Dual Agonist Compound

Claims

1. A dual GLP-1 / MHC agonist compound having the structure of Formula I: His-Aib-Gln-Gly-Thr-AA1-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Glu-Lys-Lys-Ala-Lys((CO(CH2) n1 PEG n2 ) n3 -(AA2) n4 -CO(CH2) n5 -COOH)-Glu-Phe-Val-Glu-Trp-Leu-Leu-Glu-(5-Ava)-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-AA3 Formula I Where: AA1 is selected from the group consisting of Phe, αMePhe and αMePhe (2F); AA2 is selected from the group consisting of γGlu, δAad, εApm and ζAsu; AA3 is selected from the group consisting of amino and hydroxyl; n1=1-5, n2=1-30, n3=0 or n3=1-5, n4=0 or n4=1-5 and n5=10-30.

2. The GLP-1 / MHC dual agonist compound of claim 1, wherein AA1 is Phe, AA2 is γGlu, AA3 is an amine, n1=1-5, n2=1-30, n3=0 or n3=1-5, n4=0 or n4=1-5, and n5=10-30.

3. The GLP-1 / MHC dual agonist compound of claim 2, wherein AA1 is Phe, AA2 is γGlu, AA3 is an amine, n1=1, n2=5, n3=1, n4=1, and n5=18.

4. The GLP-1 / MHC dual agonist compound of claim 1, wherein AA1 is αMePhe, AA2 is γGlu, AA3 is amino, n1=1-5, n2=1-30, n3=0 or n3=1-5, n4=0 or n4=1-5, and n5=10-30.

5. The dual GLP-1 / MHC agonist compound of claim 4, wherein AA1 is αMePhe, AA2 is γGlu, AA3 is amino, n1=1, n2=5, n3=1, n4=1, and n5=18.

6. The GLP-1 / MHC dual agonist compound of claim 1, wherein AA1 is αMePhe, AA2 is δAad, AA3 is amino, n1=1-5, n2=1-30, n3=0 or n3=1-5, n4=0 or n4=1-5, and n5=10-30.

7. The dual GLP-1 / MHC agonist compound of claim 6, wherein AA1 is αMePhe, AA2 is δAad, AA3 is amino, n1=1, n2=5, n3=1, n4=1, and n5=18.

8. The GLP-1 / MHC dual agonist compound of claim 1, wherein AA1 is αMePhe (2F), AA2 is γGlu, AA3 is amino, n1=1-5, n2=1-30, n3=0 or n3=1-5, n4=0 or n4=1-5, and n5=10-30.

9. The dual GLP-1 / MHC agonist compound of claim 8, wherein AA1 is αMePhe (2F), AA2 is γGlu, AA3 is amino, n1=1, n2=5, n3=1, n4=1, and n5=18.

10. The GLP-1 / MHC dual agonist compound of claim 1, wherein AA1 is αMePhe (2F), AA2 is δAad, AA3 is amino, n1=1-5, n2=1-30, n3=0 or n3=1-5, n4=0 or n4=1-5, and n5=10-30.

11. The dual GLP-1 / MHC agonist compound of claim 10, wherein AA1 is αMePhe (2F), AA2 is δAad, AA3 is amino, n1=1, n2=5, n3=1, n4=1, and n5=18.

12. A dual GLP-1 / MHC agonist compound according to any one of claims 1 to 11, wherein the compound has: (I) the amino acid sequence shown in any one of SEQ ID NOs: 2-16; (II) an amino acid sequence obtained by substitution, deletion or addition of 1, 2, 3 or more amino acids in the amino acid sequence (I) and having the same function as the amino acid sequence (I); or (III) an amino acid sequence having 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or greater sequence identity to the amino acid sequence of (I) or (II).

13. A dual GLP-1 / MHC agonist compound according to any one of claims 1 to 12, wherein the dual agonist compound comprises a pharmaceutically acceptable salt, solvate, chelate, or non-covalent complex formed by the compound, a precursor of the compound, or any mixture thereof.

14. Use of a dual GLP-1 / MHC agonist compound according to any one of claims 1 to 13 in the manufacture of a pharmaceutical composition for the treatment of a disease.

15. The use according to claim 14, wherein the pharmaceutical composition is intended for use in the manufacture of a medicinal product for the treatment of at least one of the diseases comprising type II diabetes, impaired glucose tolerance, type I diabetes, obesity, arterial hypertension, metabolic syndrome, dyslipidemia, cognitive impairment, atherosclerosis, myocardial infarction, coronary heart disease, cardiovascular disease, stroke, inflammatory bowel syndrome and / or dyspepsia or gastric ulcer, liver fibrosis and pulmonary fibrosis.

16. A medicinal product comprising a dual GLP-1 / MHC agonist compound according to any one of claims 1 to 13.

17. A pharmaceutical composition comprising a dual GLP-1 / MHC agonist compound according to any one of claims 1 to 13 and any additional active ingredient.

18. A method for treating a disease, comprising administering a dual GLP-1 / MHC agonist compound according to any one of claims 1-13, a medicinal product according to claim 16, or a pharmaceutical composition according to claim 17.