Methods and compounds for enhancing contrast in magnetic resonance imaging (MRI)

A method of enhancing contrast in a magnetic resonance image of a subject, the method comprising:

• (a) administering to the subject, a compound of Formula I(b) or a hydrate thereof:
• wherein
• R1 and R5 are each independently C1-6alkyl or aryl;
• R2 and R4 are each independently H, —OH, halo, C1-6alkyl, aryl or C1-3alkyleneC(O)OR6, wherein R6 is H or C1-6alkyl;
• n is 1 or 2;
• when n is 1, R3 is H, —OH, halo, C1-6alkyl, aryl or C1-3alkyleneC(O)OR6, wherein R6 is H or C1-6alkyl;
• when n is 2, R3 represents a single bond;
• X is a pharmaceutically acceptable counteranion;
• Z is —(CR7R8CR9R10-A)p-(CR11R12CR13R14)—;
• wherein
• A is O;
• p is 2, 3 or 4;
• represents a single or double bond;
• when is a double bond, one of R7/R8 and R9/R10 or R11/R12 and R13/R14, as applicable, is not present;
• and
• R7 to R14 are each independently H, C1-6alkyl or aryl;
• or
• one of R7/R8 and R9/R10 and/or R11/R12 and R13/R14, together with the carbon atoms to which they are attached, form a 5-6 membered carbocycle;
• the N and A atoms in the compound of Formula I(b) form an N3Ap donor set for coordinating with M;
• M is selected from Fe3+, Fe2+, Co2+, Zn2+, Mn3+, Mn2+ and Gd3+ and is coordinated in an equatorial fashion by at least three atoms of the N3Ap donor set;
• when M is Fe2+, Co2+, Zn2+ or Mn2+, m is 2;
• and
• when M is Fe3+, Mn3+ or Gd3+, m is 3;
• and
• (b) obtaining a magnetic resonance image of the subject.