US 5,649,537 AGranted

Paramagnetic metal icon chelates and use thereof as contrast agents in magnetic resonance imaging

AssigneeDibra S.p.A.

InventorsPier Lucio Anelli, Christoph De Haen, Luciano Lattuada, Pierfrancesco Morosini, Fulvio Uggeri

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Abstract

Novel paramagnetic metal ion chelates and their use as contrast agents in the diagnostic technique known as "magnetic resonance imaging" (M.R.I.) of the gastrointestinal tract and particularly of the liver, are described. The novel compounds result from the conjugation of a bile acid with a chelating agent and are capable of chelating the ions of bivalent and trivalent metals. The compounds have formula A-L-B in which A is the residue of a bile acid and derivatives of a bile acid, B is the residue of a chelating agent of a bivalent or trivalent metal ion having an atomic number of 20 to 31, 39, 42, 43, 44, 49, 57 to 83, L is a ligand between A and B.

Claims20

Dependent claims

A compound of general formula (I)

A-L-B (I)
wherein
A is the residue of a bile acid, said residue being the group of a bile acid obtainable by bioconversion from cholesterol, said bile acid being a member selected from the group consisting of cholic, deoxycholic, chenodeoxycholic, ursodeoxycholic, and lithocholic or said residue A is the conjugation product thereof with taurine or glycine:
L is a ligand between at least one of the C-3, C-7, C-12 and C-24 positions of the residue of said bile acid and B;
and L has the formula II ##STR12## in which m is an integer varying from 1 to 10, and when m has a value above 1, Y have different meanings,
Y corresponds to the following succession of groups, ##STR13## wherein n, 1 and q are 0 or 1,
p varies between 0 and 10,
X is an 0 atom, a S atom, or a --NR group, in which
R is a H atom, or a (C.sub.1 -C.sub.5) alkyl group,
K is an unsubstituted or substituted benzene ring or a --CHR.sub.1 group,
wherein
R.sub.1 is a hydrogen atom, a --COOH group, or a --SO.sub.3 H group,
Z is an O atom, a S atom, or one of --CO-- or --CS-- groups,
B is the residue of a chelating agent of a bivalent or trivalent metal ion having an atomic number varying from 20 to 31, 39, 42, 43, 44, 49, or from 57 to 83 with the proviso that at least one of l, n, q, p is different from O and when X and Z are both O or S atoms, q or n is equal to 1,
and complex chelates of said compound of formula (I) with ions of metal elements having atomic number ranging from 20 to 31, 39, from 42 to 44, 49 and from 57 to 83 and salts thereof with a) a physiologically acceptable organic base which is a primary, secondary, or a tertiary amine or a basic amino acid, b) with an inorganic base whose cations are sodium, potassium, magnesium, calcium or mixtures thereof, or c) with a physiologically acceptable anion of an organic acid which is the acetate, the succinate, the citrate, the fumarate, the maleate, the oxalate, or with an anion of an inorganic halohydric acid.

12 more elements

The method of obtaining an image of at least one of an organ and tissue of human and animal body which consists of carrying out nuclear magnetic resonance to obtain a diagnostic formulation by administration orally or parenterally of one of the complex chelates of a compound of formula (I)

A-L-B (I),
wherein
A is the residue of a bile acid, said residue being the group of a bile acid obtainable by bioconversion from cholesterol, said bile acid being a member selected from the group consisting of cholic, deoxycholic, chenodeoxycholic, ursodeoxycholic and lithocholic, or said residue A is the conjugation product thereof with taurine or glycine;
L is a ligand between at least one of the C-3, C-7, C-12 and C-24 positions of the residue of said bile acid and B;
and L has formula (II) ##STR18## in which m is an integer varying from 1 to 10, and when m has a value above 1, Y have different meanings,
Y corresponds to the following succession of groups, ##STR19## wherein n, 1 and q are 0 or 1,
p varies between 0 and 10,
X is an O atom, a S atom, or a --NR group, in which
R is a H atom, or a (C.sub.1 -C.sub.5) alkyl group,
K is an unsubstituted or substituted benzene ring or a --CHR.sub.1 group,
wherein
R.sub.1 is a hydrogen atom, a --COOH group, or a --SO.sub.3 H group,
Z is an O atom, a S atom, or one of --CO-- or --CS-- groups,
B is the residue of a chelating agent of a bivalent or trivalent metal ion having an atomic number varying from 20 to 31, 39, 42, 43, 44, 49, or from 57 to 83
with the proviso that at least one of l, n, q, p is different from O and when X and Z are both O or S atoms, q or n is equal to 1, and complex chelates of said compound of formula (I) with ions of metal elements having atomic number ranging from 20 to 31, 39, from 42 to 44, 49 and from 57 to 83 and salts thereof with a) a physiologically acceptable organic base which is a primary, secondary, or a tertiary amine or a basic amino acid, b) with an inorganic base whose cations are sodium, potassium, magnesium, calcium or mixtures thereof, or c) with a physiologically acceptable anion of an organic acid which is the acetate, the succinate, the citrate, the fumarate, the maleate, the oxalate, or with an anion of the inorganic halohydric acid.

12 more elements

Dependencies are inferred from the claim text.