Claims
- 1. A method for inhibiting the advanced glycosylation of a target protein comprising contacting the target protein with an effective amount of composition comprising a compound selected from the group consisting of compounds of the formula ##STR3## wherein X is oxygen or nitrogen; R.sub.1 is hydrogen, lower alkyl or aryl;
- R.sub.2 is hydrogen, lower alkyl, lower alkenyl, aryl, or hydroxy lower alkyl;
- R.sub.3 is hydrogen, hydroxy, lower alkyl, aryl, halo, lower alkanoyl, or aryl lower alkyl; and their biologically or pharmaceutically acceptable salts with organic or inorganic bases; and mixtures thereof, and a carrier therefor.
- 2. The method of claim 1 wherein said compound has the formula wherein X is oxygen.
- 3. The method of claim 2 wherein said compound is tetronic acid or a biologically acceptable salt thereof.
- 4. The method of claim 1 wherein said compound has the formula wherein X is nitrogen.
- 5. The method of claim 4 wherein said compound is tetramic acid or a biologically acceptable salt thereof.
- 6. 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 X is oxygen or nitrogen; R.sub.1 is hydrogen, lower alkyl or aryl;
- R.sub.2 is hydrogen, lower alkyl, lower alkenyl, aryl, or hydroxy lower alkyl;
- R.sub.3 is hydrogen, hydroxy, lower alkyl, aryl, halo, lower alkanoyl, or aryl lower alkyl; and their biologically or pharmaceutically acceptable salts with organic or inorganic bases; and mixtures thereof, and a carrier therefor.
- 7. The method of claim 6 wherein said compound has the formula wherein X is oxygen.
- 8. The method of claim 7 wherein said compound is tetronic acid or a pharmaceutically acceptable salt thereof.
- 9. The method of claim 6 wherein said compound has the formula wherein X is nitrogen.
- 10. The method of claim 9 wherein said compound is tetramic acid or a pharmaceutically acceptable salt thereof.
- 11. 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 X is oxygen or nitrogen; R.sub.l is hydrogen, lower alkyl or aryl; R.sub.2 is hydrogen, lower alkyl, lower alkenyl, aryl, or hydroxy lower alkyl; R.sub.3 is hydrogen, lower alkyl, halo, lower alkanoyl, or aryl lower alkyl; and their biologically or pharmaceutically acceptable salts with organic or inorganic bases; and mixtures thereof, and a carrier therefor.
- 12. The method of claim 11 wherein said compound has the formula wherein X is oxygen.
- 13. The method of claim 12 wherein said compound is tetronic acid or a pharmaceutically acceptable salt thereof.
- 14. The method of claim 11 wherein said compound is tetramic acid or a pharmaceutically acceptable salt thereof.
- 15. The method of claim 14 wherein said compound is tetramic acid or a pharmaceutically acceptable salt thereof.
Parent Case Info
This Application is a Continuation-In-Part of Application U.S. Ser. No. 08/027,086, filed Mar. 5, 1993, now abandoned; which is a Divisional of U.S. Ser. No. 07/672,946, filed Mar. 25, 1991, now U.S. Pat. No. 5,218,001; which, in turn, is a Continuation-In-Part of U.S. Ser. No. 07/503,804, filed Apr. 3, 1990, and now U.S. Pat. No. 5,175,192; which is a Continuation-In-Part of U.S. Ser. No. 481,869, filed Feb. 20, 1990 and now U.S. Pat. No. 5,128,360; which is a Continuation-In-Part of U.S. Ser. No. 220,504, filed Jul. 18, 1989, now abandoned; which is a Divisional of U.S. Ser. No. 798,032, filed Nov. 14, 1985, and now U.S. Pat. No. 4,758,583; which is a Continuation-In-Part of U.S. Ser. No. 590,820, filed Mar. 19, 1984 and now U.S. Pat. No. 4,665,192.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4758583 |
Cerami et al. |
Jul 1988 |
|
5218001 |
Ulrich et al. |
Jun 1993 |
|
Non-Patent Literature Citations (14)
Entry |
Brownlee et al., "Aminoguanidine Prevents Diabetes-Induced Arterial Wall Protein Cross-Linking", Science, 232:1629-1632 (1986). |
Brownlee et al., "Inhibition of Glucose-derived Protein Crosslinking and Prevention of Early Diabetic Changes in Glomerular Basement Membrane by Aminoguanidine", Diabetes, 35 Suppl. 1:42A (1986). |
Bucala et al., "Advanced Glycosylation: Chemistry, Biology, and Implications for Diabetes and Aging", Advances in Pharmacology, 23:1-34, Academic Press (1992). |
Eble et al., "Nonenzymatic Glucosylatioin and Glucose-dependent Cross-linking of Protein", J. Biol. Chem., 258:9406-9412 (1983). |
Hayase et al., "Aging of Proteins: Immunological Detection of a Glucose-derived Pyrrole Formed during Maillard Reaction in Vivo", J. Biol. Chem., 263:3758-3764 (1989). |
Nicholls et al., Nicholls et al., "Advanced Glycosylation End-Products in Experimental Murine Diabetic Nephropathy", Lab. Invest., 60 No. 4:486 (1989) Lab. Invest., 60 No. 4:486 (1989). |
Nordbo, "Ability of Chlorhexidine and Benzalkonium Chloride to Catalyze Browning Reaction", J. Dent. Res., 58:1429 (1979). |
Oimomi et al., "The Effects of Aminoguandine on 3-Deoxyglucosone in the Maillard Reaction", Agric. Biol. Chem., 53(6):1727-1728 (1989). |
Oimomi et al., "Aminoguanidine inhibits 3-deoxyglucosone during the advanced maillard reaction", Diabetes Research and Clinical Practice, 6:311-313 (1989). |
Sell and Monnier, "Structure Elucidation of a Senescence Cross-link from Human Extracellular Matrix", J. Biol. Chem., 264:21597-21602 (1989). |
CA 98:119144p, Rehse et al., 1982. |
CA 108:55786, Meul et al., 1987. |
CA 108:186563, Meul, 1988. |
Merck Index, #855, 11th Ed., 1989. |
Divisions (2)
|
Number |
Date |
Country |
Parent |
672946 |
Mar 1991 |
|
Parent |
798032 |
Nov 1985 |
|
Continuation in Parts (5)
|
Number |
Date |
Country |
Parent |
27086 |
Mar 1993 |
|
Parent |
503804 |
Apr 1990 |
|
Parent |
481869 |
Feb 1990 |
|
Parent |
220504 |
Jul 1989 |
|
Parent |
590820 |
Mar 1984 |
|