Novel GLP-1 Derivatives

A compound which has the formula (I):

• A-W—B—Y-therapeutic polypeptide (I)
• wherein:
• the therapeutic polypeptide is a GLP-1 peptide comprising the amino acid sequence of formula (V):
• Formula (V)
• (SEQ ID No:
• 3)
• Xaa7-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-
• Xaa18-Tyr-Leu-Glu-Xaa22-Xaa23-Ala-Ala-Xaa26-Glu-
• Phe-Ile-Xaa30-Trp-Leu-Val-Xaa34-Xaa35-Xaa36-
• Xaa37-Xaa38
• wherein
• Xaa7 is L-histidine, D-histidine, desamino-histidine, 2-amino-histidine, β-hydroxy-histidine, homohistidine, Nα-acetyl-histidine, α-fluoromethyl-histidine, α-methyl-histidine, 3-pyridylalanine, 2-pyridylalanine or 4-pyridylalanine;
• Xaa8 is Ala, Gly, Val, Leu, Ile, Lys, Aib, (1-aminocyclopropyl) carboxylic acid, (1-aminocyclobutyl) carboxylic acid, (1-aminocyclopentyl) carboxylic acid, (1-aminocyclohexyl) carboxylic acid, (1-aminocycloheptyl) carboxylic acid, or (1-aminocyclooctyl) carboxylic acid;
• Xaa18 is Ser, Lys or Arg;
• Xaa22 is Gly, Glu or Aib;
• Xaa23 is Gln, Glu, Lys or Arg;
• Xaa26 is Lys, Glu or Arg;
• Xaa30 is Ala, Glu or Arg;
• Xaa34 is Lys, Glu or Arg;
• Xaa35 is Gly or Aib;
• Xaa36 is Arg or Lys;
• Xaa37 is Gly, Ala, Glu or Lys;
• Xaa38 is Lys, amide or is absent;
• A is an albumin binding residue selected from the group consisting of:
• where the chiral carbon atom is either R or S,
• where the chiral carbon atom is either R or S,
• where the chiral carbon atom is either R or S,
• where the two chiral carbon atoms independently are either R or S,
• where the two chiral carbon atoms independently are either R or S,
• where the two chiral carbon atoms independently are either L or D,
• where the chiral carbon atom is either R or S,
• where the chiral carbon atom is either R or S,
• where the two chiral carbon atoms independently are either R or S,
• where the two chiral carbon atoms independently are either R or S,
• B is —(CH2)l—O—[(CH2)n—O]m—(CH2)p—[C(O)NH—(CH2)n—O—[(CH2)n—O]m—(CH2)p]q,
• where l, m, n, and p independently are 1-5, and q is 0-5,
• Y is a chemical group linking B and the therapeutic polypeptide, selected from the group consisting of —C(O)NH—, —NHC(O)—, —C(O)NHCH2—, —CH2NHC(O)—, —OC(O)NH —NHC(O)O—, —C(O)NHCH2—, CH2NHC(O)—, —C(O)CH2—, —CH2C(O)—, —C(O)CH═CH—, —CH═CHC(O)—, —(CH2)s—, —C(O)—, —C(O)O—, —OC(O)—, —NHC(O)— and —C(O)NH—, wherein s is 0 or 1, and
• W is a chemical group linking A and B, selected from the group consisting of —C(O)NH—, —NHC(O)—, —C(O)NHCH2—, —CH2NHC(O)—, —OC(O)NH —NHC(O)O—, —C(O)CH2—, —CH2C(O)—, —C(O)CH═CH—, —CH═CHC(O)—, —(CH2)s—, —C(O)—, —C(O)O—, —OC(O)—, —NHC(O)— and —C(O)NH—,
• wherein s is 0 or 1;
• or a pharmaceutically acceptable salt thereof.