Coumarin inhibitors of gyrase B with N-propargyloxy-carbamate as an effective pyrrole bioisostere |
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Authors: | Periers A M Laurin P Ferroud D Haesslein J L Klich M Dupuis-Hamelin C Mauvais P Lassaigne P Bonnefoy A Musicki B |
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Institution: | Medicinal Chemistry, Hoechst Marion Roussel, Romainville, France. |
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Abstract: | The synthesis and biological profile in vitro of a series of coumarin inhibitors of gyrase B bearing a N-propargyloxycarbamate at C-3' of noviose is presented. Replacement of the 5-methylpyrrole-2-carboxylate of coumarin drugs with an N-propargyloxycarbamate bioisostere leads to analogues with improved antibacterial activity. Analysis of crystal structures of coumarin antibiotics 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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