Dimeric contrast agents

A method of MR imaging comprising:

• administering a chelated complex of a compound of formula (I)
• where:
• R is —CH(R1)—COOH, where:
• R1 is H or a C1-C3 alkyl chain that is optionally substituted by a C1-C3 alkoxy or C1-C3 hydroxyalkoxy group;
• n is 1 or 2;
• R2 is selected from the group consisting of:
• an aryl ring;
• a cycloalkyl ring;
• a C1-C5 alkyl substituted by one ore more C1-C8 hydroxyalkoxy groups, or by a cycloalkyl ring;
• a group of formula —(CH2)sCH(R3)-G;
• and a C5-C12 hydroxyalkyl comprising at least 2 hydroxyl groups;
• in which
• s is 0, 1 or 2;
• R3 is H, or an arylalkylene or cycloalkyl-alkylene having from 1 up to 3 carbon atoms in the alkylene chain;
• G is a group selected from —PO(OR4)2, —PO(R5)(OR4) and —COOH;
• in which
• R4 independently of one another is H or C1-C5 alkyl;
• R5 is an aryl or cycloalkyl ring, or C1-C5 alkyl which is optionally substituted by an aryl or cycloalkyl ring;
• and
• L is a C1-C6 alkylene interrupted by one or more —N(R′2)— groups, and optionally substituted by one or more substituent groups selected from hydroxyl, C1-C3 alkoxy and C1-C3 hydroxyalkoxy, where
• R′2 is, independently, as defined for R2
• with two paramagnetic metal ions selected from the group consisting of Fe2+, Fe3+, Cu2+, Cr3+, Gd3+, Eu3+, Dy3+, La3+, Yb3+ and Mn2+, or a physiologically acceptable salt thereof, to a patient;
• submitting the patient to a radiation frequency selected to excite non-zero proton spin nuclei of the chelated complex;
• and
• recording a MR signal from said nuclei.

A compound of formula (I)

• where:
• R is —CH(R1)—COOH, where:
• R1 is H or a C1-C3 alkyl chain that is optionally substituted by a C1-C3 alkoxy or C1-C3 hydroxyalkoxy group;
• n is 1 or 2;
• R2 is selected from the group consisting of:
• an aryl ring;
• a cycloalkyl ring;
• a C1-C5 alkyl substituted by one ore more C1-C8 hydroxyalkoxy groups, or by a cycloalkyl ring;
• a group of formula —(CH2)sCH(R3)-G;
• and a C5-C12 hydroxyalkyl comprising at least 2 hydroxyl groups;
• in which
• s is 0, 1 or 2;
• R3 is H, or an arylalkylene or cycloalkyl-alkylene having from 1 up to 3 carbon atoms in the alkylene chain;
• G is a group selected from —PO(OR4)2, —PO(R5)(OR4) and —COOH;
• in which
• R4 independently of one another is H or C1-C5 alkyl;
• R5 is an aryl or cycloalkyl ring, or C1-C5 alkyl which is optionally substituted by an aryl or cycloalkyl ring;
• and
• L is a C1-C6 alkylene interrupted by one or more —N(R′2)— groups, and optionally substituted by one or more substituent groups selected from hydroxyl, C1-C3 alkoxy and C1-C3 hydroxyalkoxy, where
• R′2 is, independently, as defined for R2, or a physiologically acceptable salt thereof.