Synthesis and biological activity of 5-amino- and 5-hydroxyquinolones, and the overwhelming influence of the remote N1-substituent in determining the structure-activity relationship.

摘要: A series of 5-amino- and 5-hydroxyquinolone antibacterials substituted at C7 with a select group common piperazinyl 3-aminopyrrolidinyl side chains was prepared. These 5-substituted derivatives were compared to the analogous 5-hydrogen compounds for antiinfective activity by using DNA gyrase inhibition, minimum inhibitory concentrations against variety bacteria, in vivo efficacy mouse infection model. The influence on structure-activity relationships varied substituents C8 (H, F, Cl) N1 (ethyl, cyclopropyl, difluorophenyl) also studied. results showed that several conclusions regarding side-chain bulk C7, effect halogen C8, C5-amino greatly influenced choice N1-substituent. Several outstanding broad spectrum quinolones identified this work. In particular, potency 7-piperazinyl could be enhanced judicious C5-, C8-, N1-substituents.