Synthesis and guanase inhibition studies of a novel ring-expanded purine analogue containing a 5:7-fused, planar, aromatic heterocyclic ring system

Abstract

The synthesis of a novel planar, potentially aromatic, ring-expanded xanthine analogue ( 1), containing the 5:7-fused imidazo[4,5-e][1,4]diazepine ring system, along with guanase inhibition studies are reported. The compound was synthesized in six steps, starting from 1-benzyl-5-nitroimidazole-4-carboxylic acid ( 2), and was biochemically screened against rabbit liver guanase. Compound 1 is a moderate competitive inhibitor of the enzyme with a K i of 2.27 ± 0.66 × 10 −4 M.