Contrast agents for magnetic resonance imaging

A contrast agent for magnetic resonance imaging comprising a chelating ligand and a transition metal ion, said ligand carrying a substituent capable of reacting chemically or biochemically with a target substance while bringing about a change in the spin state, and comprising:

• a) either the formula (I)
• in which:
• R4 represents a hydrogen atom or a linear of branched alkyl group of 1 to 4 carbon atoms or an aryl radical;
• W represents a —(CH2)m— group, m being equal to 0 or to 1;
• R5 represents a hydrogen atom, or represents a -E-R6 or —C6X4—Y—R6 group, in which E and C6X4—Y are spacer groups and R6 represents a β-galactosyl group, a β-glucoronyl group, a L-leucyl group, a —COC5H11 group, a group of α,β-dihydroxyacetone type, a prolyl group or a phosphoryl group, X is an electron-withdrawing group, at least one X of C6X4—Y being selected from the group consisting of methyl, chloro, fluoro, nitro, methoxy, carboxy and acetamido groups;
• E is an —O—CO—(CR′2)n—Y— group in which the R′ groups represent, independently of one another, a hydrogen atom or a methyl group or two R′ groups carried by two neighboring carbon atoms together form a 5- or 6-membered aliphatic or aromatic ring carried by the two neighboring carbon atoms;
• n is an integer equal to 3 or 4;
• Y is a heteroatom chosen from an oxygen atom, a nitrogen atom or a sulphur atom, it being understood that:
• i) when R5 represents a -E-R6 or —C6X4—Y—R6 group (complexes Ia), the substituents R1 to R3, denoted by Ri, represent, independently of one another, a hydrogen atom or a group chosen in order to adjust the properties of solubility and of dispersibility in biological media and of magnetic moment of the complex, it also being possible for one of the Ri groups to represent a group capable of undergoing electronic modification of the neighboring pyridyl group by reaction with the target substance;
• ii) when R5 represents a hydrogen atom (complexes Ib), one of the Ri groups represents a group —CH(OH)CH(COOH)NH2, it being possible for the remaining Ri groups to represent, independently of one another, a hydrogen atom, a halogen atom or a group chosen from the —COOR7 groups in which R7 is an alkyl group having from 1 to 4 carbon atoms, a —NO2 group or a —CHO group;
• b) or the formula (II)
• in which:
• R1 and R2, denoted by Ri, represent, independently of one another, a hydrogen atom or a group chosen in order to adjust the properties of solubility and of dispersibility in biological media and of magnetic moment of the complex;
• R4 and W are as defined above;
• R5 represents a group (—C6X4—Y—R6) in which X is an electron-withdrawing group, Y is a heteroatom chosen from an oxygen atom, a nitrogen atom or a sulfur atom, and R6 represents a β-galactosyl group, a β-glucuronyl group, a L-leucyl group, a —COC5H11 group, a group of α,β-dihydroxyacetone type, a prolyl group or a phosphoryl group;
• Z is a divalent group which forms, with the two nitrogen atoms which carry it, an aromatic benzotriazole, triazole, tetrazole or pyrazole ring, it being possible for said aromatic ring to carry an NO2 substituent.