Repromicin derivatives with potent antibacterial activity against Pasteurella multocida.
Reductive amination of repromicin with polyfunctional amines has led to new macrolide antibacterial agents, some of which are highly potent against the Gram-negative pathogen Pasteurella multocida both in vitro and in a mouse infection model. A key element in this discovery was the recognition that among certain known macrolides increasing lipophilicity results in diminished in vivo activity. One repromicin derivative, 20-[N-[3-(dimethylamino)-propyl]-N-L-alanylamino]-20-deoxorepro micin (35), was selected for advanced evaluation. At 5 mg/kg, a single subcutaneous dose was found to control induced pasteurellosis in swine and induced respiratory disease in cattle.
McFarland
J W
JW
Central Research Division, Pfizer Inc., Groton, Connecticut 06340, USA. mcfarland@pfizer.com
Hecker
S J
SJ
Jaynes
B H
BH
Jefson
M R
MR
Lundy
K M
KM
Vu
C B
CB
Glazer
E A
EA
Froshauer
S A
SA
Hayashi
S F
SF
Kamicker
B J
BJ
Reese
C P
CP
Olson
J A
JA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D007933:Leucomycins / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018942:Macrolides; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010326:Pasteurella Infections / Q000188:drug therapy / Q000662:veterinary; D016979:Pasteurella multocida / Q000187:drug effects*; D015645:Tylosin / Q000031:analogs & derivatives / Q000494:pharmacology
C105327:20-(N-(3-(dimethylamino)propyl)-N-alanylamino)-20-deoxorepromicin; D000900:Anti-Bacterial Agents; D007933:Leucomycins; D018942:Macrolides; C052318:tylosin B; C060286:rosaramicin; D015645:Tylosin