Peptide conjugates of GLP-1 receptor agonists and gastrin and their use

摘要

The present invention relates, inter alia, to certain peptide conjugates, and to the use of the conjugates in the treatment of a variety of diseases or disorders, including diabetes (type 1 and/or type 2) and diabetes-related diseases or disorders.

主权项

1. A peptide conjugate or pharmaceutically acceptable salt thereof having the formula
R1—Za-La-Ya—R2  (I) wherein R1 is H, C1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl; R2 is OH or NH2; Za is a peptide sequence having the formula IVa
His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Z9-Leu-Ser-Z12-Gln-Met-Glu-Z16-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Z27-Z28  (IVa) wherein Z9 is selected from Glu and Asp; Z12 is selected from Lys and Orn; Z16 is selected from Glu and Lys; Z27 is selected from Lys and Orn; Z28 is selected from Asn and Asp or is absent; La is a sequence having the formula IVb
L1-L2-L3-L4  (IVb) wherein L1 is selected from Peg3, Gln, Cys, Lys and Orn or is absent; L2 is selected from Peg3, Gln, Cys, Lys and Orn or is absent; L3 is selected from Peg3, Gln, Cys, Lys and Orn or is absent; L4 is selected from Peg3, Gln, Cys, Lys and Orn or is absent; Ya is a peptide sequence having the formula IVc
Y12-Y13-Trp-Leu-Asp-Phe  (IVc) wherein Y12 is Tyr or is absent; and Y13 is Gly or is absent.