title: Discovery of RWJ-54428 (MC-02,479), a new cephalosporin active against resistant gram-positive bacteria.
abstract: The discovery of RWJ-54428 (MC-02,479), a new cephalosporin displaying promising activity against sensitive and resistant Gram-positive bacteria, is described. Progressive structural modification from the previously reported 3-phenylthiocephem MC-02,331 afforded an overall increase in potency against MRSA while retaining other key properties such as acceptable solubility and serum binding. Evaluation of the in vitro potency and in vivo efficacy of a series of closely related compounds resulted in selection of RWJ-54428 (MC-02,479) for further studies.
authors.affiliation: Microcide Pharmaceuticals, Inc., Mountain View, California 94043, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hecker
authors.forename: T W
authors.initials: TW
authors.lastname: Glinka
authors.forename: A
authors.initials: A
authors.lastname: Cho
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Zhang
authors.forename: M E
authors.initials: ME
authors.lastname: Price
authors.forename: S
authors.initials: S
authors.lastname: Chamberland
authors.forename: D
authors.initials: D
authors.lastname: Griffith
authors.forename: V J
authors.initials: VJ
authors.lastname: Lee
mesh_terms: D002511:Cephalosporins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure
chemical_list: D002511:Cephalosporins; C420727:RWJ 54428