REPROMICIN DERIVATIVES WITH POTENT ANTIBACTERIAL ACTIVITY AGAINST PASTEURELLA-MULTOCIDA

Reductive amination of repromicin with polyfunctional amines has led t o 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 t he recognition that among certain known macrolides increasing lipophil icity results in diminished in vivo activity. One repromicin derivativ e, 20-{N-[3-(dimethylamino)propyl] -N-L-alanylamino}-20-deoxorepromici n (35), was selected for advanced evaluation. At 5 mg/kg, a single sub cutaneous dose was found to control induced pasteurellosis in swine an d induced respiratory disease in cattle.