ANALOGS OF AZEPINOMYCIN AS INHIBITORS OF GUANASE

Synthesis and biochemical screening against guanase of analogues of th e naturally occurring guanase inhibitor azepinomycin (2) are reported. Compound trahydro-4H-imidazo[4,5-e][1,4]diazepine-5,8-dione (3) was s ynthesized in six steps commencing with 1-benzyl-5-nitroimidazole-4-ca rboxylic acid (5). Compound 3 and its synthetic precursor trahydro-4H- imidazo[4,5-e][1,4]diazepine-5,8-dione (12) were screened against rabb it liver guanase. Both were found to be moderate inhibitors of the enz yme with K-i's in the range of 10(-4) M.