title: Synthesis and structure-activity relationships of new 9-N-alkyl derivatives of 9(S)-erythromycylamine.
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.
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285.
authors.forename: H A
authors.initials: HA
authors.lastname: Kirst
authors.forename: J A
authors.initials: JA
authors.lastname: Wind
authors.forename: J P
authors.initials: JP
authors.lastname: Leeds
authors.forename: K E
authors.initials: KE
authors.lastname: Willard
authors.forename: M
authors.initials: M
authors.lastname: Debono
authors.forename: R
authors.initials: R
authors.lastname: Bonjouklian
authors.forename: J M
authors.initials: JM
authors.lastname: Greene
authors.forename: K A
authors.initials: KA
authors.lastname: Sullivan
authors.forename: J W
authors.initials: JW
authors.lastname: Paschal
authors.forename: J B
authors.initials: JB
authors.lastname: Deeter
mesh_terms: D000478:Alkylation; D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D013203:Staphylococcal Infections / Q000188:drug therapy; D013290:Streptococcal Infections / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: C066283:9-N-(1-propyl)erythromyclamine; C007626:erythromyclamine; D004917:Erythromycin