New effectors of dipeptidylpeptidase iv

 

The invention relates to new effectors dipeptidylpeptidase IV - the dipeptide mimetics (I) formed from amino acids and thiazolidinone or pyrrolidino groups, namely: L-ALLO-isoleucyl-thiazolidine, L-ALLO-isoleucyl-pyrrolidino and their salts, salts of L-threo-isoleucyl-thiazolidine and L - threo-isoleucyl-pyrrolidine; a pharmaceutical composition having the ability to lower blood sugar, containing at least one of the above-mentioned compounds (1). 3 S. and 17 C.p. f-crystals, 4 Il., 3 table.

Description text in facsimile form (see graphic part).

Claims

1. Dipeptide mimetics formed from amino acids and thiazolidinone or pyrrolidino groups, namely L-ALLO-isoleucyl-thiazolidine, L-ALLO-isoleucyl-pyrrolidin and their salts.

2. Dipeptide mimetics under item 1, wherein the salt is an organic salt such as acetate, succinate, tartrate or fumarate, or contain inorganic acid residues, such as phosphate or sulfate.

3. Dipeptide mimetics one from p. 1 or 2, characterized in that they represent a salt with a molar ratio of dipeptide component and the sole is whether fumaric acid.

5. Dipeptide mimetics on p. 4, a salt of fumaric acid to L-ALLO-isoleucyl-thiazolidine.

6. Salts of dipeptide mimetics formed from amino acids and thiazolidinone or pyrrolidino groups, namely salts of L-threo-isoleucyl-thiazolidine and L-threo-isoleucyl-pyrrolidine.

7. Salt on p. 6, an organic salt.

8. Salt on p. 6, representing succinate, tartrate, fumarate and hydrochloride.

9. Pharmaceutical composition having the ability to reduce blood sugar, containing at least one compound according to one of the preceding paragraphs, if necessary in combination with one or more pharmaceutically acceptable carriers and/or diluents.

10. The pharmaceutical composition according to p. 9, characterized in that it contains a carrier for parenteral or enteral preparative forms.

11. The pharmaceutical composition according to p. 9, characterized in that it is a preparative form for oral administration.

12. The pharmaceutical composition according to one of paragraphs.9-11, characterized in that it additionally contains hypoglycemic active active substance.

13. Join one of the PP.1-8 for the preparation of Les is analogichnoi enzymatic activity.

14. Join one of the PP.1-8 for the preparation of drugs for lowering blood sugar with characteristic hyperglycemia glucose concentration in the serum of a mammal.

15. Join one of the PP.1-8 for the preparation of drugs for the treatment by oral administration of metabolic diseases associated with diabetes mellitus.

16. Join one of the PP.1-8 for the preparation of drugs for the treatment of impaired glucose tolerance, glycosuria, hyperlipemia, metabolic acidosis, diabetes mellitus, diabetic neuropathy and nephropathy, as well as caused by diabetes complications mammals.

17. The pharmaceutical composition according to one of paragraphs.9-12, which reduces the activity of the enzyme dipeptidylpeptidase IV or dipeptidyl peptidase IV-analogous enzymatic activity.

18. The pharmaceutical composition according to one of paragraphs.9-12 to reduce blood sugar when characteristic hyperglycemia glucose concentration in the serum of a mammal.

19. The pharmaceutical composition according to one of paragraphs.9-12 for the treatment by oral administration of metabolic diseases associated with diabetes mellitus.

is, hyperlipemia, metabolic acidosis, diabetes mellitus, diabetic neuropathy and nephropathy, as well as caused by diabetes complications mammals.

 

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where n=1-5;

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X=L or D-configuration;

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or pharmaceutically acceptable salt of this compound, where

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is a 5-8-membered monocyclic heterocyclic, optionally unsaturated ring containing from 1 to 4 heteroatoms selected from the group comprising N and S, and1selected from the group comprising SN, SN2, N, NH, O and S, provided that

< / BR>
is not pyrrolidinium when V represents NH;

A represents a group of the formula

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where Y1selected from the group comprising N-R2and R2means hydrogen; R2means hydrogen, R7when not with R2and R8mean hydrogen, alkyl, substituted alkoxy group, or R2together with R7form a 4 to 12-membered ring containing 2 nitrogen atom a heterocycle, optionally substituted by one or more substituents selected from the group comprising hydroxy, C1-C10< / BR>
where R2together with R7form a 5-8-membered ring containing two nitrogen atom a heterocycle, R5means hydrogen, R8means alkyl, optionally substituted by alkoxygroup; or A signifies a group

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< / BR>
in which Ar1denotes a heterocyclic group, which represents a pyrazole which may be substituted by one or more radicals R1, R2or R3; Ar2denotes phenyl, naphthyl or tetrahydronaphthyl, each of which optionally is substituted by one to three groups R2; L denotes a saturated or unsaturated, branched or unbranched carbon C1-C10chain; in which one or more methylene groups are optionally independently replaced by O, NH or S, and in which the linking group is optionally substituted by 0-2 of doxography; Q has a value selected from a range of: a) phenyl, naphthyl, pyridine, imidazole, Piran, etc. b) tetrahydropyran, morpholine, thiomorpholine, thiomorpholine and t

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