Novel imidazo[1,2-c]pyrimidine base-modified nucleosides: synthesis and antiviral evaluation.
The preparation of a series of novel 6-(beta-D-ribofuranosyl)-2-alkyl/aryl-6H-imidazo[1,2-c]pyrimidin-5-one nucleosides and the 2-nitrile nucleosides, 6-(beta-D-ribofuranosyl)-5-oxo-5,6-dihydro-imidazo[1,2-c]pyrimidine-2-carbonitrile and 2R and 2S isomers of 6-(beta-D-ribofuranosyl)-5-oxo-2,3,5,6-tetrahydro-imidazo[1,2-c]pyrimidine-2-carbonitrile, is described using two synthetic approaches. The nucleoside mimetics described were evaluated against a wide range of viral types and strains in cell culture. With the exception of one nucleoside, which displayed anti-CMV activity at toxic concentrations, none of the compounds showed antiviral activity most likely due to a lack of substrate recognition by viral and/or cellular nucleoside kinases.
Kifli
Nurolaini
N
Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, Wales, UK.
De Clercq
Erik
E
Balzarini
Jan
J
Simons
Claire
C
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011724:Pyridazines / Q000737:chemistry*; D014709:Vero Cells / Q000187:drug effects
D000998:Antiviral Agents; D007093:Imidazoles; D009705:Nucleosides; D011724:Pyridazines