosides an entry into a novel series of adenosine analogs. J Med Chem 35 526-533... 

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