Coumarin inhibitors of gyrase B with N-propargyloxy-carbamate as an effective pyrrole bioisostere.
作者信息
Periers A M, Laurin P, Ferroud D, Haesslein J L, Klich M, Dupuis-Hamelin C, Mauvais P, Lassaigne P, Bonnefoy A, Musicki B
机构信息
Medicinal Chemistry, Hoechst Marion Roussel, Romainville, France.
出版信息
Bioorg Med Chem Lett. 2000 Jan 17;10(2):161-5. doi: 10.1016/s0960-894x(99)00654-x.
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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