Synthesis of an N-aminopyrazinonium analogue of cytidine

J Med Chem. 1983 Feb;26(2):283-6. doi: 10.1021/jm00356a033.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytidine / analogs & derivatives*
  • Cytidine / chemical synthesis
  • Cytidine / therapeutic use
  • Cytidine Deaminase / metabolism
  • Indicators and Reagents
  • Kidney / enzymology
  • Leukemia L1210 / drug therapy
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Inbred Strains
  • Structure-Activity Relationship

Substances

  • Indicators and Reagents
  • Cytidine
  • 1,2-diamino-4-beta-ribofuranosylpyrazin-2-onium
  • Cytidine Deaminase