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 K(i) of 2.01+/-0.16 x 10(-5) and 5.36+/-0.14 x 10(-5) M, respectively.