Connection unstable inhibitors dipeptidylpeptidase iv

 

The invention relates to compounds of unstable inhibitors dipeptidylpeptidase IV (DP IV), which have the General formula a-b-C, where a denotes an amino acid, A denotes a chemical bond between a and C or the amino acid and C indicates an unstable inhibitor of DP IV, namely the derived dipeptidylpeptidase, except derived peralkylated as derived dipeptidylpeptidase, the rest of peptidylglycine, dipeptidase or dipeptidylpeptidase. Effect: increase the stability of the inhibitors dipeptidylpeptidase IV, the possibility of regulation commencement and duration. These compounds are used for treatment of impaired glucose tolerance, glycosuria, hyperlipidemia, metabolic acidosis, diabetes mellitus, diabetic neuropathy and nephropathy, as well as due to diabetes complications mammals. Also described pharmaceutical compositions containing such compounds. 2 C. and 16 h.p. f-crystals, 8 ill., table 2.

Description text in facsimile form (see graphic part).

Claims

1. Connection inhibitors dipeptide a and C or the amino acid and C indicates an unstable inhibitor of DP IV, namely derived dipeptidylpeptidase, except derived peralkylated as derived dipeptidylpeptidase, as well as the remains of peptidylglycine, dipeptidase or dipeptidylpeptidase.

2. Connection on p. 1, characterized In that represents a Proline, hydroxyproline, thiazolidinediones acid, digitopolis, pipecolinic acid, azetidinone acid or aziridination acid.

3. Connection under item 1 or 2, characterized In that is a Proline or hydroxyproline.

4. Join one of the preceding paragraphs, wherein the dipeptide group represents Ile-Thia, Ile-Pyr, Val-Thia or Val-Pyr.

5. Join one of the preceding paragraphs, characterized in that the inhibitors are in salt form.

6. Join one of the preceding paragraphs, characterized in that the inhibitors are in the form of organic salts such as acetate, succinate, tartrate or fumarate, or in the form of inorganic acid residues, such as phosphate or sulfate.

7. Join one of the preceding paragraphs, characterized in that a-b is a dipeptide of the formula Ile-Pro or Gly-Pro.

8. Pharmaceutical to the and contains at least one compound according to one of the preceding paragraphs, if necessary, in combination with conventional carriers or excipients.

9. Join one of the PP.1-7 for the preparation of a medicine for an adjustable time inhibition in vivo DP IV.

10. Join one of the PP.1-7 for the cellular tissue or organ-specific inhibition of DP IV.

11. Join one of the PP.1-7 for the treatment of diseases of mammals, treatable by modulation of DP IV-activity.

12. Connection on p. 10 for treatment of metabolic diseases of the people.

13. Connection on p. 10 for the treatment of impaired glucose tolerance, glycosuria, hyperlipidemia, metabolic acidosis, diabetes mellitus, diabetic neuropathy and nephropathy, as well as due to diabetes complications mammals.

14. The pharmaceutical composition under item 8 for adjustable time inhibition in vivo DP IV.

15. The pharmaceutical composition under item 8 for cell tissue or organ-specific inhibition of DP - IV.

16. The pharmaceutical composition under item 8 for treatment of diseases of mammals, treatable by modulation of DP IV-activity.

17. The pharmaceutical composition according to p. 15 for the treatment of metabolic diseases of the people.

18. The pharmaceutical composition according to p. 15 for the treatment of impaired glucose tolerance, glycosuria, hyperlipid what's diabetes complications mammals.

 

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