Radioactively labelled amino acid analogues, their preparation and use

• US 20060127306A1
• Filed: 08/01/2003
• Published: 06/15/2006
• Est. Priority Date: 08/02/2002
• Status: Active Grant

• Current Assignee: Vrije Universiteit Brussel
• Original Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Inventors: Mertens, John J.R.
• Granted Patent: US 7,189,383 B2
• Time in Patent Office: Days
• US Class Current: 424/1.110
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 49/0438 Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol
• CPC Class Codes: A61K 51/0406 Amines, polyamines, e.g. spermine, spermidine, amino acids, (bis)guanidines
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention relates to Halogenated amino acid analogues for use in diagnosis, which compounds have the genera formula (I) wherein: R is (C₁-C₆) alkyl optionally substituted with thioether or ether oxygen atom when n=0, or a substituted aromatic or heteraromatic ring when n=1-6; and m=0 or 1; and X is a halogen atom. The invention further relates to precursor compounds for these analogues, to a method of preparing these analogues, to a pharmaceutical composition comprising these analogues and to the use of these analogues and compositions in the diagnosis of cancer.

Claims

1. A halogenated amino acid analogue having the general formula:

2. The analogue of claim 1, wherein R is methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl or methyl thioethyl.

3. The analogue of claim 1, wherein R is phenyl, hydroxyphenyl, pyridyl or hydroxypyridyl.

9. The analogue of claim 1, wherein the analogue is selected from the group consisting of:

[¹⁸F] labeled L,D-2-amino-3-(2-fluoromethyl-phenyl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(3-fluoromethyl-phenyl)-propionic acid;

[¹⁸F labeled L,D-2-amino-3-(4-fluoromethyl-phenyl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(2-fluoroethyl-phenyl) propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(3-fluoroethyl-phenyl)propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(4-fluoroethyl-phenyl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(3-fluoromethyl-pyridin-2-yl)propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(4-fluoromethyl-pyridin-2-yl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(5-fluoromethyl-pyridin-2-yl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(6-fluoromethyl-pyridin-2-yl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(3-fluoroethyl-pyridin-2-yl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(4-fluoroethyl-pyridin-2-yl)-propionic acid;

(¹⁸F] labeled L,D-2-amino-3-(5-fluoroethyl-pyridin-2-yl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(6-fluoroethyl-pyridin-2-yl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(2-fluoromethyl-4-hydroxy-phenyl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(5-fluoromethyl-3-hydroxy-phenyl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(6-fluoromethyl-3-hydroxy-phenyl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(2-fluoroethyl-4-hydroxy-phenyl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(5-fluoroethyl-3-hydroxy-phenyl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(6-fluoroethyl-3-hydroxy-phenyl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(3-fluoromethyl-5-hydroxy-pyridin-2-yl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(3-fluoroethyl-5-hydroxy-pyridin-2-yl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(3-fluoromethyl-6-hydroxy-pyridin-2-yl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(4-fluoromethyl-6-hydroxy-pyridin-2-yl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(3-fluoroethyl-6-hydroxy-pyridin-2-yl)-propionic acid;

[¹⁸F] labeled L,D-2-amino-3-(4-fluoroethyl-6-hydroxy-pyridin-2-yl)-propionic acid;

[¹⁸F] labelled alanine;

[¹⁸F] labelled valine;

[¹⁸F] labelled leucine;

[¹⁸F] labelled isoleucine; and

[¹⁸F] labelled methionine.

10. A pharmaceutical composition comprising the analogue of claim 1 and at least one of an excipient, carrier and diluent.

11. The pharmaceutical composition of claim 10, wherein the pharmaceutical composition is used as a tracer in at least one of Positron Emission, Tomography (PET) and functional Magnetic Resonance Imaging (MRI).

4. (canceled)

5. The analogue of claim 4, wherein the halogen is ¹⁸F.

6. The analogue of claim 4, wherein the halogen is ¹²³I.

7-8. -8. (canceled)

12-24. -24. (canceled)