Human glucagon-like-peptide-1 modulators and their use in...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 14/605 (2006.01)

Patent

CA 2571794

The present invention provides novel human glucagon-like peptide-1 (GLP-1)- receptor modulators that have biological activity similar or superior to native GLP-1 peptide and thus are useful for the treatment or prevention of diseases or disorders associated with GLP activity. Further, the present invention provides novel, chemically modified peptides that not only stimulate insulin secretion in type II diabetics, but also produce other beneficial insulinotropic responses. These synthetic peptide GLP-1 receptor modulators exhibit increased stability to proteolytic cleavage making them ideal therapeutic candidates for oral or parenteral administration. The peptides of this invention show desirable pharmacokinetic properties and desirable potency in efficacy models of diabetes.

Cette invention a pour objet l~introduction de nouveaux modulateurs de récepteurs de GLP-1 (glucagon-like-peptide-1) humain dont l~activité biologique est similaire ou supérieure à celle du GLP-1 natif et qui peuvent donc être utiles pour traiter ou prévenir certains troubles et maladies associés à l~activité du GLP-1. Cette invention propose également de nouveaux peptides chimiquement modifiés qui non seulement stimulent la sécrétion d~insuline dans les cas de diabète de type II mais provoquent aussi d~autres réactions insulinotropiques bénéfiques. Ces modulateurs synthétiques de récepteurs de GLP-1 démontrent une plus grande stabilité face au clivage protéolytique ce qui en fait des outils thérapeutiques de choix pour administration par voie orale ou parentérale. Les peptides proposés en vertu de l~invention possèdent des propriétés pharmacocinétique recherchées et démontrent un potentiel avantageux selon les modèles d~efficacité pour le diabète.

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