Cyclic phenolic thioethers

A pharmaceutical composition for use in the treatment of lipoxygenase mediated conditions which comprises a therapeutically effective amount of a compound of the formula:

• ##STR79## wherein R.sup.1 and R.sup.2 are the same or different and independently represent tert-alkyl or phenyl;
• R.sup.3 represents hydrogen or alkyl;
• X represents --(CH.sub.2).sub.w --B--(CH.sub.2).sub.y -- wherein B represents CH.sub.2 and w and y can each independently be an integer from 0 to 3 with the proviso that the sum of w+y is equal to or less than 3;
• A represents O or S(O).sub.n wherein n is 0, 1, or 2;
• p is an integer from 0 to 4;
• and R represents NR.sup.5 R.sup.6 wherein R.sup.5 is hydrogen or alkyl, and R.sup.6 is hydrogen, alkyl, heterocycloalkyl, subtituted heterocycloalkyl, cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, phenylalkyl, or substituted phenylalkyl, or NR.sup.5 R.sup.6 together form a heterocyclic ring which may optionally be substituted;
• or a pharmaceutically acceptable salt thereof.

A method of treating lipoxygenase mediated conditions which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of the formula:

• ##STR80## wherein R.sup.1 and R.sup.2 are the same or different and independently represent tert-alkyl or phenyl;
• R.sup.3 represents hydrogen or alkyl;
• X represents --(CH.sub.2).sub.w --B--(CH.sub.2).sub.y -- wherein B represents CH.sub.2 and w and y can each independently be an integer from 0 to 3 with the proviso that the sum of w+y is equal to or less than 3;
• A represents O or S(O).sub.n wherein n is 0, 1, or 2;
• p is an integer from 0 to 4;
• and R represents:
• (a) alkyl;
• or
• (b) NR.sup.5 R.sup.6 wherein R.sup.5 is hydrogen or alkyl, and R.sup.6 is hydrogen, alkyl, heterocycloalkyl, substituted heterocycloalkyl, cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, phenylalkyl, or substituted phenylalkyl, or NR.sup.5 R.sup.6 together form a heterocyclic ring which may optionally be substituted;
• or a pharmaceutically acceptable salt thereof.

A method of treating inflammatory disease which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of the formula:

• ##STR81## wherein R.sup.1 and R.sup.2 are the same or different and independently represent tert-alkyl or phenyl;
• R.sup.3 represents hydrogen or alkyl;
• X represents --(CH.sub.2).sub.w --B--(CH.sub.2).sub.y -- wherein B represents CH.sub.2 and w and y can each independently be an integer from 0 to 3 with the proviso that the sum of w+y is equal to or less than 3;
• A represents O or S(O).sub.n wherein n is 0, 1, or 2;
• p is an integer from 0 to 4;
• and R represents:
• (a) alkyl;
• or
• (b) NR.sup.5 R.sup.6 wherein R.sup.5 is hydrogen or alkyl, and R.sup.6 is hydrogen, alkyl, heterocycloalkyl, substituted heterocycloalkyl, cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, phenylalkyl, or substituted phenylalkyl, or NR.sup.5 R.sup.6 together form a heterocyclic ring which may optionally be substituted;
• or a pharmaceutically acceptable salt thereof.

A method of treating allergic reactions which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of the formula:

• ##STR82## wherein R.sup.1 and R.sup.2 are the same or different and independently represent tert-alkyl or phenyl;
• R.sup.3 represents hydrogen or alkyl;
• X represents --(CH.sub.2).sub.w --B--(CH.sub.2).sub.y -- wherein B represents CH.sub.2 and w and y can each independently be an integer from 0 to 3 with the proviso that the sum of w+y is equal to or less than 3;
• A represents O or S(O).sub.n wherein n is 0, 1, or 2;
• p is an integer from 0 to 4;
• and R represents:
• (a) alkyl;
• or
• (b) NR.sup.5 R.sup.6 wherein R.sup.5 is hydrogen or alkyl, and R.sup.6 is hydrogen, alkyl, heterocycloalkyl, substituted heterocycloalkyl, cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, phenylalkyl, or substituted phenylalkyl, or NR.sup.5 R.sup.6 together form a heterocyclic ring which may optionally be substituted;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula:

• ##STR83## wherein R.sup.1 and R.sup.2 are the same or different and independently represent tert-alkyl or phenyl;
• R.sup.3 represents hydrogen or alkyl;
• X represents --(CH.sub.2).sub.w --B--(CH.sub.2).sub.y -- wherein B represents O, S, or CH.sub.2 and w and y can each independently be an integer from 0 to 3 with the proviso that the sum of w+y is equal to or less than 3;
• and Z represents hydroxy, halogen, sulfate ester or perfluoroacyl ester, with the proviso that the DL mixture of compounds is excluded where B represents CH.sub.2 and Z represents hydroxy.

A method of inhibiting the generation of superoxide which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of the formula:

• ##STR84## wherein R.sup.1 and R.sup.2 are the same or different and independently represent tert-alkyl or phenyl;
• R.sup.3 represents hydrogen or alkyl;
• X represents --(CH.sub.2).sub.w --B--(CH.sub.2).sub.y -- wherein B represents O, S, or CH.sub.2 and w and y can each independently be an integer from 0 to 3 with the proviso that the sum of w+y is equal to or less than 3;
• A represents O or S(O).sub.n wherein n is 0, 1, or 2;
• p is an integer from 0 to 4;
• and R represents:
• (a) alkyl;
• or
• (b) NR.sup.5 R.sup.6 wherein R.sup.5 is hydrogen or alkyl, and R.sup.6 is hydrogen, alkyl heterocycloalkyl, substituted heterocycloalkyl, cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, phenylalkyl, or substituted phenylalkyl, or NR.sup.5 R.sup.6 together form a heterocyclic ring which may optionally be substituted;
• or a pharmaceutically acceptable salt thereof.

A method of stimulating the generation of superoxide which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of the formula:

• ##STR85## wherein R.sup.1 and R.sup.2 are the same or different and independently represent tert-alkyl or phenyl;
• R.sup.3 represents hydrogen or alkyl;
• X represents --(CH.sub.2).sub.w --B--(CH.sub.2).sub.y -- wherein B represents O, S, or CH.sub.2 and w and y can each independently be an integer from 0 to 3 with the proviso that the sum of w+y is equal to or less than 3;
• A represents O or S(O).sub.n wherein n is 0, 1, or 2;
• p is an integer from 0 to 4;
• and R is NR.sup.5 R.sup.6 wherein R.sup.5 is hydrogen or alkyl and R.sup.6 is heterocycloalkyl;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula:

• ##STR86## wherein R.sup.1 and R.sup.2 are tert-alkyl;
• A is sulfur;
• p is 1 or 2;
• R.sup.3 is hydrogen or alkyl of 1 to 4 carbon atoms;
• X is (CH.sub.2).sub.m wherein m is 1 or 2;
• and R is NR.sup.5 R.sup.6 wherein R.sup.5 is hydrogen or alkyl of 1 to 6 carbon atoms and R.sup.6 is hydrogen, alkyl of 1 to 6 carbon atoms or heterocycloalkyl wherein the alkyl moiety has 1 to 4 carbon atoms, or a pharmaceutically acceptable salt thereof.