| 主权项 |
1. A compound having the formula:
R1—P1—P2—R2 wherein
R1 is H, C1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl; R2 is OH or NH2; P1 is a peptide having the sequence:H-X2-X3-GTFTSDYSKYLDSΨAAHDFVEWLLSAwherein:X2 is selected from Aib, Ala, D-Ala, Ser, N-Me-Ser, Ac3c, Ac4c and Ac5c;X3 is selected from Gln and His;
P2 is absent or is a sequence of 1-20 amino acid units independently selected from the group consisting of Ala, Leu, Ser, Thr, Tyr, Cys, Glu, Lys, Arg, Dbu, Dpr and Orn;or a pharmaceutically acceptable salt or solvate thereof;
Ψ is a residue of Lys, Arg, Orn or Cys in which the side chain is conjugated to a substituent having the formula -Z2-Z1; -Z1 is a fatty chain having a polar group at one end of the chain and a connection to Z2, —X— at the end of the chain distal from the polar group,wherein the polar group comprises a carboxylic acid or a carboxylic acid bioisostere, a phosphonic acid, or a sulfonic acid group;and —X— is a bond, —CO—, —SO—, or —SO2—;
-Z2- is a spacer of formula:wherein:each Y is independently —NH, —NR, —S or —O, where R is alkyl, a protecting group or forms a linkage to another part of the spacer Z2;each X is independently a bond, CO—, SO—, or SO2—;with the proviso that when Y is S, X is a bond;each V is independently a bivalent organic moiety linking Y and X;and n is 1-10;or a pharmaceutically acceptable salt or solvate thereof. |
