Derivatives of GLP-1 analogs

A glucagon-like peptide 1(GLP-1) derivative of formula I:

• 7 8 9 10 11 12 13 14 15 16 17
• Xaa-Xaa-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-
• 18 19 20 21 22 23 24 25 26 27 28
• Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Phe-
• 29 30 31 32 33 34 35 36 37 38 39
• Ile-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa
• wherein
• Xaa at position 7 is His, a modified amino acid, or is deleted
• Xaa at position 8 is Ala, Gly, Ser, Thr, Leu, Ile, Val, Glu, or Asp,
• Xaa at position 18 is Ser, Ala, Gly, Thr, Leu, Ile, Val, Glu, Asp, or Lys,
• Xaa at position 19 is Tyr, Phe, Trp, Glu, Asp, or Lys,
• Xaa at position 20 is Leu, Ala, Gly, Ser, Thr, Leu, Ile, Val, Glu, Asp, or Lys,
• Xaa at position 21 is Glu, Asp, or Lys,
• Xaa at position 22 is Gly, Ala, Ser, Thr, Leu, Ile, Val, Glu, Asp, or Lys,
• Xaa at position 23 is Gln, Asn, Arg, Glu, Asp, or Lys,
• Xaa at position 24 is Ala, Gly, Ser, Thr, Leu, Ile, Val, Arg, Glu, Asp, or Lys,
• Xaa at position 25 is Ala, Gly, Ser, Thr, Leu, Ile, Val, Glu, Asp, or Lys,
• Xaa at position 26 is Lys, Arg, Gln, Glu, Asp, or His,
• Xaa at position 27 is Glu, Asp, or Lys,
• Xaa at position 30 is Ala, Gly, Ser, Thr, Leu, Ile, Val, Glu, Asp, or Lys,
• Xaa at position 31 is Trp, Phe, Tyr, Glu, Asp, or Lys,
• Xaa at position 32 is Leu, Gly, Ala, Ser, Thr, Ile, Val, Glu, Asp, or Lys,
• Xaa at position 33 is Val, Gly, Ala, Ser, Thr, Leu, Ile, Glu, Asp, or Lys,
• Xaa at position 34 is Lys, Arg, Glu, Asp, or His,
• Xaa at position 35 is Gly, Ala, Ser, Thr, Leu, Ile, Val, Glu, Asp, or Lys,
• Xaa at position 36 is Arg, Lys, Glu, Asp, or His,
• Xaa at position 37 is Gly, Ala, Ser, Thr, Leu, Ile, Val, Glu, Asp, or Lys or is deleted
• Xaa at position 38 is Arg, Lys, Glu, Asp, or His, or is deleted,
• Xaa at position 39 is Arg or is deleted,
• or
• (a) a C-1-6-ester thereof, (b) amide, C-1-6-alkylamide, or C-1-6-dialkylamide thereof and/or (c) a pharmaceutically acceptable salt thereof, provided that
• (i) when the amino acid at position 37 or 38 is deleted, then each amino acid downstream of the amino acid is also deleted,
• (ii) the GLP-1 derivative contains only one Lys and the Lys is not the N-terminal or C-terminal amino acid of the derivative,
• (iii) a lipophilic substituent of from 12 to 25 carbons is attached, optionally via a spacer, to the ε-amino group of the Lys, and
• the total number of different amino acids between the GLP-1 derivative and the corresponding native form of GLP- 1 does not exceed five.