Design of inhibitors against guanase: Synthesis and biochemical evaluation of analogues of azepinomycin

As part of a program to design rational, mechanism-based inhibitors of guanase, we report here the synthesis and biochemical screening of two analogues of azepinomycin (1 and 2), a naturally occurring inhibitor of guanase, known to mimic the transition-state of the enzyme-catalyzed reaction. Our biochemical results show that compounds 1 and 2 are competitive inhibitors with Ki of 2.01 ± 0.16 × 10−5 and 5.36 ± 0.14 × 10−5 M, respectively.