2-alkylidene-aminoguanidines and methods of use therefor
AssigneesThe Rockefeller University, Alteon Inc.
InventorsPeter C. Ulrich, Anthony Cerami
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Abstract
The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging) which contain 2-alkylidene aminoguanidines and derivatives thereof. Accordingly, a composition is disclosed which comprises an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
Claims32
A method for treating an animal to inhibit the formation of advanced glycosylation endproducts 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 ##STR4## wherein R.sub.1 is hydrogen or acyl;
- R.sub.2 is hydrogen or lower alkyl;
- X is a substituent selected from the group consisting of lower alkyl, carboxy, carboxymethyl, or a phenyl or pyridyl group, optionally substituted by halogen, lower alkyl, hydroxy lower alkyl, hydroxy, or acetylamino with the proviso that when X is a phenyl or pyridyl group, optionally substituted, then R.sub.2 is hydrogen;
- and their biocompatible and pharmaceutically acceptable acid addition salts, and mixtures thereof;
- and a carrier therefor.
A method of inhibiting 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 of a composition comprising a compound selected from the group consisting of compounds of the formula ##STR5## wherein R.sub.1 is hydrogen or acyl;
- R.sub.2 is hydrogen or lower alkyl;
- X is a substituent selected from the group consisting of lower alkyl, carboxy, carboxymethyl, or a phenyl or pyridyl group, optionally substituted by halogen, lower alkyl, hydroxy lower alkyl, hydroxy, or acetylamino with the proviso that when X is a phenyl or pyridyl group, optionally substituted, then R.sub.2 is hydrogen;
- and their biocompatible and pharmaceutically acceptable acid addition salts, and mixtures thereof;
- and a carrier therefor.
Dependencies are inferred from the claim text.