The synthesis and biological profile in vitro of a series of coumarin inhib
itors of gyrase B bearing a N-propargyloxy-carbamate at C-3' of noviose is
presented. Replacement of the 5-methylpyrrole-2-carboxylate of coumarin dru
gs with an N-propargyloxycarbamate bioisostere leads to analogues with impr
oved antibacterial activity. Analysis of crystal structures of coumarin ant
ibiotics with the 24 kDa N-terminal domain of the gyrase B protein provides
a rational for the excellent inhibitory potency of C-3' N-alkoxycarbamates
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