Synthesis and structure-activity relationships of new 9-N-alkyl derivatives of 9(S)-erythromycylamine |
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| Authors: | H A Kirst J A Wind J P Leeds K E Willard M Debono R Bonjouklian J M Greene K A Sullivan J W Paschal J B Deeter |
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| Affiliation: | Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285. |
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| Abstract: | 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. |
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