Cyclopentapeptide derivatives and uses thereof

Patent metadata

Field	Value
Publication number	US-9266924-B2
Application number	US-201113641947-A
Country	US
Kind code	B2
Filing date	Apr 20, 2011
Priority date	Apr 20, 2010
Publication date	Feb 23, 2016
Grant date	Feb 23, 2016

Abstract

The present invention, among others, relates to a compound having a structure according to formula (I) or a pharmaceutically acceptable salt thereof, wherein Xaa 1 to Xaa 4 are independently of each other, an optionally N-alkylated natural or unnatural amino acid, R is H or methyl, L is a linker moiety, Ar is a spacer comprising an aromatic moiety, and D comprises, preferably is i) a combination of an organic complexation agent and a detectable label; or ii) a detectable label, an organic complexation agent or an active substance, said active substance particularly being selected from cytotoxic agents, lipids, sugars, sugar conjugates, sugar derivatives, proteins and combinations thereof, with the proviso that -L-Ar-D does not comprise a 18 F-benzoyl residue.

First claim

The invention claimed is:

1. A compound having a structure according to formula I

or a pharmaceutically acceptable salt thereof,
wherein Xaa 1 is D-tyrosine, Xaa 2 is arginine, Xaa 3 is naphthylalanine (Nal) and Xaa 4 is glycine,
R is methyl,
L has the formula —(CH 2 ) 3 —NH—, and
Ar is selected from the group consisting of

and D is
i) DOTA,
ii) a combination of a Ga atom and DOTA, or
iii) a combination of a Ga atom and DOTA, with the complexation agent DOTA being covalently bound to Ar.

2. The compound of claim 1 , wherein Ar is:

3. The compound of claim 1 , wherein the Ga atom is a radionuclide.

4. The compound of claim 1 , wherein the Ga atom is a Ga radionuclide.

5. A compound
i) having the structure:

wherein R is methyl
or

ii) having the structure:

wherein R is methyl.

6. A pharmaceutical composition comprising a compound as defined in claim 1 and at least one pharmaceutically acceptable excipient.

7. A diagnostic method
for the diagnosis of a CXCR4 receptor-related disease or disorder which comprises
contacting receptors in a patient with a compound of claim 1 ;
detecting the location and/or quantity of CXCR4 receptor in said patient by imaging the compound in the patient with a detectable label; and
correlating the location and/or quantity of the CXCR4 receptors to a CXCR4-related disease or disorder wherein the CXCR4-related disease or disorder is selected from the group consisting of multiple sclerosis (MS), lupus erythematosus, Sjögren's syndrome, ulcerative colitis, rheumatoid arthritis, atherosclerosis, thrombosis, asthma, Alzheimer's disease, vasculitis, HIV infection, benign and malignant tumors, myocardial infarction, and aneurysm.

8. A method of imaging CXCR4 receptors, which comprises contacting said receptors with a compound as defined in claim 1 , and detecting the compound of formula 1 with a detectable label wherein an image is generated.

9. A method of imaging CXCR4 receptor,
comprising administering a compound as defined in claim 1 to a sample or a subject and detecting the compound with a detectable label wherein an image is generated.

10. A method of imaging CXCR4 receptors, which comprises contacting said receptors with a composition as defined in claim 6 ; and detecting the compound of formula 1 with a detectable label wherein an image is generated.

11. The method of claim 10 , wherein the imaging is medical imaging.

12. The method of claim 11 , wherein the medical imaging is diagnostic imaging.

13. The compound of claim 3 , wherein the Ga atom is a non-radioactive isotope.

14. The compound of claim 3 , wherein the Ga atom is 66 Ga, 67 Ga or 68 Ga.

15. The method of claim 8 , wherein the imaging is medical imaging.

16. The method of claim 8 , wherein the medical imaging is diagnostic imaging.

17. The compound of claim 3 , wherein the Ga atom is a non-radioactive isotope selected from the group consisting of 66 Ga, 67 Ga or 68 Ga.

Assignees

• Demmer Oliver
• Kessler Horst
• Wester Hans-Jürgen
• Schottelius Margret
• Dijkgraaf Ingrid
• Buck Andreas Konard
• Univ Muenchen Tech

Inventors

• Demmer Oliver
• Kessler Horst
• Wester Hans-Jürgen
• Schottelius Margret
• Dijkgraaf Ingrid
• Buck Andreas Konard

Classifications

• C07K7/64 Primary

  Cyclic peptides containing only normal peptide links · CPC title

• A61K51/088

  conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10) · CPC title