| abstract |
The present invention relates to GLP-1 receptor agonist compounds having a modified N-terminus. The compound has the formula Chem.1: YZP, where P represents a fragment of a GLP-1 receptor agonist peptide lacking two N-terminal amino acid residues and YZ is a novel His-Ala mimetic Represents a compound. Examples of GLP-1 receptor agonist compounds are derived from human GLP-1 (7-37), exendin-4 (1-39) or GLP-1A (1-37). The present invention also relates to derivatives of these compounds, particularly those having one or more albumin binding side chains that are capable of sustaining the duration of action of these compounds in vivo. The peptides and derivatives of the present invention have good potency, sustained pharmacokinetic profile, are stable to degradation by gastrointestinal enzymes, and / or have high oral bioavailability. These properties are important in the development of GLP-1 receptor agonist compounds for subcutaneous administration, intravenous administration, and / or especially oral administration. The invention also relates to intermediate products for use in the preparation of the GLP-1 receptor agonist compounds of the invention. |