US 5,399,560 A · 1,2,4-triazine products resulting from the inhibition of advanced glycosylation

Abstract

The mechanism of the inhibition of advanced glycosylation by aminoguanidine and other hydrazine type compounds was investigated using a solution of one or two molecules of aminoguanidine or other hydrazine type compound incubated with an Amadori product (1-propylamine-1-deoxy-D-fructose) under physiological conditions. This inhibition was found to proceed through the reactive intermediate 1-propylamino-1, 4-dideoxyosone to form the corresponding triazine and the dehydrazone of 1,4-dideoxyglucosone, respectively. The triazine and dehydrazone products are useful as macrophage stimulants to activate a macrophage to effect removal of advanced glycosylation endproducts (AGEs). Additionally, they can be used in a variety of investigative methods in an effort to measure the extent of nonenzymatic glycosylation of a protein sample wherein aminoguanidine or other hydrazine-type compound is or was present during the glycosylation process.

Claims7

Dependent claims

A compound selected from the group consisting of compounds of the formula ##STR10## wherein R is a lower alkyl group of 1 to 6 carbon atoms;

R.sub.1 is hydrogen or a lower alkyl group of 1-6 carbon atoms, amino, or hydroxy, or together with R.sub.2 represent a lower alkylene bridge of 2-4 carbon atoms;
R.sub.2 is hydrogen, or a lower alkyl group of 1-6 carbon atoms, a hydroxyethyl group or R.sub.2 may be taken together with R.sub.1 as noted above;
R.sub.3 is hydrogen, a lower alkyl group of 1-6 carbon atoms or may be together with R.sub.1 a lower alkylene bridge of 2-4 carbon atoms;
and R.sub.4 is hydrogen, a lower alkyl group of 1-6 carbon atoms or together with R.sub.3 is a lower alkylene bridge of 2-4 carbon atoms;
and their pharmaceutically acceptable salts.

2 more elements

Dependencies are inferred from the claim text.

Facts

Application

07/956,722Filed 1 Oct 1992 · continuation in part

Priority

19 Mar 1984

Granted

21 Mar 1995

Term ends

Not estimatedThe source records don’t support an estimate.

Classification35 codes

G01N 33/6842
General methods of protein analysis not limited to specific proteins or families of proteins: proteomic analysis of subsets of protein mixtures…
A61K 8/4966
With more than one nitrogen as the only hetero atom: triazines or their condensed derivatives
A61K 31/15
Amines: oximes ; Hydrazines ; Hydrazones ; Imines
A61K 31/155
Amines: amidines , e.g. guanidine , isourea , isothiourea

Family

Serial590,820Parent of this division · filed 19 Mar 1984

Serial590,820Parent of this continuation-in-part · filed 19 Mar 1984

Serial798,032Parent of this division · filed 14 Nov 1985

Serial798,032Parent of this continuation-in-part · filed 14 Nov 1985

Serial119,958Parent of this continuation-in-part · filed 13 Nov 1987

Serial220,504Parent of this continuation-in-part · filed 18 Jul 1988

Serial264,930Parent of this continuation-in-part · filed 2 Nov 1988

Serial481,869Parent of this division · filed 20 Feb 1990

Serial605,654Parent of this continuation-in-part · filed 30 Oct 1990

Serial805,200Parent of this continuation-in-part · filed 10 Dec 1991

US 5,238,963 AParent of this continuation-in-part

US 5,140,048 AParent of this continuation-in-part

US 5,128,360 AParent of this division

US 4,758,583 AParent of this division

US 4,665,192 AParent of this division

US 4,983,604 AParent of this continuation-in-part

US 4,908,446 AParent of this continuation-in-part

US 4,758,583 AParent of this continuation-in-part

US 4,665,192 AParent of this continuation-in-part

US 5,399,560 AThis patent

From the US filing history. Foreign family members aren’t listed.

1,2,4-triazine products resulting from the inhibition of advanced glycosylation

Life of this patent

1,2,4-triazine products resulting from the inhibition of advanced glycosylation

Life of this patent

Abstract

Claims7