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.

1 . Dipeptide compound formed from an amino acid and a thiazolidine or pyrrolidine group, and salts thereof. 
     
     
         2 . Dipeptide compound according to  claim 1 , characterised in that the amino acid is selected from a natural amino acid. 
     
     
         3 . Dipeptide compound according to  claim 1 , characterised in that at a concentration of 10 μm it brings about a reduction in the activity of dipeptidyl peptidase IV or DP IV-analogous enzyme activities of at least 10%. 
     
     
         4 . Dipeptide compound according to  claim 3 , characterised in that it brings about a reduction in activity of at least 40%. 
     
     
         5 . Dipeptide compound according to  claim 1 , characterised in that the amino acid is selected from leucine, valine, glutamine, proline, isoleucine, asparagine and aspartic acid. 
     
     
         6 . Dipeptide compound according to  claim 1 , namely L-threo-isoleucyl pyrrolidide, L-allo-isoleucyl thiazolidide, 1-allo-isoleucyl pyrrolidide and salts thereof. 
     
     
         7 . Dipeptide compound according to  claim 1 , characterised in that the salts are organic salts such as acetates, succinates, tartrates or fumarates, or inorganic acid radicals such as phosphates or sulphates. 
     
     
         8 . Salts of dipeptide compounds according to  claim 1 , characterised in that they are present in a molar ratio of dipeptide compound to salt of 1:1 or 2:1. 
     
     
         9 . Fumaric salts of dipeptide compounds according to  claim 1 . 
     
     
         10 . The fumaric salt according to  claim 9 , consisting of fumaric salts of L-threo-isoleucyl thiazolidide or fumaric salts of L-allo-isoleucyl thiazolidide. 
     
     
         11 . A pharmaceutical composition comprising least one compound or a salt thereof according to  claim 1  optionally in combination with one or more pharmaceutically acceptable carriers and/or solvents. 
     
     
         12 . Pharmaceutical composition according to  claim 11 , wherein the carrier is a carrier for parenteral or enteral formulations. 
     
     
         13 . Pharmaceutical composition according to  claim 11 , suitable for oral administration. 
     
     
         14 . Pharmaceutical composition according to  claim 11 , additionally comprising an active ingredient having hypoglycaemic action. 
     
     
         15 . A method of reducing the activity of dipeptidyl peptidase IV or of dipeptidyl peptidase IV-analogous enzyme activities comprising a step of administering a pharmaceutically effective amount of a compound according to  claim 1 . 
     
     
         16 . A method for lowering the blood sugar level in the serum of a mammal below the glucose concentration that is characteristic of hyperglycaemia comprising a step of administering a pharmaceutically effective amount of a compound according to  claim 1 . 
     
     
         17 . A method for the oral treatment of metabolic disorders associated with diabetes mellitus comprising a step of administering a pharmaceutically effective amount of a compound according to  claim 1 . 
     
     
         18 . A method of treatment of impaired glucose tolerance, glycosuria, hyperlipidaemia, metabolic acidosis, diabetes mellitus, diabetic neuropathy and nephropathy and also of sequelae of diabetes mellitus in mammals comprising a step of administering a pharmaceutically effective amount of a compound according to  claim 1 .