Cyclodecapeptide compounds for use as drugs

Patent metadata

Field	Value
Publication number	US-9856294-B2
Application number	US-201113698450-A
Country	US
Kind code	B2
Filing date	May 17, 2011
Priority date	May 17, 2010
Publication date	Jan 2, 2018
Grant date	Jan 2, 2018

Abstract

The invention relates to novel cyclodecapeptide compounds having formula (I) for use as drugs and, more specifically, for use in the diagnosis, prevention and/or treatment of neurodegenerative diseases, such as Wilson's disease and Alzheimer's disease, and for use in the diagnosis, prevention and/or treatment of poisoning with metal ions, such as copper and mercury ions. The invention also relates to pharmaceutical compositions comprising at least one compound having formula (I) as an active principle.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising:
at least one cyclodecapeptide compound corresponding to the following formula

(I):
in which:
the cysteine amino acids Cys 2 and Cys 7 may or may not be linked by a covalent bond Cys 2 -Cys 7 via their sulfur atoms,

X 1 , X 3 , X 4 , X 5 , X 6 , X 8 , X 9 and X 10 , which are identical or different, are amino acids present in their dextrorotary (D) or levorotary form (L),
n 1 , n 3 , n 6 , and n 8 , which are identical or different, are equal to 0 or 1, and wherein at least one of n t , n 3 , n 6 , and n 8 must be equal to 1,
Y 1 , Y 3 , Y 6 , and Y 8 , which are identical or different, represent groups —C(O)—CHNL, —C(O)EL or —NHEL, in which L is a ligand for hepatic or neuronal cells, and E is a spacer arm selected from polyols and optionally substituted alkyl chains having 1 to 12 carbon atoms, and wherein at least one of the groups herein at least one of the groups Y 1 , Y 3 , Y 6 , and Y 8 represents a group —C(O)CHNL,
wherein the dipeptide sequences X 4 -X 5 and X 9 -X 10 , which are identical or different, are chosen from the dipeptides (D)Pro-(L)X or (L)Pro-(D)X′, in which X and X′ are amino acids, and
at least one pharmaceutically acceptable vehicle,
optionally, one of the amino acids X 4 , X 5 , X 9 , and X 10 , or one of the groups Y 1 , Y 3 , Y 6 , and Y 8 , may be substituted with a group selected from: —CO-fluorophore, —NH-fluorophore, —C(S)NH-fluorophore, —SO2-fluorophore, ═CH-fluorophore and -E′-fluorophore, where E′ is a spacer arm selected from phenyl and triazole.

2. The compound as claimed in claim 1 , wherein at least one of the amino acids X 1 , X 3 , X 6 , and X 8 is a lysine.

3. The compound as claimed in claim 1 , wherein X and X′ are chosen from glycine, lysine, glutamate or aspartate.

4. The compound as claimed in claim 1 , wherein the ligand L for hepatic or neuronal cells is selected from monosaccharides.

5. The compound as claimed in claim 1 , wherein the fluorophore is selected from the group consisting of rhodamine, fluorescein, pyronin, coumarin, benzophenone, anthrone, fluorenone, pyridine, quinoleine, acridine, naphthalene, anthracene, naphthacene, pentacene and xanthene.

6. The compound as claimed in claim 1 , wherein one of the amino acids X 4 , X 5 , X 9 , and X 10 , or one of the groups Y 1 , Y 3 , Y 6 , and Y 8 is substituted with a group selected from the group consisting of —CO-fluorophore, —NH-fluorophore, —C(S)NH-fluorophore, —SO2-fluorophore, ═CH-fluorophore, and E′-fluorophore.

7. The compound as claimed in claim 1 , wherein at least one of the amino acids X 1 , X 3 , X 6 , and X 8 is a lysine bearing a group Y 1 , Y 3 , Y 6 and Y 8 .

8. A method for the treatment of Wilson's disease or for the treatment of Alzheimer's disease comprising the step of administering the cyclodecapeptide compound corresponding to the following formula (I) of claim 1 to a patient in need thereof.

9. A method for the diagnosis or treatment of poisoning with metal ions comprising the step of administering the compounds of claim 1 to a patient in need thereof.

10. The method as claimed in claim 9 , wherein the patient has been poisoned with copper ions or mercury ions.

11. The method as claimed in claim 9 , wherein the metal ion is selected from the group consisting of silver, cadmium, cobalt, copper, mercury, nickel, gold, lead and zinc ions.

12. The compound as claimed in claim 4 , wherein the monosaccharide is selected from the group consisting of glucose, galactose and N-acetylgalactosamine.

Assignees

• Delangle Pascale
• Pujol Anaïs
• Dumy Pascal
• Renaudet Olivier
• Ferrand Michel
• Commissariat Energie Atomique
• Univ Joseph Fourier

Inventors

• Delangle Pascale
• Pujol Anaïs
• Dumy Pascal
• Renaudet Olivier
• Ferrand Michel

Classifications

• A61P39/04

  Chelating agents · CPC title

• C07K7/64

  Cyclic peptides containing only normal peptide links · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• C07K9/006 Primary

  the peptide sequence being part of a ring structure · CPC title

• A61K49/0056

  Peptides, proteins, polyamino acids · CPC title