Structure-activity studies of 20-deoxo-20-amino derivatives of tylosin-related macrolides.
Reductive amination of the C-20 aldehyde group of tylosin and related macrolides yielded a large series of derivatives with potentially useful antibiotic properties. Evaluation of these new compounds was conducted on the basis of: 1) Broad antimicrobial spectrum in vitro, with particular emphasis on inhibition of Pasteurella multocida and Pasteurella haemolytica; 2) in vivo efficacy, especially when given orally, against P. multocida in experimental infections in chicks; and 3) bioavailability after oral administration to laboratory animals. The most useful activity was found within a series of derivatives produced by reductive amination of desmycosin with secondary amines.
Kirst
H A
HA
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Willard
K E
KE
Debono
M
M
Toth
J E
JE
Truedell
B A
BA
Leeds
J P
JP
Ott
J L
JL
Felty-Duckworth
A M
AM
Counter
F T
FT
Ose
E E
EE
D000586:Amination; D000818:Animals; D002645:Chickens; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010325:Pasteurella / Q000187:drug effects*; D010326:Pasteurella Infections / Q000188:drug therapy; D013290:Streptococcal Infections / Q000188:drug therapy; D013297:Streptococcus pyogenes / Q000187:drug effects; D013329:Structure-Activity Relationship; D015645:Tylosin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D015645:Tylosin