9-n-(1-propyl)erythromyclamine and Streptococcal-Infections

A series of new 9-N-alkyl derivatives of 9(S)-erythromycylamine has been synthesized by reductive alkylation of erythromycylamine with aliphatic aldehydes and sodium cyanoborohydride. Alternative syntheses employing hydrogenation methods have also been developed. These new 9-N-alkyl derivatives possess excellent antimicrobial activity in vitro and in vivo, especially when administered orally to treat experimental infections in mice. From structure-activity studies, 9-N-(1-propyl)erythromycylamine (LY281389) was selected as the most efficacious derivative. These methods have also been extended to the synthesis of some 9-N,N-dialkyl derivatives of erythromycylamine.

Topics: Alkylation; Animals; Bacterial Infections; Chemical Phenomena; Chemistry; Erythromycin; Magnetic Resonance Spectroscopy; Mice; Molecular Structure; Rats; Staphylococcal Infections; Streptococcal Infections; Structure-Activity Relationship