Synthesis and evaluation of ureido and vinylureidopenicillins as inhibitors of intraruminal lactic acid production

Abstract

A series of 14 vinylureidopenicillins and a series of 9 ureidopenicillins were prepared by reaction of 6-aminopenicillanic acid with vinyl isocyanates and isocyanates. These compounds were evaluated for their potential to protect ruminants against lactic acidosis. The compounds were tested for inhibition of in vitro ruminal lactic and propionic acid production, and six compounds inhibited lactic acid production to less than 10% of control at doses of 0.31 microgram/mL or lower, whereas they did not inhibit propionic acid production at doses greater than 10 micrograms/mL. The most active compounds also were screened for general antibacterial activity and were found to be weakly active against Gram-positive bacteria. The structure--activity relationships are discussed for both series. Triethylammonium 6-[3[2-(4-tert-butylphenyl)vinyl]ureido]penicillanate (4) was chosen for evaluation as an inhibitor of intraruminal lactic acidosis in vivo.

Enhancement of the activity of the antibiotic laidlomycin by acylation and the 13C NMR spectra of laidlomycin and its esters.

“…In conclusion, we have demonstrated that acylation of laidlomycin at C-26 leads to compounds with a superior profile of antibiotic activity relative to the parent compound in two in vitro rumen fer- Laidlomycin (1) Monensin (2) Laidlomycin propionate (5) Laidlomycin butyrate (6) Laidlomycin hexanoate (11) Laidlomycin octanoate (15) Laidlomycin decanoate (16) Infected controls…”