N-terminal modified FGF21 compounds

Patent metadata

Field	Value
Publication number	US-9655974-B2
Application number	US-201113809273-A
Country	US
Kind code	B2
Filing date	Jul 18, 2011
Priority date	Jul 20, 2010
Publication date	May 23, 2017
Grant date	May 23, 2017

Abstract

Analogs of FGF21 carrying a modifying, substituted ethylene or benzyl group can be used for treatment or prevention of diabetes, dyslipidemia, obesity, cardiovascular diseases, metabolic syndrome, and/or Non Alcoholic Fatty Liver Disease (NAFLD).

First claim

What is claimed is:

1. A compound comprising an FGF21 polypeptide or an analogue thereof, derivatized with A-B-C-D- covalently attached to the alpha amino-group of the N-terminal amino acid of the FGF21 polypeptide (SEQ ID NO:1) or an analogue thereof, wherein the FGF21 analogue has at least 80% identity to SEQ ID NO:1; and wherein:
A- is an element of formula I:

wherein n is 12, 14, or 16, and * is the point of attachment to -B-,
-B- is an element of formula VIII

wherein b is 2, c is 0, * is the point of attachment to -C-, and # is the point of attachment to A-;
-C- is an element of formula XI:

wherein p is 1, q is 2, * is the point of attachment to -D-, and # is the point of attachment to -B-;
-D- is an element of formula XIV:

wherein s is 1, * is the point of attachment to the FGF21 polypeptide or an analogue thereof and # is the point of attachment to -C-;
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein A-B-C-D- is selected from the group consisting of:

3. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

4. The compound of claim 1 , wherein the FGF21 analogue is a Gly-FGF21 analogue consisting of a Lysine (K) to Arginine (R) substitutions at residues 56, 59, 69 and 122 of the native FGF21 polypeptide (SEQ ID NO:1).

Assignees

• Tagmose Tina Moeller
• Garibay Patrick William
• Zhang Xujia
• Thoegersen Henning
• Nielsen Peter Kresten
• Bak-Jensen Kristian Sass
• Woeldike Helle Fabricius
• Novo Nordisk As

Inventors

• Tagmose Tina Moeller
• Garibay Patrick William
• Zhang Xujia
• Thoegersen Henning
• Nielsen Peter Kresten
• Bak-Jensen Kristian Sass
• Woeldike Helle Fabricius

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title