| 摘要 |
The present invention relates to amylin analogues and to their use in the treatment or prevention of a variety of diseases, conditions or disorders, including obesity, excess food intake and associated metabolic diseases such as diabetes. The analogues have good physical and chemical stability, good solubility, and a long duration of action, and are well suited for use in the form of a liquid formulation. |
| 主权项 |
1. An amylin analogue which is a compound having the formula:
R1—Z—R2 wherein R1 is hydrogen, C1-4 acyl, benzoyl or C1-4 alkyl, or a half-life extending moiety M, wherein M is optionally linked to Z via a linker moiety L; R2 is OH or NHR3, wherein R3 is hydrogen or C1-3-alkyl; and Z is an amino acid sequence of formula I:(I)(SEQ ID NO: 3)Arg-Cys-X3-Thr-Ala-Thr-Cys-Ala-Thr-X10-Arg-Leu-Ala-X14-Phe-Leu-X17-Arg-X19-X20-Phe-Gly(Me)-Ala-Ile(Me)-Leu-Ser-Ser-Thr-X31-Val-Gly-Ser-X35-Thr- X37; wherein X3 is selected from the group consisting of Asn, Gly, Pro and Gln; X10 is selected from the group consisting of Gln, Asp and Glu; X14 is selected from the group consisting of Asp, His, Asn and Aad; X17 is selected from the group consisting of His, Asn, Gln, Glu, Thr, Val, Lys and Aad; X19-X20 is selected from the group consisting of Ser-Ser, Val-Val, Ser-Val and Val-Ser, or is absent; X31 is selected from the group consisting of Asp, Glu and Asn; X35 is selected from the group consisting of Asp, Glu, Asn, Ser, Phe, Orn, Aad, Gly and Thr; and X37 is selected from the group consisting of Pro, Apr and Hyp; and wherein the compound has at least one residue selected from: X3 is Gln; X14 is His, Asn or Aad; X17 is Asn, Gln, Glu, Thr or Aad; X19-X20 is Val-Ser or Ser-Val; and X35 is Ser, Phe, Orn, Aad, Gly or Thr; or a pharmaceutically acceptable salt or solvate thereof. |
