| Abstract
| - A novel series of erythromycin derivatives has been discovered with potent activity againstkey respiratory pathogens, including those resistant to erythromycin. These compounds arecharacterized by having an aryl group tethered to the C-6 position of the erythronolide skeleton.Extensive structural modification of the C-6 moiety led to the discovery of several promisingcompounds with potent activity against both mef- and erm-mediated resistant Streptoccoccuspneumoniae. Preliminary mechanistic studies indicated that the new macrolides are potentprotein synthesis inhibitors, which interact with methylated ribosomes isolated from resistantorganisms. In experimental animal models, these compounds exhibited excellent in vivo efficacyand balanced pharmacokinetic profiles.
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