Discovery and development of moxalactam (6059‐S): The chemistry and biology of 1‐oxacephems

The cephalosporin antimicrobial agents: a comprehensive review

“…Ceftriaxone and ceftazidime are both very polar compounds and 62.5% and 8696, respectively, of a dose appeared in the urine within 24 h; very little of this renal elimination is believed to occur via tubular secretion as concurrent administration of probenecid did not alter the excretion of these compounds (Hoffstedt et al, 1983;Saito, 1983;Barriere & Flaherty, 1984;Matsui et al, 1984). Probenecid administration also did not affect excretion of moxalactam and further canine studies confirmed that renal elimiriation was mainly via glomerular filtration (Otsuka et al, 1981).…”

“…Unlike cefazolin, the heterocyclic thiomethyl moiety found on cefamandole, moxalactam, cefoperazone, and cefotetan significantly enhances the antibacterial activity of these compounds (Christensen,198 1). This methyltetrazolethiomethyl substituent also somewhat limits the renal tubular secretion of these agents (Otsuka et al, 1981;Barriere & Flaherty, 1984). Further modification of this group via the substitution of an acidic function in place of the methyl on the tetrazole ring resulted in two agents, cefonicid and ceforanide, which exhibited high serum levels and prolonged half-lives in humans due to enhanced serum protein binding and decreased renal excretion (Berges et al, 1976;Gottstein et al, 1976); unfortunately these pharmacologic effects have not been as pronounced in dogs as in humans.…”

Naturally Occurring β-Lactams

“…This was first achieved by a novel acyl exchange reaction (176,177). Under appropriate conditions the cephamycin C ester (204) can be converted to diacyl derivatives such as (205). Removal of the trichloroethyl protecting groups leads to formation of the piperidone (206) and the new cephamycin ester (207).…”

β-Lactam Antibiotics: Structure-Activity Relationships

“…The lack of significant differences between these analogs, which combine the effects of the aminothiazole acetyl side chain and the oxa-substitution for sulfur, may signal that this compound type is approaching the limits of antibiotic activity for the p-lactams. Synthetic approaches and structureactivity relationships that led to its selection for clinical evaluation have been reviewed along with the biological properties of moxa lac tam (OTSUKA et al 1981).…”