Bifunctional tridentate pyrazolyl containing ligands for re and tc tricarbonyl complexes

• US 20060198785A1
• Filed: 04/15/2004
• Published: 09/07/2006
• Est. Priority Date: 04/15/2003
• Status: Active Grant

• Current Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Original Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Inventors: Correia, Joao Domingos Galamba, Vitor, Rute, Santos, Isabel Rego, Alves, Susana, Paulo, Antonio Manuel Rocha
• Granted Patent: US 7,682,601 B2
• Time in Patent Office: Days
• US Class Current: 424/1.69
• CPC Class Codes: A61K 51/0476 complexes from monodendate ligands, e.g. sestamibi
• CPC Class Codes: A61K 51/0478 complexes from non-cyclic ligands, e.g. EDTA, MAG3
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07H 21/02 with ribosyl as saccharide radical

Abstract

The present invention relates to a chelating agent of the general formula: (I), wherein m is 0 or 1; X is NR₄ or S; Y is SR₅, NHR₅ or P(R₅)₂; R₁ and R₃ are the same or different and are selected from H, alkyl or aryl; R₂ is H, COOH, NHR₆ or (CH₂)_nCOOR₆; R₄ is H, alkyl, aryl, (CH₂)_nCOOR₆ or (CH2)_nOR₆; R₅ is H, alkyl, aryl, (CH₂)_nCOOR₆ or (CH₂)_nOR₆, R₆ is H, alkyl or aryl; n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and when R₁═R₃═CH₃, R₂, R₄ and R₅ are not all three H. The invention further relates to a method and kit for the preparation of radiolabeled biomolecules while using the chelating agent.

Claims

1. Chelating agent of the general formula:

2. Chelating agent as claimed in claim 1, wherein the alkyl is a C₁ alkyl, C₂ alkyl, C₃ alkyl, C₄ alkyl, C₅ alkyl or C₆ alkyl.

3. Chelating agent as claimed in claim 2, wherein the alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl (2-methylpentyl), neohexyl (2,2-dimethylbutyl), 3-methylpentyl, 2,3-dimethylbutyl.

4. Chelating agent as claimed in claim 1, wherein the aryl is monocyclic or polycyclic, C₁₀-C₁₈, and optionally substituted with one or more groups selected from alkyl, carboxy, oxo, amino, alkoxy and aldehyde.

5. Chelating agent as claimed in claim 4, wherein the aryl is phenyl or benzyl.

6. Chelating agent as claimed in claim 1, wherein n is 2, 3, 4, 5 or 6.

7. Chelating agent as claimed in claim 1, which agent is a pyrazolyl-polyamine of the general formula:

8. Chelating agent as claimed in claim 1, which agent is a pyrazolyl-aminothioether of the general formula:

9. Chelating agent as claimed in claim 1, which agent is a pyrazolyl-polythioether of the general formula:

10. Chelating agent as claimed in claim 1, which agent is a pyrazolyl-aminophosphine of the general formula:

11. Chelating agent as claimed in claim 1, which agent is a pyrazolyl-thioetherphosphine of the general formula:

12. Chelating agent as claimed in claim 1, wherein X and Y are N, R₆ is H, C₁ alkyl, C₂ alkyl, C₃ alkyl, C₄ alkyl, C₅ alkyl or C₆ alkyl, phenyl, benzyl or a biomolecule.

13. Chelating agent as claimed in claim 1, wherein X and Y are S, R₆ is H, C₁ alkyl, C₂ alkyl, C₃ alkyl, C₄ alkyl, C₅ alkyl or C₆ alkyl, phenyl, benzyl or a biomolecule.

14. Chelating agent as claimed in claim 1, wherein X is N, Y is S, R₆ is H, C₁ alkyl, C₂ alkyl, C₃ alkyl, C₄ alkyl, C₅ alkyl or C₆ alkyl, phenyl, benzyl or a biomolecule.

15. Chelating agent as claimed in claim 1, wherein X is S, Y is N, R₆ is H, C₁ alkyl, C₂ alkyl, C₃ alkyl, C₄ alkyl, C₅ alkyl or C₆ alkyl, phenyl, benzyl or a biomolecule.

16. Chelating agent as claimed in claim 1, wherein X is S, Y is P(R₅)₂, R₆ is H, C₁ alkyl, C₂ alkyl, C₃ alkyl, C₄ alkyl, C₅ alkyl or C₆ alkyl, phenyl, benzyl or a biomolecule.

17. Chelating agent as claimed in claim 1, wherein X is N, Y is P(R₅)₂, R₆ is H, C₁ alkyl, C₂ alkyl, C₃ alkyl, C₄ alkyl, C₅ alkyl or C₆ alkyl, phenyl, benzyl or a biomolecule.

18. Chelating agent as claimed in claim 1, wherein R₆ is a biomolecule.

19. Chelating agent as claimed in claim 18, wherein the biomolecule is selected from amino acids, peptides, proteins, oligonucleotides, polynucleotides, and sugars.

20. Chelating agent as claimed in claim 19, wherein the biomolecule is selected from the group consisting of antibodies and ligands of tumor receptors.

21. Chelating agent as claimed in claim 19, wherein the biomolecule is selected from the group consisting of CCK, thioglucose, glucosamine, somatostatin, neurotensin, bombesin, CCK, annexin, interleukins, growth factors, steroid hormones and molecules binding to GPIIb/IIIa receptors.

22. Chelating agent as claimed in claim 19, wherein the biomolecule is selected from the group consisting of glucose, thioglucose, and neurotransmitters.

23. Chelating agent as claimed in claim 19, wherein the biomolecule is an inhibitor of the tyrosine kinase activity.

24. Chelating agent as claimed in claim 1, which agent is a compound of the following formula:

25. Chelating agent as claimed in claim 1, which agent is a compound of the following formula:

26. Chelating agent as claimed in claim 1, which agent is a compound of the following formula:

27-35. -35. (canceled)

36. Chelating agent of the general formula:

37. Chelating agent of the general formula:

38. Chelating agent of the general formula:

39. Chelating agent of the general formula:

40. Chelating agent of the general formula: