Patent EP-0202046-A1 (EP)
Inventor: JUNGHEIM LOUIS NICKOLAUS
IPC: A61P31/04
Filed: 1986-04-28
Abstract: 7-Substituted bicyclic pyrazolidinone compounds as antimicrobials and the corresponding intermediates, are discussed or provided. The use of the antimicrobial compounds in pharmaceutical compositions and in methods for treating bacterial infections is set forth. The pyrazolidinone compounds are of the formula
     wherein one of R 1  and R 2  is hydrogen, halo, C 1  to C 6  alkyl, C 1  to C 6  substituted alkyl, perfluoro C 2  to C 4  alkyl, C 7  to C 12  arylalkyl, C 7  to C 12  substituted arylalkyl, phenyl, substituted phenyl, a heterocyclic ring, nitro or cyano;
     a group of the formula
     wherein X is fluoro, chloro, bromo or iodo; a group of the formula
     wherein z is 0, 1 or 2 and R 7  is C 1  to C 6  alkyl, C 1  to C 6  substituted alkyl, phenyl, substituted phenyl, C 7  to C 12  arylalkyl, C 7  to C 12  substituted arylalkyl or a heterocyclic ring; a group of the formula
     wherein R 8  is hydrogen, C 1  to C 6  alkyl, C, to C 6  substituted alkyl, perfluoro C 2  to C 4  alkyl, trihalomethyl, C 7  to C 12  arylalkyl, C 7  to C 12  substituted arylalkyl, phenyl, substituted phenyl, amino, (monosubstituted)amino, or (disubstituted)amino;   
     a group of the formula
     wherein R 9  is hydrogen, an organic or inorganic cation, C 1  to C 6  alkyl, C 1  to C 6  substituted alkyl, C 7  to C 12  arylalkyl, C 7  to C 12  substituted arylalkyl, phenyl, substituted phenyl, a carboxy-protecting group, or a non-toxic, metabolically-labile, ester-forming group; 
     a group of the formula
       
    
     wherein R 10  is hydrogen, an organic or inorganic cation, C 1  to C 5  alkyl, C, to G 6  aubatituted allcyl, C 7  to C 12  arylalkyl, C 7  to C 12  aubatltuted arylalkyl, phenyl, or substituted phenyl; a group of the formula 
           ⊕ wherein -N≡Q is a quaternary ammonium group; or a group of the formula -CH 2 -S-Heterocycllc ring;
     a group of the formula
     wherein R 11  is hydrogen, C 1  to C e  alkyl, C, to C e  substituted alkyl, C 7  to C 12  arylalkyl, C 7  to C 12  substituted arylalkyl, phenyl, substituted phenyl or C 1  to C 7  acyl; or a group of the formula
     wherein R 12  and R 13  are the same or different and are hydrogen, C 1  to C 6  alkyl, C 1  to C 6  substituted alkyl, C 7  to C 12  arylalkyl, C 7  to C 12  substituted arylalkyl, phenyl, substituted phenyl, C 1  to C 7  acyl, or a group of the formula;
     wherein Rq is C, to C 6  alkyl, C 7  to C 12  arylalkyl or phenyl; and the other of R, and R 2  is a group of the formula
     wherein R 14  is hydrogen, an organic or inorganic cation, a carboxy-protecting group or a non-toxic, metabolically-labile ester-forming group; and R 3  and R 4  are the same or different and are hydrogen, C 1  to C 6  alkyl, C 1  to C 6  substituted alkyl, C 7  to C 12  arylalkyl, C 7  to C 12  substituted arylalkyl, phenyl, substituted phenyl or a group of the formula
     wherein R 15  has the same definition as R 9 ;   
     R 5  and R 6  are:
     1) each hydrogen, an amino protecting group; or acyl group derived from a C, to C 30  carboxylic acid;  
provided that at least one of R s  and R 6  must be hydrogen; or   2) taken together to form a phthalimido group; or a pharmaceutically-acceptable salt thereof.