title: Synthesis and antibacterial activity of lactivicin derivatives.
abstract: The chemical modification of the 4-acetylamino group on the cycloserine moiety of lactivicin (1a) was carried out. The lactivicin derivatives (1d, k--p and w) having heterocyclic acylamino groups which have been often utilized in beta-lactam antibiotics showed potent antibacterial activities. Ester prodrugs (7a--d) of lactivicin derivatives were also prepared in order to improve the bioavailability on oral administration. The pivaloyloxymethyl (POM) esters (7a and 7b) and 1-ethoxycarbonyloxyethyl (EOE) ester (7c) were found to have slightly improved protective effect in vivo compared with their parent compounds 1c and 1k.
authors.affiliation: Research and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Tamura
authors.forename: Y
authors.initials: Y
authors.lastname: Matsushita
authors.forename: Y
authors.initials: Y
authors.lastname: Kawano
authors.forename: K
authors.initials: K
authors.lastname: Yoshioka
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D008826:Microbial Sensitivity Tests; D010455:Peptides; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D010456:Peptides, Cyclic; C051231:lactivicin