| 摘要 |
The present invention relates to novel glucagon peptides with improved stability and solubility at neutral pH, to the use of the compounds in therapy, to methods of treatment comprising administration of the compounds to patients in need thereof, and to the use of the compounds in the manufacture of medicaments. The glucagon peptides of the invention are of particular interest in relation to the treatment of hyperglycemia, diabetes and obesity, as well as a variety of diseases or conditions associated with hyperglycemia, diabetes and obesity. |
| 主权项 |
1. A glucagon peptide derivative of formula [I]:
His-X2-X3-Gly-Thr-Phe-Thr-Ser-Asp-X10-Ser-X12-Tyr-Leu-X15-X16-Arg-X18-Ala-X20-X21-Phe-Val-X24-Trp-Leu-X27-X28-X29-X30 [I] comprising a substituent attached to a nitrogen of a side chain of an amino acid selected from the group consisting of positions X12, X16, X20, X21, X24, X28, X29, and X30 of said glucagon peptide, and wherein said substituent comprises formula II:
Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12 [II] wherein Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8, Y9, Y10 and Y11 are individually absent, individually represent an amino acid or i, ii, iii, iv, which have the stereochemistry L or D, or the structure v:and,
Y12 is absent or represents a C2-6 acyl group or a succinoyl moiety provided that the substituent of formula II contains between three and ten negatively charged moieties, or a pharmaceutically acceptable salt, amide or carboxylic acid thereof. |
