Effect of latamoxef (moxalactam) and its related compounds on platelet aggregation in vitro structure activity relationships

Latamoxef, 1-S replaced and/or decarboxylated derivatives of latamoxef, compounds possessing a partial structure of latamoxef, and a beta-lactam ring-opened derivative of latamoxef were examined for their effects on human platelet aggregation in vitro. Latamoxef produced a dose-dependent inhibition of ADP-induced platelet aggregation at high concentrations over about 2000 micrograms/ml (or 4 mM), and the potency was similar to that produced by cefotaxime, carbenicillin or ceftizoxime. Replacement of the oxygen atom in the oxacephem ring with a sulfur atom caused no significant change in the potency. The decarboxylated derivatives of latamoxef and the 1-S replaced analogue of latamoxef showed stronger inhibition for both ADP- and collagen-induced aggregation than the parent compounds. The effects of the compounds possessing a partial structure of latamoxef were weaker than that of latamoxef, but the effect of the beta-lactam ring-opened compound was about 3-fold stronger than that of latamoxef. These data suggest that neither the oxygen atom in the oxacephem ring nor the carboxyl group in the amide side chain is responsible for the inhibitory effect of latamoxef on platelet aggregation.