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1. (WO2019030268) AGONISTES DU RÉCEPTEUR DE GLP-1/GLUCAGON DANS LE TRAITEMENT DE LA STÉATOSE HÉPATIQUE ET DE LA STÉATOHÉPATITE
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

Claims

1 . A compound or salt or solvate thereof having the general formula A

His-(D-Ser)-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-X14-X15- X16-X17-X18-Ala-X20-Asp-Phe-lle-Glu-Trp-Leu-Lys-X28-Gly-Gly-Pro- Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2

wherein

X14 is Lys, wherein the -NH2 side chain group is functionalized by one of the groups selected from (S)-4-Carboxy-4-hexadecanoylamino-butyryl- (γΕ-Palm) and (S)-4-Carboxy-4-octadecanoylamino-butyryl- (γΕ-Stea); X15 is Asp or Glu;

X16 is Ser or Glu;

X17 is Lys, Arg, or Gin;

X18 is Ala, Arg or Leu;

X20 is Gin or Lys; and

X28 is Ala or Asn;

for use in a method of preventing and/or treating metabolic liver disease.

2. The compound or salt or solvate thereof of claim 1 for use according to claim 1 , wherein

X14 is Lys, wherein the -NH2 side chain group is functionalized by one of the groups selected from (S)-4-Carboxy-4-hexadecanoylamino-butyryl- (γΕ-Palm) and (S)-4-Carboxy-4-octadecanoylamino-butyryl- (γΕ-Stea); X15 is Asp or Glu;

X16 is Ser or Glu;

X17 is Lys or Gin;

X18 is Ala or Leu;

X20 is Gin or Lys; and

X28 is Ala.

The compound or salt or solvate thereof of claim 1 for use according to claim 1 , wherein

X14 is Lys, wherein the -NH2 side chain group is functionalized by (S)-4- Carboxy-4-hexadecanoylamino-butyryl- (γΕ-Palm);

X15 is Asp or Glu;

X16 is Ser;

X17 is Lys or Arg;

X18 is Ala or Arg;

X20 is Gin; and

X28 is Ala or Asn.

The compound or salt or solvate thereof of claim 1 for use according to claim 1 , wherein the compound is any one of SEQ ID NO.: 1 , SEQ ID NO.: 2 or SEQ ID NO.: 3, or a salt or solvate thereof.

The compound or salt or solvate thereof of any one of claims 1 -4 for use according to any one of claims 1 -4, wherein said compound has a high solubility at an acidic pH, particularly between 3.5 and 5.5, more particularly about 4.5, and/or a physiological pH, particularly about 7.4, and wherein said solubility at said acidic and/or physiological pH is at least 0.5 mg/ml.

6. A pharmaceutical composition comprising a compound or salt or solvate thereof of any one of claims 1 -5 as an active agent together with at least one pharmaceutically acceptable carrier, for use according to claim 1 .

7. The pharmaceutical composition of claim 6 for use according to claim 1 , wherein the pharmaceutical composition is parenterally administered, particularly injected.

8. The pharmaceutical composition of claim 6 or 7 for use according to claim 1 , wherein the pharmaceutical composition is administered in combination with at least one further therapeutically active ingredient.

9. The compound or salt or solvate thereof of any one of claims 1 -5 or the pharmaceutical composition of any one of claims 6-8 for use in a method of preventing and/or treating non-alcoholic fatty liver disease (NAFLD), particularly non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis

(NASH) and/or NAFLD-associated liver fibrosis.

10. The compound or salt or solvate thereof of any one of claims 1 -5 or the pharmaceutical composition of any one of claims 6-8 for use in a method of preventing and/or treating non-alcoholic steatohepatitis (NASH), particularly NASH associated with fibrosis.

1 1 . The compound or salt or solvate thereof of any one of claims 1 -5 or the pharmaceutical composition of any one of claims 6-8 for use in a method of preventing and/or treating sequelae of non-alcoholic steatohepatitis

(NASH), particularly NAFLD-related liver cirrhosis and/or NAFLD-related hepatocellular carcinoma.

12. The compound or salt or solvate thereof of any one of claims 1 -5 or the pharmaceutical composition of any one of claims 6-8 for use in a method of simultaneously preventing and/or simultaneously treating NASH and additional pathological conditions or risk factors, particularly obesity and/or type 2 diabetes mellitus.

13. A method of preventing or treating metabolic liver disease in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound or salt or solvate thereof having the general formula A

His-(D-Ser)-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-X14-X15- X16-X17-X18-Ala-X20-Asp-Phe-lle-Glu-Trp-Leu-Lys-X28-Gly-Gly-Pro- Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2

wherein

X14 is Lys, wherein the -NH2 side chain group is functionalized by one of the groups selected from (S)-4-Carboxy-4-hexadecanoylamino-butyryl-(γΕ-Palm) and (S)-4-Carboxy-4-octadecanoylamino-butyryl- (yE-Stea); X15 is Asp or Glu;

X16 is Ser or Glu;

X17 is Lys, Arg, or Gin;

X18 is Ala, Arg or Leu;

X20 is Gin or Lys; and

X28 is Ala or Asn.