Claims
- 1. Perfluoroalkyl-containing metal complexes with sugar radicals of formula I in whichR is a monosaccharide or oligosaccharide radical that is bonded via the 1-OH position or 1-SH position, Rf is a perfluorinated, straight-chain or branched carbon chain with the formula —CnF2nE, in which E is a terminal fluorine, chlorine, bromine, iodine or hydrogen atom, and n is a number from 4-30, K is a metal complex of formula II in whichR1 is a hydrogen atom or a metal ion equivalent of atomic numbers 21-29, 31-33, 37-39, 42-44, 49 or 57-83, provided that at least two R1 are metal ion equivalents, R2 and R3, independently of one another, are hydrogen, C1-C7 alkyl, benzyl, phenyl, —CH2OH or —CH2OCH3, and U is —C6H4—O—CH2-ω-, —(CH2)1-5-ω, a phenylene group, —CH2—NHCO—CH2—CH(CH2COOH)—C6H4-ω-, —C6H4—(OCH2CH2)0-1—N(CH2COOH)—CH2-ω or a C1-C12 alkylene group or a C7-C12-C6H4—O group that is optionally interrupted by one or more oxygen atoms, 1 to 3 —NHCO groups or 1- to 3 —CONH groups and/or is substituted with 1 to 3 —(CH2)0-5COOH groups, whereby ω stands for the binding site to —CO—, or of formula III in which R1 has the above-mentioned meaning, R4 is hydrogen or a metal ion equivalent that is mentioned under R1, and U1 is —C6H4—O—CH2-ω-, whereby ω means the binding site to —CO—or of formula IV in which R1 and R2 have the above-mentioned meaning or of formula V A or V B in which R1 has the above-mentioned meaning, or of formula VI in which R1 has the above-mentioned meaning, or of formula VII in which R1 has the above-mentioned meaning, and U1 is —C6H4—O—CH2-ω-, whereby ω means the binding site to —CO—, or of formula VIII in which R1 the above-mentioned meaning, and in radical K, optionally present free acid groups optionally can be present as salts of organic and/or inorganic bases or amino acids or amino acid amides, G for the case that K means metal complexes II to VII, is a radical that is functionalized in at least three places and that is selected from radicals a) to j) below andG for the case that K means metal complex VIII, is a radical that is functionalized in at least three places and that is selected from k) or l), whereby α is the binding site of G to complex K, β is the binding site of G to radical Y and γ is the binding site of G to radical Z, Y is —CH2, δ-(CH2)nCO-β (whereby n=1-5), δ-CH2—CHOH—CO-β or δ-CH(CHOH—CH2OH)—CHOH—CHOH—CO-β, whereby δ is the binding site to sugar radical R and β is the binding site to radical G, Z stands for γ-COCH2—N(C2H5)—SO2-ξ, γ-COCH2—O—(CH2)2—SO2-ξ, or γ-NHCH2CH2—O—CH2CH2-ξ, whereby γ is the binding site of Z to radical G, and ξ is the binding site of Z to perfluorinated radical Rf, and 1 and m, independently of one another, are the whole numbers 1 or 2, and p is a whole number 1 to 4.
- 2. A metal complex according to claim 1, wherein metal ion equivalent R1 is an element of atomic numbers 21-29, 39, 42, 44 or 57-83.
- 3. A metal complex according to claim 1, wherein metal ion equivalent R1 is an element of atomic numbers 27, 29, 31-33, 37-39, 43, 49, 62, 64, 70, 75 or 77.
- 4. A metal complex according to claim 1, wherein R is a monosaccharide radical with 5 to 6 C atoms or its deoxy compound.
- 5. A metal complex according to claim 1, wherein K is a metal complex of formula II.
- 6. A metal complex according to claim 5, wherein R2 and R3, independently of one another, are hydrogen or C1-C4 alkyl.
- 7. A metal complex according to claim 1, wherein E in formula —CnF2nE is a fluorine atom.
- 8. A metal complex according to claim 1, wherein G in formula I is a lysine radical (a) or (b).
- 9. A metal complex according to claim 1, wherein Z in formula I is whereby γ is the binding site of Z to radical G, and ξ is the binding site of Z to perfluorinated radical Rf.
- 10. A metal complex according to claim 1, wherein in formula I, Y is δ-(CH2)nCO-β, whereby δ is the binding site to sugar radical R and β is the binding site to radical G.
- 11. A metal complex according to claim 1, wherein U in metal complex K is —CH2— or —C6H4—O—CH2-ω, whereby ω is the binding site to —CO—.
- 12. A method for the production of contrast media for use in NMR diagnosis and x-ray diagnosis comprising formulating a metal complex according to claim 2 in a physiologically administrable form for NMR diagnosis and x-ray diagnosis.
- 13. A method for the production of contrast media for infarction and necrosis imaging comprising formulating a metal complex according to claim 12 in a physiologically administrable form for infarction and necrosis imaging.
- 14. A method for the production of contrast media for use in radiodiagnosis and radiotherapy comprising formulating a metal complex according to claim 12 in a physiologically administrable form for radiodiagnosis and radiotherapy.
- 15. A method for the production of contrast media for lymphography in the diagnosis of changes in the lymphatic system comprising formulating a metal complex according to claim 2 in a physiologically administrable form for lymphography.
- 16. A method for the production of contrast media for use in indirect lymphography comprising formulating a metal complex according to claim 2 in a physiologically administrable form for indirect lymphography.
- 17. A method for the production of contrast media for use in intravenous lymphography comprising formulating a metal complex according to claim 2 in a physiologically administrable form for intravenous lymphography.
- 18. A method for the production of contrast media for visualizing the vascular space comprising formulating a metal complex according to claim 2 in a physiologically administrable form suitable for visualizing the vascular space.
- 19. A method for the production of contrast media for tumor imaging comprising formulating a metal complex according to claim 2 in a physiologically administrable form suitable for tumor imaging.
- 20. A method for the production of contrast media for the study of abnormal capillary permeability comprising formulating a metal complex according to claim 2 in a physiologically administrable form suitable for the study of abnormal capillary permeability.
- 21. Pharmaceutical composition that contains at least one physiologically compatible compound according to claim 1, optionally with the additives that are commonly used in galenicals.
- 22. Process for the production of perfluoroalkyl-containing complexes with sugar radicals of formula I with K being a metal complex of one of formulas II to VII according to claim 1, G being a radical a) to j) according to claim 1, and Y, Z, R, Rf, m, p and l as defined in claim 1, which comprises reacting a carboxylic acid of formula IIa in which R5 is a metal ion equivalent of atomic numbers 21-29, 31-33, 37-39, 42-44, 49 or 57-83 or a carboxyl protective group, and R2, R3 and U have the above-mentioned meaning, or a carboxylic acid of general formula IIIa in which R4, R5, and U1 have the above-mentioned meaning or a carboxylic acid of formula IVa in which R5 and R2 have the above-mentioned meaning or a carboxylic acid of formula Va or Vb in which R5 has the above-mentioned meaning or a carboxylic acid of formula VIa in which R5 has the above-mentioned meaning or a carboxylic acid of formula VIIa in which R5 and U1 have the above-mentioned meanings, in optionally activated form with an amine of formula IX in which G, R, Rf, Y, Z, m and p have the meaning indicated in the claim, in a coupling reaction, and optionally subsequently cleaving optionally present protective groups to provide a metal complex of formula I, or if R5 has the meaning of a protective group, reacting after cleavage of these protective groups in a subsequent step with at least one metal oxide or metal salt of an element of atomic numbers 21-29, 31-33, 37-39, 42-44, 49 or 57-83, and then, optionally, optionally present, acidic hydrogen atoms are substituted by cations of inorganic and/or organic bases, amino acids or amino acid amides.
- 23. Process for the production of perfluoroalkyl-containing metal complexes with sugar radicals of formula I with K being a metal complex of formula VIII according to claim 1, G being a radical k) or l) according to claim 1, and Y, Z, R, Rf, m, p, and l having the meaning according to claim 1, comprising reacting an amine of formula VIIIa in which R5 is a metal ion equivalent of atomic numbers 21-29, 31-33, 37-39, 42-44, 49 or 57-83, or a carboxyl protective group, with an optionally activated carboxylic acid of formula X in which G, R, Rf, Y, Z, m and p have the meanings indicated in the claim, in a coupling reaction and optionally subsequently cleaving optionally present protective groups to provide a metal complex of formula I or if R5 has the meaning of a protective group, reacting after cleavage of these protective groups in a subsequent step with at least one metal oxide or metal salt of an element of atomic numbers 21-29, 31-33, 37-39, 42-44, 49 or 57-83, and then, optionally, optionally present acid hydrogen atoms are substituted by cations of inorganic and/or organic bases, amino acids or amino acid amides.
- 24. A metal complex according to claim 1, wherein R is a glucose, mannose or galactose radical.
- 25. A metal complex according to claim 1, wherein metal ion equivalent R1 is a gadolinium(III), terbium(III), dysprosium(III), holmium(III), erbium(III), iron(III) or manganese(II) ion.
- 26. A metal complex according to claim 1, wherein R2 is methyl and R3 is hydrogen.
Priority Claims (1)
Number |
Date |
Country |
Kind |
100 40 381 |
Aug 2000 |
DE |
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Parent Case Info
This application claims priority to provisional application No. 60/234,952, filed Sep. 26, 2000.
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Provisional Applications (1)
|
Number |
Date |
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|
60/234952 |
Sep 2000 |
US |