| abstract |
The present invention relates to derivatives of GLP-1 analogues or pharmaceutically acceptable salts, amides or esters thereof, said analogues comprising corresponding to GLP-1 (7-37) (SEQ? ID? NO:? 1) The first K residue at position 18, the second K residue at another position, and compared with GLP-1 (7-37), the analog contains a maximum of 12 amino acid changes; the derivative contains two two extensions respectively connected to the first and second K residues via a linker, wherein the extensions are selected from Chem.1, Chem.2 and Chem.3: Chem.1: HOOC-(CH 2 ) x -CO-*Chem.2: HOOC-C 6 H 4 -O-(CH 2 ) y -CO-*Chem.3: R 2 -C 6 H 4 -(CH 2 ) z -CO-*, where x is an integer in the range of 6-18, y is an integer in the range of 3-17, z is an integer in the range of 1-5, and R2 is a molar mass not higher than 150? a group of Da; and the linker comprises Chem.4: *-NH-(CH 2 ) 2 -(O-(CH 2 ) 2 ) k -O-(CH 2 ) n -CO-*, wherein k is an integer in the range 1-5, and n is an integer in the range 1-5. The invention also relates to their pharmaceutical use, for example in the treatment and/or prevention of all forms of diabetes and related diseases, and to the corresponding novel peptides and side chain intermediates. Said derivatives are suitable for oral administration. |