title: Novel cephalosporin derivatives possessing a bicyclic heterocycle at the 3-position. Part I: Synthesis and biological activities of 3-(benzothiazol-2-yl)thiocephalosporin derivatives, CP0467 and related compounds.
abstract: A series of cephalosporin derivatives with various bicyclic heterocycles at the C-3 position was synthesized and evaluated for antibacterial activity. Among them CP0467 (3a) showed excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) (MIC90 = 6.25 microg/mL), and extremely high affinity for the penicillin binding protein 2' of MRSA (I50 = 0.49 microg/mL). Furthermore, 3a showed a long-acting pharmacokinetic profile in mice (AUC(infinity) = 482.3 microg/h/mL and T(1/2) = 1.9 h).
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsushima
authors.forename: K
authors.initials: K
authors.lastname: Iwamatsu
authors.forename: A
authors.initials: A
authors.lastname: Tamura
authors.forename: S
authors.initials: S
authors.lastname: Shibahara
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis*; D000818:Animals; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D015169:Colony Count, Microbial; D004353:Drug Evaluation, Preclinical; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006602:Hexosyltransferases; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism; D010458:Peptidyl Transferases; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis*
chemical_list: D000081:Acetamides; D001426:Bacterial Proteins; C115098:CP 0467; D002352:Carrier Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D013844:Thiazoles; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase