N63-carboxamides of N15-alkyl and N15,N15-dialkyl derivatives of teicoplanin and deglucoteicoplanin.
The synthesis and biological properties of a series of N63-carboxamides of 15-N-alkylated derivatives of teicoplanin A2 (CTA) and its aglycone (TD) are described. Among the compounds, those carrying hydrophilic groups or ionizable amino functions on the N15-alkyl chain are more soluble in water than parent N15-methylated or unmodified amides. Selected compounds were more active in vitro than CTA or TD, and a few of them were also slightly more efficacious in vivo than the parent antibiotics in streptococcal septicemia in the mouse. Their degree of activity varied with the structure and length of the N15-alkyl chains.
Marion Merrell Dow Research Institute, Lepetit Research Center, Gerenzano (Varese), Italy.
A
A
Malabarba
R
R
Ciabatti
J
J
Kettenring
R
R
Scotti
G
G
Candiani
M
M
Berti
R
R
Pallanza
B P
BP
Goldstein
D000478:Alkylation; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016470:Bacteremia / Q000188:drug therapy; D051379:Mice; D008826:Microbial Sensitivity Tests; D013290:Streptococcal Infections / Q000188:drug therapy; D013329:Structure-Activity Relationship; D017334:Teicoplanin / Q000031:analogs & derivatives*
D000577:Amides; D000900:Anti-Bacterial Agents; D017334:Teicoplanin