Synthesis of 2-alkynyl substituted 4′-thioadenosine derivatives and their binding affinities at the adenosine receptors

Abstract

On the basis of high binding affinity of 2-hexynyl-N 6- methyladenosine and N 6-substituted-4′-thioadenosine derivatives at the A3 adenosine receptor (AR), novel 2-alkynyl-substituted-N 6-methyl-4′-thioadenosine derivatives, combining the characteristics of two classes of nucleosides were designed and synthesized from D-gulonic γ-lactone via palladium-catalyzed cross coupling reaction as a key step. Among compounds tested, only compound 3b showed moderate binding affinity at the human A3 adenosine receptor without binding affinities at other subtypes. © 2008 The Pharmaceutical Society of Korea.