Bifunctional tridentate pyrazolyl containing ligands for re and tc tricarbonyl complexes
View Patent ↗The present invention relates to a chelating agent of the general formula: (I), wherein m is 0 or 1; X is NR 4 or S; Y is SR 5 , NHR 5 or P(R 5 ) 2 ; R 1 and R 3 are the same or different and are selected from H, alkyl or aryl; R 2 is H, COOH, NHR 6 or (CH 2 ) n COOR 6 ; R 4 is H, alkyl, aryl, (CH 2 ) n COOR 6 or (CH2) n OR 6 ; R 5 is H, alkyl, aryl, (CH 2 ) n COOR 6 or (CH 2 ) n OR 6 , R 6 is H, alkyl or aryl; n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and when R 1 ═R 3 ═CH 3 , R 2 , R 4 and R 5 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.
1. Chelating agent of the general formula:
wherein m is 0 or 1;
X is NR 4 or S;
Y is SR 5 , NHR 6 or P(R 5 ) 2 ;
R 1 and R 3 are the same or different and are selected from H, alkyl or aryl;
R 2 is H, COOH, NHR 6 or (CH 2 ) n COOR 6 ;
R 4 is H, alkyl, aryl, (CH 2 ) n COOR 6 or (CH 2 ) n OR 6 ;
R 5 is H, alkyl, aryl, (CH 2 ) n COOR 6 or (CH 2 ) n OR 6 ;
R 6 is H, alkyl or aryl;
n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and
wherein at least one of R 1 , R 3 , R 4 , R 5 , and R 6 is phenyl or benzyl.
2. Chelating agent of the general formula:
wherein m is 0 or 1;
X is NR 4 or S;
Y is SR 5 , NHR 4 or P(R 5 ) 2 ;
R 1 , and R 3 are the same or different and are selected from H, alkyl or aryl, wherein at least one of R 1 and R 3 is aryl;
R 2 is H, COOH, NHR 6 or (CH 2 ) n COOR 6 ;
R 4 is H, alkyl, aryl, (CH 2 ) n COOR 6 or (CH 2 ) n OR 6 ;
R 5 is H, alkyl, aryl, (CH 2 ) n COOR 6 or (CH 2 ) n OR 6 ;
R 6 is H, a biomolecule, alkyl or aryl; and
n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.
3. A metal complex comprising the chelating agent of claim 1 .
4. Chelating agent as claimed in claim 2 , wherein R 6 is a biomolecule.
5. Chelating agent as claimed in claim 4 , wherein the biomolecule is selected from amino acids, peptides, proteins, oligonucleotides, polynucleotides, and sugars.
6. Chelating agent as claimed in claim 4 , wherein the biomolecule is selected from the group consisting of antibodies and ligands of tumor receptors.
7. Chelating agent as claimed in claim 4 , wherein the biomolecule is selected from the group consisting of CCK, thioglucose, glucosamine, somatostatin, neurotensin, bombesin, annexin, interleukins, growth factors, steroid hormones and molecules binding to GPIIb/IIIIa receptors.
8. Chelating agent as claimed in claim 4 , wherein the biomolecule is selected from the group consisting of glucose, thioglucose, and neurotransmitters.
9. Chelating agent as claimed in claim 4 , wherein the biomolecule is an inhibitor of the tyrosine kinase activity.
10. The chelating agent as claimed in claim 1 , wherein when R 1 ═R 3 ═CH 3 , R 2 , R 4 and R 5 are not all three H.
11. The chelating agent as claimed in claim 2 , wherein when R 1 or R 3 is CH 3 , R 2 , R 4 and R 5 are not all three H.
12. Chelating agent as claimed in claim 1 , wherein alkyl is a C 1 alkyl, C 2 alkyl, C 3 alkyl, C 4 alkyl, C 5 alkyl or C 6 alkyl.
13. Chelating agent as claimed in claim 12 , wherein 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-methyl pentyl, 2,3-dimethylbutyl.
14. Chelating agent as claimed in claim 1 , wherein n is 2, 3, 4, 5 or 6.
15. Chelating agent as claimed in claim 2 , wherein alkyl is a C 1 alkyl, C 2 alkyl, C 3 alkyl, C 4 alkyl, C 5 alkyl or C 6 alkyl.
16. Chelating agent as claimed in claim 15 , wherein 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-dimethyl butyl), 3-methylpentyl, 2,3-dimethylbutyl.
17. Chelating agent as claimed in claim 2 , wherein n is 2, 3, 4, 5 or 6.