In vitro and in vivo evaluation of C-20- and C-23-modified derivatives of tylosin against veterinary pathogens.

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Abstract
Three series of semi-synthetic derivatives of tylosin-related macrolides were evaluated for utility in veterinary medicine. 23-Modified derivatives of 5-O-mycaminosyltylonolide (OMT) possessed potent acitivity in vitro against species of Pasteurella and Mycoplasma. An experimental infection in chicks caused by Pasteurella multocida was utilized to evaluate efficacy; several of these derivatives of OMT effectively treated the infection when given subcutaneously, but none were effective after oral administration in drinking water. Macrolides retaining the 4''-O-mycarosyl moiety (tylosin, DMT) had relatively poor activity against Pasteurella in vitro. Certain 20-modified derivatives of desmycosin demonstrated good oral bioavailibility in chicks and a lead compound with oral efficacy in the Pasteurella infection model was discovered.

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