Collect. Czech. Chem. Commun. 2011, 76, 1395-1412
Published online 2011-11-30 13:14:58

Autofluorescent fused-pyrimidine nucleosides: Synthesis and evaluation as permeants and inhibitors of human nucleoside transporters

Ireneusz Nowaka, Vijaya L. Damarajub, Carol E. Cassb, James D. Youngc and Morris J. Robinsa,*

a Department of Chemistry and Biochemistry, Brigham Young University, Provo 84602-5700, Utah, U.S.A.
b Department of Oncology, University of Alberta, Edmonton, Alberta, Canada T6G 1Z2
c Department of Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7


Nucleosides with an aromatic five-membered ring heterocycle (N, O, or S) fused at C4–C5 of pyrimidin-2-one were prepared by ring closures with 5-(alkyn-1-yl)pyrimidin-2-one intermediates, heterocyclic atom replacements, and ring closure with a 5-aminocytidine derivative. Ultraviolet absorption and emission properties of the autofluorescent products enabled studies on permeation and inhibition of the trans-cellular trafficking effected by human equilibrative nucleoside transporters (hENTs). Some of the autofluorescent nucleosides were shown to be potent and selective inhibitors of human concentrative nucleoside transporters (hCNTs) in a companion study reported elsewhere.

Keywords: Alkynylpyrimidine cyclizations; Autofluoresent nucleoside analogues; Nucleoside transport studies; Ring-fused pyrimidines; Sonogashira coupling.

References: 42 live references.