Esters and amides of non-steroidal anti-inflammatory carboxylic acids which may be used as anti-oxidants, 5-lipoxygenase inhibitors and non-steroidal anti-inflammatory prodrugs

A pharmaceutical composition for preventing or alleviating damage to mammalian tissues comprising an amount of a compound of the following formula effective to decrease inflammation and free radical or oxidative damage in said tissues:

• A--X--(CH.sub.2).sub.n --Y--(CH.sub.2).sub.m --Z
• wherein:
• A is a non-steroidal anti-inflammatory agent originally having a carboxylic acid moiety;
• X is O or NR;
• A--X is an ester or amide linkage derived from the carboxylic acid moiety of the non-steroidal anti-inflammatory agent and the X;
• R is H, C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.6 cycloalkyl;
• Y, if present, is O, NR, C(R).sub.2, CH(OH) or S(O).sub.n' ;
• n is 2 to 4 and m is 1 to 4 when Y is O, NR, or S(O).sub.n' ;
• n is 0 to 4 and m is 0 to 4 when Y is C(R).sub.2 or is not present;
• n is 1 to 4 and m is 0 to 4 when Y is CH(OH);
• n' is 0 to 2;
• and
• Z is selected from the group consisting of:
• ##STR23## wherein:
• R' is H, C(O)R, C(O)N(R).sub.2, PO.sub.3.sup.- or SO.sub.3.sup.- ;
• R" is H or C.sub.1 -C.sub.6 alkyl;
• or a pharmaceutically acceptable salt thereof;
• and a pharmaceutically acceptable vehicle therefore.

A method of preventing or alleviating damage to mammalian tissues which comprises administering a therapeutically effective amount of a composition comprising an amount of a compound of the following formula effective to decrease inflammation and free radical or oxidative damage in said tissues:

• A--X--(CH.sub.2).sub.n --Y--(CH.sub.2).sub.m --Z
• wherein:
• A is a non-steroidal anti-inflammatory agent originally having a carboxylic acid moiety;
• X is O or NR;
• A--X is an ester or amide linkage derived from the carboxylic acid moiety of the non-steroidal anti-inflammatory agent and the X;
• R is H, C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.6 cycloalkyl;
• Y, if present, is O, NR, C(R).sub.2, CH(OH) or S(O).sub.n' ;
• n is 2 to 4 and m is 1 to 4 when Y is O, NR, or S(O).sub.n' ;
• n is 0 to 4 and m is 0 to 4 when Y is C(R).sub.2 or is not present;
• n is 1 to 4 and m is 0 to 4 when Y is CH(OH);
• n' is 0 to 2;
• and
• Z is selected from the group consisting of:
• ##STR25## wherein:
• R' is H, C(O)R, C(O)N(R).sub.2, PO.sup.-.sub.3 or SO.sup.-.sub.3 ;
• R" is H or C.sub.1 -C.sub.6 alkyl;
• or a pharmaceutically acceptable salt thereof;
• and a pharmaceutically acceptable vehicle thereof.