Journal of Medicinal Chemistry 1997-03-14

Repromicin derivatives with potent antibacterial activity against Pasteurella multocida.

J W McFarland, S J Hecker, B H Jaynes, M R Jefson, K M Lundy, C B Vu, E A Glazer, S A Froshauer, S F Hayashi, B J Kamicker, C P Reese, J A Olson

文献索引：J. Med. Chem. 40(6) , 1041-5, (1997)

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摘要

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.