Analogues of azepinomycin as inhibitors of guanase.

Synthesis and biochemical screening against guanase of analogues of the naturally occurring guanase inhibitor azepinomycin (2) are reported. Compound 6-amino-5,6,7,8,-tetrahydro-4H-imidazo[4,5-e][1,4]diazepine-5,8-dione (3) was synthesized in six steps commencing with 1-benzyl-5-nitroimidazole-4-carboxylic acid (5). Compound 3 and its synthetic precursor 3-benzyl-6-(N-benzyloxycarbonyl)amino-5,6,7,8-tetrahydro-4H-imidazo[4,5- e] [1,4]diazepine-5,8-dione (12) were screened against rabbit liver guanase. Both were found to be moderate inhibitors of the enzyme with K's in the range of 10(-4) M.