Repromicin derivatives with potent antibacterial activity against Pasteurella multocida
J W McFarland1, S J Hecker, B H Jaynes
1Central Research Division, Pfizer Inc., Groton, Connecticut 06340, USA. mcfarland@pfizer.com
Abstract:
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.
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