Synthesis of New 5′-Norcarbocyclic Aza/Deaza Purine Fleximers-Noncompetitive Inhibitors of E.coli Purine Nucleoside Phosphorylase

A new series of flexible 5 '-norcarbocyclic aza/deaza-purine nucleoside analogs were synthesized from 6-oxybicyclo[3.1.0.]hex-2-ene and pyrazole-containing fleximer analogs of heterocyclic bases using the Trost procedure. The compounds were evaluated as potential inhibitors of E. coli purine nucleoside phosphorylase. Analog 1-3 were found to be noncompetitive inhibitors with inhibition constants of 14-24 mM. From the data obtained, it can be assumed that the new 5 '-norcarbocyclic nucleoside analogs interact with the active site of the PNP like natural heterocyclic bases. But at the same time the presence of a cyclopentyl moiety with 2 ' and 3 ' hydroxyls is necessary for the inhibitory properties, since compounds 8-10, without those groups did not exhibit an inhibitory effect under the experimental conditions.

Automated summary

A series of new 5'-norcarbocyclic nucleoside and aza/deaza-purine nucleoside analogs were synthesized and evaluated as potential inhibitors of E. coli purine nucleoside phosphorylase. The compounds showed inhibitory effects, but only when a cyclopentyl moiety was present at specific positions.