Synthesis and adenosine deaminase inhibitory activity of 3 '-deoxy-1-deazaadenosines

New 1-deazapurine nucleosides were synthesized by coupling 2,6-dichloro-1-d eaza-9H-purine (=5,7-dichloro-3H-imidazo[4,5-b]pyridine) with a 3-deoxyribo se derivative by the acid-catalyzed fusion method. The condensation reactio n gave an anomeric mixture of the N-9-beta-D- and N-9-alpha-D-3'-deoxynucle osides, which were treated with methanolic ammonia at room temperature to o btain the deprotected derivatives. Reaction of the beta-D-anomer with diffe rent amines gave 2-chloro-N-6-substituted nucleosides, which were dechlorin ated to give the corresponding 3'-deoxy-1-deazaadenosines. Biological studi es 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 K, of 2.6 mu M.