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Reductive amination of the C-20 aldehyde group of tylosin and related macrolides yielded a large series of derivatives with potentially useful antibiotic properties. Evaluation of these new compounds was conducted on the basis of: 1) Broad antimicrobial spectrum in vitro, with particular emphasis on inhibition of Pasteurella multocida and Pasteurella haemolytica; 2) in vivo efficacy, especially when given orally, against P. multocida in experimental infections in chicks; and 3) bioavailability after oral administration to laboratory animals. The most useful activity was found within a series of derivatives produced by reductive amination of desmycosin with secondary amines., info:eu-repo/semantics/published

A large series of C-23-modified derivatives of 5-O-mycaminosyltylonolide were synthesized, in which the C-23 hydroxyl group was replaced by halo, aryl ether or thioether, azido, amino or dialkylamino substituents via SN2 displacement reactions. The majority of derivatives possessed excellent in vitro activity against a variety of aerobic and anaerobic bacteria. While some of the compounds treated experimental infections in rodents by parenteral administration, none showed any significant efficacy or bioavailability after oral dosing. Novel rearrangement products were obtained from some of the reactions; these were identified as 13,23-cyclopropyl-12,22-exomethylene and 13,23-cyclopropyl-12-alkoxy derivatives., info:eu-repo/semantics/published

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 activity 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 bioavailability in chicks and a lead compound with oral efficacy in the Pasteurella infection model was discovered., info:eu-repo/semantics/published

Modification of the aldehyde group in tylosin and related macrolide antibiotics dramatically enhanced the oral efficacy of the derivatives against experimental infections caused by susceptible bacteria in laboratory animals. A large number and wide variety of aldehyde-modified macrolide derivatives were prepared, utilizing the Mitsunobu reaction and other chemical transformations. Evaluation of in vitro and in vivo antimicrobial activity indicated that derivatives of demycarosyltylosin (desmycosin) combined the broadest spectrum of antimicrobial activity with the best efficacy and bioavailability after oral administration., info:eu-repo/semantics/published

A large number and wide variety of acyl derivatives of the tylosin-related macrolides 23-demycinosyltylosin (DMT), 23-demycinosyloxytylosin (DMOT) and 5-O-mycaminosyltylonolide (OMT) were synthesized and evaluated. This encompassed conversion of the hydroxyl groups at 2',4' and 23 of the appropriate macrolides to the corresponding esters, in which a variety of different substitution patterns were examined. A wide range of acyl substituents was investigated, particularly for 23-O-acyl derivatives of OMT, since these were substantially more active in vitro than OMT itself. However, the acyl derivatives which were prepared demonstrated no substantial improvement in oral efficacy or bioavailability over the parent macrolides., info:eu-repo/semantics/published