RESUMO
SAR studies and optimization of various modified Hygromycin A fluoroalkyl ethers, which led to the discovery of the highly potent 4'-(2-cyclopropyl-2-fluoroethyl ether) antibacterial CE-156811 (1) derived from truncation of the ribose ring and difluorination of the phenyl found in Hygromycin A, are discussed.
Assuntos
Antibacterianos/química , Cinamatos/química , Dioxóis/química , Higromicina B/análogos & derivados , Administração Oral , Animais , Antibacterianos/síntese química , Antibacterianos/farmacocinética , Cães , Avaliação Pré-Clínica de Medicamentos , Haplorrinos , Higromicina B/química , Camundongos , Testes de Sensibilidade Microbiana , Ratos , Relação Estrutura-AtividadeRESUMO
Novel hygromycin A derivatives bearing a variety of functionalized aminocyclitol moieties have been synthesized in an effort to increase the antibacterial activity and drug-like properties of this class of agents. A systematic study of the effect of alkylation and removal of the hydroxyls of the aminocyclitol directed us to a series of alkylated aminocyclitol derivatives with improved gram-positive activity.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Cinamatos/síntese química , Cinamatos/farmacologia , Higromicina B/análogos & derivados , Higromicina B/síntese química , Higromicina B/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
We evaluated a novel truncated hygromycin A analog in which the furanose ring was replaced with a 2-fluoro-2-cyclopropylethyl substituent for its activity against multidrug resistant gram-positive bacteria and compared its activity to the activities of linezolid, quinupristin-dalfopristin, and vancomycin. CE-156811 demonstrated robust in vitro activity against gram-positive bacteria that was comparable to that of linezolid.
