Preventing and reversing the formation of advanced glycosylation endproducts

A pharmaceutical composition for administration to an animal to inhibit the advanced glycosylation of a target protein, and reverse pre-formed advanced glycosylation crosslinks, within said animal, comprising a pharmaceutically effective amount of a compound selected from the group consisting of compounds of the formula ##STR25## wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen, hydroxy(lower)alkyl, lower aceloxy(lower)alkyl, lower alkyl, lower alkenyl, or R.sup.1 and R.sup.2 together with their ring carbons may be an aromatic fused ring, optionally substituted by one or more amino, halo or alkylenedioxy groups;

• Z is hydrogen or an amino group;
• Y is amino, a group of the formula ##STR26## wherein R is a lower alkyl, alkoxy, hydroxy, amino or an aryl group, said aryl group optionally substituted by one or more lower alkyl, lower alkoxy, halo, dialkylamino, hydroxy, nitro or alkylenedioxy groups;
• a group of the formula
• --CH.sub.2 R'
• wherein R' is hydrogen, or a lower alkyl, lower alkynyl, or aryl group;
• or a group of the formula ##STR27## wherein R" is hydrogen and R"' is a lower alkyl group, optionally substituted by an aryl group, or an aryl group, said aryl group optionally substituted by one or more lower alkyl, halo, or alkoxylcarbonyl groups;
• or R" and R"' are both lower alkyl groups;
• X is a halide, tosylate, methanesulfonate or mesitylenesulfonate ion;
• and mixtures thereof, and a pharmaceutically acceptable carrier therefor.

A method for inhibiting the advanced glycosylation of a target protein, and reversing pre-formed advanced glycosylation crosslinks, comprising contacting the target protein with an effective amount of composition comprising a compound selected from the group consisting of compounds of the formula ##STR28## wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen, hydroxy(lower)alkyl, lower aceloxy(lower)alkyl, lower alkyl, lower alkenyl, or R.sup.1 and R.sup.2 together with their ring carbons may be an aromatic fused ring, optionally substituted by one or more amino, halo or alkylenedioxy groups;

• Z is hydrogen or an amino group;
• Y is amino, a group of the formula ##STR29## wherein R is a lower alkyl, alkoxy, hydroxy, amino or an aryl group, said aryl group optionally substituted by one or more lower alkyl, lower alkoxy, halo, dialkylamino, hydroxy, nitro or alkylenedioxy groups;
• a group of the formula
• --CH.sub.2 R'
• wherein R' is hydrogen, or a lower alkyl, lower alkynyl, or aryl group;
• or a group of the formula ##STR30## wherein R" is hydrogen and R"' is a lower alkyl group, optionally substituted by an aryl group, or an aryl group, said aryl group optionally substituted by one or more lower alkyl, halo, or alkoxylcarbonyl groups;
• or R" and R"' are both lower alkyl groups;
• X is a halide, tosylate, methanesulfonate or mesitylenesulfonate ion;
• and mixtures thereof, and a carrier therefor.

A method for treating an animal to inhibit the formation of advanced glycosylation endproducts, and reverse pre-formed advanced glycosylation crosslinks, of a target protein within said animal, said method comprising administering an effective amount of a pharmaceutical composition, said pharmaceutical composition comprising a compound selected from the group consisting of compounds of the formula ##STR31## wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen, hydroxy(lower)alkyl, lower aceloxy(lower)alkyl, lower alkyl, lower alkenyl, or R.sup.1 and R.sup.2 together with their ring carbons may be an aromatic fused ring, optionally substituted by one or more amino, halo or alkylenedioxy groups;

• Z is hydrogen or an amino group;
• Y is amino, a group of the formula ##STR32## wherein R is a lower alkyl, alkoxy, hydroxy, amino or an aryl group, said aryl group optionally substituted by one or more lower alkyl, lower alkoxy, halo, dialkylamino, hydroxy, nitro or alkylenedioxy groups;
• a group of the formula
• --CH.sub.2 R'
• wherein R' is hydrogen, or a lower alkyl, lower alkynyl, or aryl group;
• or a group of the formula ##STR33## wherein R" is hydrogen and R"' is a lower alkyl group, optionally substituted by an aryl group, or an aryl group, said aryl group optionally substituted by one or more lower alkyl, halo, or alkoxylcarbonyl groups;
• or R" and R"' are both lower alkyl groups;
• X is a halide, tosylate, methanesulfonate or mesitylenesulfonate ion;
• and mixtures thereof, and a pharmaceutically acceptable carrier therefor.

A method of inhibiting and reversing the discoloration of teeth resulting from non-enzymatic browning in the oral cavity which comprises administration of an amount effective to inhibit the formation of advanced glycosylation endproducts, and reverse pre-formed advanced glycosylation crosslinks, of a composition comprising a compound selected from the group consisting of compounds of the formula ##STR34## wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen, hydroxy(lower)alkyl, lower aceloxy(lower)alkyl, lower alkyl, lower alkenyl, or R.sup.1 and R.sup.2 together with their ring carbons may be an aromatic fused ring, optionally substituted by one or more amino, halo or alkylenedioxy groups;

• Z is hydrogen or an amino group;
• Y is amino, a group of the formula ##STR35## wherein R is a lower alkyl, alkoxy, hydroxy, amino or an aryl group, said aryl group optionally substituted by one or more lower alkyl, lower alkoxy, halo, dialkylamino, hydroxy, nitro or alkylenedioxy groups;
• a group of the formula
• --CH.sub.2 R'
• wherein R' is hydrogen, or a lower alkyl, lower alkynyl, or aryl group;
• or a group of the formula ##STR36## wherein R" is hydrogen and R"' is a lower alkyl group, optionally substituted by an aryl group, or an aryl group, said aryl group optionally substituted by one or more lower alkyl, halo, or alkoxylcarbonyl groups;
• or R" and R"' are both lower alkyl groups;
• X is a halide, tosylate, methanesulfonate or mesitylenesulfonate ion;
• and mixtures thereof, and a pharmaceutically acceptable carrier therefor.

A compound of the formula ##STR38## wherein R.sup.1, R.sup.2 and Z are hydrogen;

• Y is a group of the formula ##STR39## wherein R is a lower alkyl, alkoxy other than methoxy, hydroxy, amino or an aryl group, said aryl group optionally substituted by one or more lower alkyl, lower alkoxy, halo, dialkylamino, hydroxy, nitro or alkylenedioxy groups, with the proviso that Y is not 2-phenyl-2-oxoethyl or 2-(3'-methoxyphenyl)-2-oxoethyl;
• a group of the formula
• --CH.sub.2 R'
• wherein R' is hydrogen, or a lower alkyl, lower alkynyl, or aryl group;
• or a group of the formula ##STR40## wherein R" is hydrogen and R"' is a lower alkyl group, optionally substituted by an aryl group, or an aryl group, said aryl group optionally substituted by one or more lower alkyl, halo, or alkoxylcarbonyl groups;
• or R" and R"' are both lower alkyl groups;
• X is a halide, tosylate, methanesulfonate or mesitylenesulfonate ion.

A compound of the formula ##STR41## wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen, hydroxy(lower)alkyl, lower acyloxy(lower)alkyl, lower alkyl, lower alkenyl, or R.sup.1 and R.sup.2 together with their ring carbons may be an aromatic fused ring;

• optionally substituted by one or more amino, halo or alkylenedioxy groups;
• Z is hydrogen or an amino group;
• Y is amino, a group of the formula ##STR42## wherein R is a lower alkyl, alkoxy, hydroxy, amino or an aryl group, said aryl group optionally substituted by one or more lower alkyl, lower alkoxy, halo, dialkylamino, hydroxy, nitro or alkylenedioxy groups;
• a group of the formula
• --CH.sub.2 R'
• wherein R' is hydrogen, a lower alkyl or aryl group;
• with the provisos that either Y or Z is an amino group, that when Y is amino and R.sup.2 is hydrogen, then R.sup.1 is other than hydrogen or a lower alkyl group, and when Y is amino, R.sup.1 and R.sup.2 are not methyl;
• and
• X is a halide, tosylate, methanesulfonate or mesitylenesulfonate ion.

A compound of the formula ##STR48## wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen, hydroxy(lower)alkyl, lower acyloxy(lower)alkyl, lower alkyl, lower alkenyl, or R.sup.1 and R.sup.2 together with their ring carbons may be an aromatic fused ring;

• optionally substituted by one or more amino, halo or alkylenedioxy groups;
• Z is hydrogen;
• Y is an alkynylmethyl group or a group of the formula ##STR49## wherein R is an aryl group optionally substituted by one or more lower alkyl, halo, or alkoxylcarbonyl groups, or a lower alkyl group substituted by an aryl group, said aryl group optionally substituted by one or more lower alkyl, halo, or alkoxylcarbonyl groups;
• and
• X is a halide, tosylate, methanesulfonate or mesitylenesulfonate ion.