Coumarin inhibitors of gyrase B with N-propargyloxy-carbamate as an effective pyrrole bioisostere

✍ Scribed by Anne-Marie Periers; Patrick Laurin; Didier Ferroud; Jean-Luc Haesslein; Michel Klich; Claudine Dupuis-Hamelin; Pascale Mauvais; Patrice Lassaigne; Alain Bonnefoy; Branislav Musicki

• Publisher: Elsevier Science
• Year: 2000
• Tongue: English
• Weight: 183 KB
• Volume: 10
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/s0960-894x(99)00654-x

✦ Synopsis

AbstractÐThe synthesis and biological pro®le in vitro of a series of coumarin inhibitors of gyrase B bearing a N-propargyloxycarbamate at C-3 H 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 H N-alkoxycarbamates.