title: [Possibility of drug design of beta-lactam antibiotics effective for multiresistant gram-positive pathogens].
abstract: Since infectious diseases are caused by various bacteria and most of them are treated empirically, broad-spectrum antibiotics are required. To expand the spectrum, an imidazopyridazinium group and aminothiadiazole group were introduced to 3- and 7-side chain of cephem nucleus, respectively. The resulting compound, cefozopran, was able to permeate not only outer membrane of Pseudomonas aeruginosa but also envelope of gram-positive bacteria, which functioned as a barrier to antipseudomonal cephalosporins, and showed potent activity against wide variety of bacteria including those which produced a large amount of cephalosporinase and were resistant to third-generation cephalosporins. In spite of the broad antibacterial spectrum, cefozopran only weakly affected gastrointestinal flora of mice and prevented colonization by MRSA.
authors.affiliation: Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Ltd.
authors.forename: K
authors.initials: K
authors.lastname: Okonogi
authors.forename: A
authors.initials: A
authors.lastname: Miyake
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D002511:Cephalosporins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004064:Digestive System / Q000382:microbiology; D015195:Drug Design; D018432:Drug Resistance, Multiple; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D051379:Mice; D018440:beta-Lactam Resistance; D000097586:Cefozopran
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097586:Cefozopran