Synthesis of an N-aminopyrazinonium analogue of cytidine.
An N-aminated pyrazine analogue of cytidine, in which the pyrimidine N(3) ring nitrogen and C(4) amino group were replaced by a C-amino and an N-amino function, respectively, was prepared as a potential deaminase-resistant cytidine antimetabolite. The nucleoside 1,2-diamino-4-beta-D-ribofuranosylpyrazin-2-onium chloride (6) was a mild cytostatic agent but was neither a substrate for nor an inhibitor of mouse kidney cytidine deaminase. It ionized with a lower pKa than expected. The anion did not undergo the dimerization usually observed with N-imino heterocyclic ylides but unerwent hydrolysis of the 2-amino group to yield a 1-aminopyrazine-2,3-dione nucleoside.
D000818:Animals; D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D003564:Cytidine Deaminase / Q000378:metabolism; D007202:Indicators and Reagents; D007668:Kidney / Q000201:enzymology; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D003562:Cytidine; C037435:1,2-diamino-4-beta-ribofuranosylpyrazin-2-onium; D003564:Cytidine Deaminase