Novel effectors of dipeptidyl peptidase IV

Abstract

Dipeptide compounds and compounds analogous to dipeptide compounds that are formed from an amino acid and a thiazolidine or pyrrolidine group, and salts thereof used in the treatment of impaired glucose tolerance, glycosuria, hyperlipidaemia, metabolic acidoses, diabetes mellitus, diabetic neuropathy and nephropathy and also of sequelae of diabetes mellitus in mammals.

Description

CROSS REFERENCE TO OTHER APPLICATIONS [0001] The present application is a continuation of application U.S. Ser. No. 10 / 361,956, filed on Feb. 10, 2003, which is a continuation of application U.S. Ser. No. 09 / 723,638, filed on Nov. 28, 2000, which claims priority of DE 198 / 23831.2 filed on May 28, 1998 and subsequent PCT EP 99 / 03712 application filed on May 28, 1999.BACKGROUND OF THE INVENTION [0002] According to the current state of the art, hyperglycaemia and associated causes and sequelae (including diabetes mellitus) are treated by the administration of insulin (e.g. material isolated from bovine pancreas or obtained by genetic engineering techniques) to the diseased organisms in various forms of administration. All methods known hitherto, including more modern procedures, are distinguished by the requirement of a large amount of material, by high costs and often by a distinct impairment of the quality of life of the patients. The conventional method (daily i.v. insulin injection...

AI Technical Summary

Benefits of technology

[0012] The aim of the invention is therefore to provide new (especially activity-reducing) effectors for the treatment of e.g. impaired glucose tolerance, glycosuria, hyperlipidaemia, metabolic acidoses, diabetes mellitus, diabetic neuropathy and nephropathy and also of sequelae of diabetes mellitus in mammals, and a simple method of treating such diseases.

Problems solved by technology

All methods known hitherto, including more modern procedures, are distinguished by the requirement of a large amount of material, by high costs and often by a distinct impairment of the quality of life of the patients.

The conventional method (daily i.v. insulin injection, customary since the 1930s) treats the acute symptoms of the disease, but after prolonged use leads inter alia to serious vascular changes (arteriosclerosis) and nerve damage.

Such transplants require a high level of technical resources.

Furthermore, they involve a surgical intervention into the recipient organism, which is associated with risks, and even in the case of cell transplants require methods of suppressing or circumventing the immune system.

It has been established that those compounds, especially L-threo-isoleucyl thiazolidide, are good effectors for DP IV and DP IV-analogous enzyme activities, but the use of that compound may give rise to certain problems in the case of some patients or some forms of the disease:

It is also possible that too high a level of inhibitor activity and the permanent administration of the same medicament, especially in view of the life-long duration of treatment, may result in undesirable side-effects.

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