Bicyclic pyrazolidinones, compositions and use

A compound of the formula:

• ##STR14## wherein either R.sub.1 and R.sub.2 is hydrogen, C.sub.1 to C.sub.6 alkyl, substituted C.sub.1 to C.sub.6 alkyl substituted with one or two halogen, hydroxy, protected hydroxy, amino, protected amino, C.sub.1 to C.sub.7 acyloxy, nitro, carboxy, protected carboxy, carbaoyl, carbamoyloxy, cyano, methylsulfonylanimo or C.sub.1 to C.sub.4 alkyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 phenylalkyl wherein the C.sub.1 to C.sub.6 alkyl portion is substituted C.sub.1 -C.sub.6 alkyl as defined above and wherein;
• the phenyl group may also be substituted phenyl substituted by 1 or 2 groups chosen from the group consisting of halogen, hydroxy, protected hydroxy, nitro, C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.4 alkoxy, carboxy, protected carboxy, carboxymethyl, protected carboxymethyl, hydroxymethyl, protected hydroxymethyl, aminomethyl, protected aminomethyl, trifluoromethyl, and a methylsulfornylamino group;
• phenyl, substituted phenyl as defined above;
• nitro or cyano;
• a group of the formula
• --CX.sub.3
• wherein X is fluoro, chloro, bromo or iodo;
• a group of the formula ##STR15## wherein Z is 0, 1, 2 and R.sub.5 is C.sub.1 to C.sub.6 alkyl, substituted C.sub.1 to C.sub.6 alkyl as defined above;
• phenyl, substituted phenyl as defined above;
• C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 phenylalkyl substituted on the C.sub.1 to C.sub.6 alkyl portion as defined above, and wherein the phenyl portion is substituted phenyl as defined above;
• a group of the formula
• --COR.sub.6
• wherein R.sub.6 is hydrogen, C.sub.1 to C.sub.6 alkyl, substituted C.sub.1 to C.sub.6 alkyl as defined above;
• perfluoro C.sub.2 to C.sub.4 alkyl, trihalomethyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 phenylalkyl substituted on the C.sub.1 to C.sub.6 alkyl portion or the phenyl portion as defined above;
• phenyl or substituted phenyl as defined above;
• a group of the formula
• --COOR.sub.7
• wherein R.sub.7 is hydrogen, an organic or inorganic cation chosen from the group consisting of lithium, sodium, potassium, barium and calcium cations, ammonium, dibenzylammonium, benzylammonium, 2-hydroxyethylammonium, bis(2-hydroxyethyl)ammonium, phenylethylbenzylammonium, dibenzylethylenediammonium, the protonated forms of procaine, quinine, N-methylglucosamine, glycine, ornithine, histidine, phenylglycine, lysine and arginine;
• C.sub.1 to C.sub.6 alkyl, substituted on the C.sub.1 to C.sub.6 alkyl as defined above;
• C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 phenylalkyl substituted on the C.sub.1 to C.sub.6 alkyl portion or phenyl portion as defined above phenyl, substituted phenyl as defined above;
• a carboxy protecting group, or a non-toxic, metabolically-labile ester-forming group chosen from the group consisting of methoxymethyl, ethoxymethyl, iso-propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, iso-propoxyethyl, 5-methyl-2-oxo-1,3-dioxolen-4-ylmethyl, 5-phenyl-2-oxo-1,3-dioxolen-4-ylmethyl, methylthiomethyl, ethylthiomethyl, iso-propylthiomethyl, pivloyloxymethyl, .alpha.-acetoxymethyl, ethoxycarbonyl-1-methyl, .alpha.-acetoxyethyl, 3-phthalidyl, 5,6-dimethylphthalidyl, 1-(ethoxycarbonyloxy)-eth-1-yl, and 1-(methylaminocarbonyloxy)eth-1-yl;
• and the other of R.sub.1 or R.sub.2 is a group of the formula
• --COOR.sub.9
• wherein R.sub.9 is hydrogen, an organic or inorganic cation chosen from the group consisting of lithium, sodium, potassium, barium and calcium cations, ammonium, dibenzylammonium, benzylammonium, 2-hydroxyethylammonium, bis(2-hydroxyethyl)ammonium, phenylethylbenzyl ammonium, dibenzylethylenediammonium, the protonated forms of procaine, quinine, N-methylglucosamine, glycine, ornithine, histidine, phenylglycine, lysine and arginine a carboxy protecting group, or a non-toxic, metabolically-labile ester-forming group as defined above for R.sub.7 ;
• and R.sub.3 and R.sub.4 are the same or different and are hydrogen, C.sub.1 to C.sub.6 alkyl, substituted C.sub.1 to C.sub.6 alkyl as defined above for R.sub.1 or R.sub.2 C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 phenylalkyl substituted on the C.sub.1 to C.sub.6 alkyl portion or the phenyl portion as defined above for R.sub.1 or R.sub.1 ;
• phenyl, substituted phenyl as defined above for R.sub.1 or R.sub.2 ;
• or a group of the formula
• --COOR.sub.10
• wherein R.sub.10 has the same definition as R.sub.7 ;
• with the exception that, when R.sub.1 and R.sub.2 are a group of the formula
• --COOCH.sub.3,
• R.sub.3 and R.sub.4 are not methyl;
• or a pharmaceutically-acceptable salt thereof.