CEPHALOSPORIN DERIVATIVES HAVING IMPROVED ANTI-MICROBIAL ACTIVITY, PARTICULARLY, FOR METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS(MRSA) STRAIN, ITS PHARMACEUTICALLY ACCEPTABLE SALTS AND MANUFACTURING PROCESS THEREOF

摘要

PURPOSE: Cephalosporin derivatives, its pharmaceutically acceptable salts and a manufacturing process thereof are provided, which cephalosporin derivatives have improved anti-microbial activity, particularly, for methicillin-resistant Staphylococcus aureus(MRSA) strain, so that they can be useful for antibiotics. CONSTITUTION: The cephalosporin derivatives represented by formula (I), or pharmaceutically acceptable salts thereof are provided, wherein X, Y and Z are the same or different, and independently hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 halogenoalkyl, C1-6 alkoxy alkyl or C3-6 cycloalkyl; R1 is an isoxazol compound in which the 3-site is substituted with a compound of formula (A), wherein Q is a substituent useful for cephalosporin-based compound, and is selected from hydrogen, halogen, hydroxyl, mercapto, cyano, carboxy, carboxylic acid, ester, carbamoyloxy, carbamoyl, N,N-dimethylcarbamoyl, C1-4 alkyl, C1-4 alkyloxy, halogen substituted alkyl, aryl or hetero ring substituent; and R2 is hydrogen, an ester-forming group as an ester of carboxy group, salt-forming atom or carboxy-protecting group. The process for preparing the cephalosporin derivatives represented by formula (I), or pharmaceutically acceptable salts thereof comprises reacting an ilide compound of formula (VI) with an aldehyde compound of formula (VII) in the presence of base and organic solvent at -40 to 25 deg. C.