Synthesis and Adenosine Deaminase Inhibitory Activity of 3′-Deoxy-1-deazaadenosines

Abstract

New 1-deazapurine nucleosides were synthesized by coupling 2,6-dichloro-1-deaza-9H-purine (=5,7-dichloro-3H-imidazo[4,5-b]pyridine) with a 3-deoxyribose derivative by the acid-catalyzed fusion method. The condensation reaction gave an anomeric mixture of the N9-β-D- and N9-α-D-3′-deoxynucleosides, which were treated with methanolic ammonia at room temperature to obtain the deprotected derivatives. Reaction of the β-D-anomer with different amines gave 2-chloro-N6-substituted nucleosides, which were dechlorinated to give the corresponding 3′-deoxy-1-deazaadenosines. Biological studies on adenosine deaminase from calf intestine showed that the new compounds are inhibitors of the enzyme, the 3′-deoxy-1-deazaadenosine being the most potent one with a Ki of 2.6 μM.