Synthesis and Biological Activity of 2,6-Disubstituted 7-Deazapurine Ribonucleosides

Abstract

Several series of 2,6-disubstituted 7-deazapurine ribonucleosides were synthesized to investigate their biological activities. The key-intermediate chloronucleosides were prepared by an anion-base glycosylation with 2-amino-6-chloro-7-deazapurine. The target compounds were obtained by diazotation, either Suzuki and Sonogashira reactions in the case of 2-arylethynyl-6-hetaryl nucleosides or two consecutive Suzuki reactions in the case of 2,6-diaryl nucleosides. The sequence of diazotation and the first Suzuki reaction is flexible and can be changed depending on the target compounds. Some of the final nucleosides showed moderate cytotoxic activity against several cancer cell lines and low antagonistic activity against a panel of adenosine receptors.