Pyridine ’-nucleosides

A number of imidazo[4,5-c]pyridine nucleosides (3-deazapurine nucleosides) are of special interest because of their biological properties. 3-Deazaadenosine (655) inhibits biochemical methylations by acting as either an inhibitor or substrate of (S)-adenosylhomocysteine hydrolase <79BP1897>. Compound (655) has antiviral <78BBR(82)417> and antimalarial activities <80MI 708-01). 3-Deaz-... 

Azine approach. Diazotization of 3-amino-2-mercaptopyridine is a very convenient way for preparing simple members of this ring system (743) <74CS(6)222>. 7-Amino derivatives (663) are available by the isomerism reaction of u-triazoles (662 R = H) on heating in 1-propanol (72JOC3601). The same transformation occurs in pyridine nucleosides (662 R = (3-D-ribose) (76JOC1449). 

CNT2 SLC28A2 Pyridine nucleosides Adenosine, cladribine, didanoside A... 

CNT3 SLC28A3 Purine and pyridine nucleosides 5-fluorouridine, floxuridine, zebularine, gemcitabine, zalcitabine A... 

N NMR spectroscopy studies of a natural toxic pyridine nucleoside, clitidine, in aqueous solution and X-ray crystallographic analysis in the solid state revealed that the imine 75 is predominant in the both states (98H(47)661). 

Several other enzymes known to be directly involved in the biogenesis of pyridine mononucleotides via salvage and recycling of pyridines and pyridine nucleosides are less ubiquitous than the three families of phosphoribosyltransferases described above. Flere, we briefly describe some of the best-studied salvage enzymes that are captured in Figure 2 and Table 1. 

Trifluorothymidine is a fluorinated pyridine nucleoside structurally related to idoxuridine (55). It has been approved by the U.S. FDA and is a potent, specific inhibitor of replication of HSV-1 in vitro. Its mechanism of action is similar to that of idoxuridine. Like other antiherpes drugs, it is first phos-phorylated by thymidine kinase to mono-, di-, and triphosphate forms, which are then incorporated into viral DNA in place of thymidine to stop the formation of late virus mRNA and subsequent synthesis of the virion proteins. 

Alder adduct spontaneously eliminates nitrogen to afford the pyridine nucleoside <97ZN851>. 

Ci.HuNjOfc, Mr 270.24, cryst., mp. 189-191 °C (monohydrate), [ajp -50.6° (HjO). A highly toxic pyridine nucleoside from the Japanese toadstool Dokusa-sako Clitocybe acromelalga, Basidiomycetes). The LDso (mouse) is less than 50 pg/kg. C. acts as an NAD analogue. The corresponding nucleotide is also present in the fungus. 

The chemistry of pyridine nucleoside analogs ds similar to that of the more widely studied pyrimidine nucleosides. The nucleosides are prepared from... 

Blocked pyridine nucleosides have been phosphorylated with (3-cyanoethyl phosphate anddicyclohexylcarbodiimide, diphenyl phosphorochlori-date, and with triethyl phosphate followed by oxidation. ... 

Pyridine nucleosides. 774 alkylation of. 769 phosphorylation of, 774 preparation from 2-ethoxypyri-dine, 769... 

Standard procedures have been employed in the preparation of various 5-substituted 2 -deoxyuridines, > - including the 5-ethynyl and 5-methyl derivatives, 5-cyclopropyluridine, the 5-(fluoroalkyloxymethyl)uridines (408), and the pyridine nucleosides (409) and (410). The pyridine nucleosides... 

P. Van Roey and C.K. Chu, The crystal and molecular structure of the complex of 2 ,3 -didehydro-2 ,3 -dideoxyguanosine with pyridine. Nucleosides Nucleotides, 11 1229(1992). 

Another predominant zwitterionic tautomer of a pyridine nucleoside, clutidine 33, could be unequivocally assigned by N NMR both in aqueous solution and in the solid state [68]. 

---