A4B7 peptide monomer and dimer antagonists

Patent metadata

Field	Value
Publication number	US-9518091-B2
Application number	US-201615046325-A
Country	US
Kind code	B2
Filing date	Feb 17, 2016
Priority date	Oct 1, 2014
Publication date	Dec 13, 2016
Grant date	Dec 13, 2016

Abstract

The invention relates to peptide dimer compounds and peptide monomer compounds that potently inhibit binding of α4β7 to the mucosal addressin cell adhesion molecule (MAdCAM) in vivo, possess high selectivity against α4β1 binding, and have high stability under gastrointestinal conditions.

First claim

The invention claimed is:

1. A peptide comprising the amino acid sequence:
Pen-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β-homo-Glu)-(D-Lys).

2. The peptide of claim 1 , comprising a disulfide bond between the two Pen amino acids.

3. The peptide of claim 1 , further comprising a linker moiety.

4. The peptide of claim 3 , wherein the linker moiety is bound to the D-Lys amino acid.

5. The peptide of claim 4 , wherein the linker moiety is diglycolic acid (DIG).

6. The peptide of claim 1 , wherein the N-terminus of the peptide is acylated.

7. The peptide of claim 1 , comprising a C-terminal free amide.

8. The peptide of claim 1 , comprising a disulfide bond between the two Pen amino acids and a linker moiety bound to the D-Lys amino acid, wherein the N-terminus of the peptide is acylated.

9. A peptide dimer compound comprising two peptides, each peptide comprising the amino acid sequence:
Pen-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β-homo-Glu)-(D-Lys), or a pharmaceutically acceptable salt thereof,
wherein the two peptides are linked by a linker moiety.

10. The peptide dimer compound of claim 9 , wherein the linker moiety is bound to the D-Lys amino acids of the two peptides.

11. The peptide dimer compound or pharmaceutically acceptable salt thereof of claim 9 , wherein the linker moiety is diglycolic acid (DIG).

12. The peptide dimer compound or pharmaceutically acceptable salt thereof of claim 9 , wherein each of the two peptides comprises a disulfide bond between the two Pen amino acids.

13. The peptide dimer compound or pharmaceutically acceptable salt thereof of claim 9 , wherein the N-terminus of each of the two peptides is acylated.

14. The peptide dimer compound or pharmaceutically acceptable salt thereof of claim 9 , wherein each of the two peptides comprises a C-terminal free amide.

15. The peptide dimer compound or pharmaceutically acceptable salt thereof of claim 9 , where each of the two peptides comprises a disulfide bond between the two Pen amino acids and wherein the N-terminus of each of the two peptides is acylated.

16. The peptide dimer compound or pharmaceutically acceptable salt thereof of claim 9 , having the structure:

17. The peptide dimer compound or pharmaceutically acceptable salt thereof of claim 9 , wherein the peptide dimer compound or pharmaceutically acceptable salt thereof is an acetate salt of the peptide dimer compound.

18. A pharmaceutical composition comprising the peptide dimer compound of claim 9 and a pharmaceutically acceptable excipient, carrier or diluent.

19. The pharmaceutical composition of claim 18 , wherein the peptide dimer compound has the structure:

20. The pharmaceutical composition of claim 19 , wherein the peptide dimer compound or pharmaceutically acceptable salt thereof is an acetate salt of the peptide dimer compound.

21. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition comprises an enteric coating.

Assignees

• Protagonist Therapeutics Inc

Inventors

• Bhandari Ashok
• Patel Dinesh V
• Zemede Genet
• Mattheakis Larry C
• Liu David

Classifications

• A61P43/00

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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title