Ligands for improving metal chelate formation kinetics
AssigneeMallinckrodt Medical, Inc.
InventorAnanthachari Srinivasan
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Abstract
Amide-thiolate ligands having improved metal chelate formation kinetics are disclosed. The ligands include a tertiary amine strategically located to facilitate rapid formation of an amine-amide-thiolate intermediate complex, followed by transfer of the metal to a thermodynamically stable amide-thiolate complex. The amide-thiolate ligands of the present invention may be used for post formed labeling of biological substances for use in the fields of diagnosis and therapy.
Claims8
A N.sub.3 S ligand having the general structure:
- ##STR14## where at least A.sub.1, A.sub.2, or A.sub.3 is --(CH.sub.2).sub.n NR.sub.1 R.sub.2, and at least one of the remaining A.sub.1, A.sub.2, or A.sub.3 is --(CH.sub.2).sub.n' -- X, and the remaining A.sub.1, A.sub.2, or A.sub.3 is H or an alkyl;
- Y is H or --(CH.sub.2).sub.n" --COOH;
- X is a functional group for use in coupling the ligand to a biomolecule;
- R.sub.1 and R.sub.2 may be the same or different and are lower alkyl, R.sub.1 or R.sub.2 may optionally contain a functional group X, such that if R.sub.1 or R.sub.2 contains X, then the remaining A.sub.1, A.sub.2, or A.sub.3 are H or an alkyl;
- n is from 2-5, n' is from 1-10, and n" is from 0-4;
- and PG is a sulfur protecting group.
A N.sub.2 S.sub.2 ligand having the general structure:
- ##STR15## Where X is a functional group for use in coupling the ligand to a biomolecule;
- n is from 2-5;
- R.sub.1 and R.sub.2 may be the same or different lower alkyl group;
- and PG.sub.1 and PG.sub.2 may be the same or different and are sulfur protecting groups, at least PG.sub.1 or PG.sub.2 is acid labile.
A diagnostic composition suitable for administration to a warm-blooded animal comprising:
- a diagnostically effective quantity of a N.sub.3 S ligand having the general structure:
- ##STR16## where at least A.sub.1, A.sub.2, or A.sub.3 is --(CH.sub.2).sub.n NR.sub.1 R.sub.2, and at least one of the remaining A.sub.1, A.sub.2, or A.sub.3 is --(CH.sub.2).sub.n' --X, and the remaining A.sub.1, A.sub.2, or A.sub.3 is H or an alkyl;
- Y is H or --(CH.sub.2).sub.n" --COOH;
- X is a functional group for use in coupling the ligand to a biomolecule;
- R.sub.1 and R.sub.2 may be the same or different and are lower alkyl, R.sub.1 or R.sub.2 may optionally contain a functional group X, such that if R.sub.1 or R.sub.2 contains X, then the remaining A.sub.1, A.sub.2, or A.sub.3 are H or an alkyl;
- n is from 2-5, n' is from 1-10, and n" is from 0-4;
- and PG is a sulfur protecting group, wherein the ligand in coupled to a biomolecule and wherein the ligand is complexed with a radionuclide selected from the group consisting of .sup.99m Tc, .sup.111 In, and .sup.62 Cu;
- and
- a pharmaceutically acceptable carrier.
A therapeutic composition suitable for administration to a warm-blooded animal comprising:
- a therapeutically effective quantity of a N.sub.3 S ligand having the general structure:
- ##STR17## where at least A.sub.1, A.sub.2, or A.sub.3 is --CH.sub.2).sub.n NR.sub.1 R.sub.2 --, and at least one of the remaining A.sub.1, A.sub.2, or A.sub.3 is --(CH.sub.2).sub.n' --X, and the remaining A.sub.1, A.sub.2, or A.sub.3 is H or an alkyl;
- Y is H or --(CH.sub.2).sub.n" --COOH;
- X is a functional group for use in coupling the ligand to a biomolecule;
- R.sub.1 and R.sub.2 may be the same or different and are lower alkyl, R.sub.1 or R.sub.2 may optionally contain a functional group X, such that if R.sub.1 or R.sub.2 contains X, then the remaining A.sub.1, A.sub.2, or A.sub.3 are H or an alkyl;
- n is from 2-5, n' is from 1-10, and n" is from 0-4;
- and PG is a sulfur protecting group, wherein the ligand in coupled to a biomolecule and wherein the ligand is complexed with a radionuclide selected from the group consisting of .sup.186 Re, .sup.188 Re, .sup.67 Cu, .sup.90 Y, and .sup.60 Co;
- and
- a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.