Anti-inflammatory glucocorticoid compounds for topical ophthalmic use

A topically administrable, ophthalmic pharmaceutical composition for treating ophthalmic inflammation, which comprises an anti-inflammatory effective amount of a C-21 thioether corticosteroid derivative of the formula:

• ##STR7## wherein:
• X=H or halogen;
• Y=OH, (.dbd.O), C.sub.1 -C.sub.5 O-alkyl or C.sub.1 -C.sub.5 OC(.dbd.O)alkyl;
• Z=saturated or unsaturated bond;
• R.sub.2 =H, OH, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.5 oxalkyl, or C.sub.1 -C.sub.5 oxoalkyl;
• R.sub.3 =H, OH or C.sub.1 -C.sub.3 alkyl;
• R.sub.2 & R.sub.3 taken together can form ##STR8## wherein A and B are independently H, C.sub.1 -C.sub.3 alkyl, or phenyl, provided however that if either A or B is phenyl, the other is H;
• R.sub.4 =halogen, H, OH, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.5 oxalkyl, or C.sub.1 -C.sub.5 oxoalkyl;
• and
• R.sub.1 =optionally unsaturated and/or substituted C.sub.1 -C.sub.7 alkyl, branched alkyl, cycloalkyl, carboxyalkyl, hydroxyalkyl, or aralkyl;
• or optionally substituted aryl;
• wherein the substituents are halogen, amino, nitro, optionally unsaturated C.sub.1 -C.sub.6 alkyl, aminoalkyl, alkoxy or carboxy;
• 5-membered heterocyclic ring, optionally benzo-fused, containing at least one C atom and any combination of one or more O and/or N and/or S atoms, optionally unsaturated and/or substituted as above, and wherein the benzo-ring can be substituted as above;
• or
• 6-membered heterocyclic ring containing at least two C atoms and any combination of one or more O and/or N atoms, optionally unsaturated and/or substituted as above;
• and
• pharmaceutically acceptable salts and esters thereof.

A method of treating ophthalmic inflammatory disorders which comprises topically administering to the affected eye an anti-inflammatory effective amount of a C-21 thioether corticosteroid derivative of the formula:

• ##STR10## wherein:
• X=H or halogen;
• Y=OH, (.dbd.O), C.sub.1 -C.sub.5 O-alkyl or C.sub.1 -C.sub.5 OC(.dbd.O)alkyl;
• Z=saturated or unsaturated bond;
• R.sub.2 =H, OH, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.5 oxalkyl, or C.sub.1 -C.sub.5 oxoalkyl;
• R.sub.3 =H, OH or C.sub.1 -C.sub.3 alkyl;
• R.sub.2 & R.sub.3 taken together can form ##STR11## wherein A and B are independently H, C.sub.1 -C.sub.3 alkyl, or phenyl, provided however that if either A or B is phenyl, the other is H;
• R.sub.4 =halogen, H, OH, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.5 oxalkyl, or C.sub.1 -C.sub.5 oxoalkyl;
• and
• R.sub.1 optionally unsaturated and/or substituted C.sub.1 -C.sub.7 alkyl, branched alkyl, cycloalkyl, carboxyalkyl, hydroxyalkyl, or aralkyl;
• or optionally substituted aryl;
• wherein the substituents are halogen, amino, nitro, optionally unsaturated C.sub.1 -C.sub.6 alkyl, aminoalkyl, alkoxy or carboxy;
• 5-membered heterocyclic ring, optionally benzo-fused, containing at least one C atom and any combination of one or more O and/or N and/or S atoms, optionally unsaturated and/or substituted as above, and wherein the benzo-ring can be substituted as above;
• or
• 6-membered heterocyclic ring containing at least two C atoms and any combination of one or more O and/or N atoms, optionally unsaturated and/or substituted as above;
• and
• pharmaceutically acceptable salts and esters thereof.