| abstract |
The present invention relates to derivatives of GLP-1 analogues comprising position 18 corresponding to GLP-1(7-37) (SEQ ID NO: 1) or pharmaceutically acceptable salts, amides or esters thereof The first K residue of , 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 An extension linked to said first and second K residues, respectively, wherein said extension is selected from Chem.1, Chem.2 and Chem.3: Chem.1: HOOC-(CH 2 ) x -CO- *; Chem.2: HOOC- C6H4 - O- ( CH2 ) y -CO-*; Chem.3: R2 - C6H4- ( CH2 ) 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 R is a group with a molar mass not higher than 150Da; and the linker comprises Chem.4 : *-NH-(CH 2 ) 2 -(O-(CH 2 ) 2 ) k -O-(CH 2 ) n -CO-*, where k is an integer in the range 1-5, and n is 1- An integer in the range of 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. |