Trimeric, macrocyclically substituted halo-benzene derivatives

1. A metal complex of formula (I)

in which

Hal stands for bromine or iodine,

A 1 stands for the radical —CONR 1 —(CH 2 ) n —NR 2 —(CO—CHZ 1 —NH) m —CO—CHZ 2 —K,

A 2 stands for the radical —NR 1 —CO—CHZ 2 —K,

R 1 and R 2 are, independently of one another, a hydrogen atom, a C 1 -C 2 -alkyl group or a monohydroxy-C 1 -C 2 -alkyl group,

Z 1 and Z 2 are, independently of one another, a hydrogen atom or a methyl group,

n is the number 2-4,

m is the number 0 or 1, and

K stands for

wherein X is a hydrogen atom or a metal ion equivalent of atomic numbers 20-29, 39, 42, 44 or 57-83, provided that at least two X stand for metal ion equivalents and optionally present free carboxy groups optionally are present as salts of organic and/or inorganic bases or amino acids or amino acid amides.

2. A metal complex according to claim 1 , wherein A 1 stands for

—CONH(CH 2 ) 2;3 NHCOCH 2 NHCOCH(CH 3 )—K,

—CONH(CH 2 ) 2;3 NHCOCH 2 NHCOCH 2 —K,

—CONH(CH 2 ) 2;3 NHCOCH 2 —K,

—CONH(CH 2 ) 2;3 NHCOCH(CH 3 )—K, or

—CON(CH 2 CH 2 OH(CH 2 ) 2 NHCOCH 2 —K.

3. A metal complex according to claim 1 ,

wherein A 2 stands for

—NHCOCH(CH 3 )—K,

—NHCOCH 2 —K,

—N(CH 3 )COCH 2 —K,

—N(CH 3 )COCH(CH) 3 —K,

—N(CH 2 CH 2 OH)COCH 2 —K, or

—N(CH 2 CH 2 OH)COCH(CH 3 )—K.

4. A metal complex according to claim 1 ,

wherein X stands for a metal ion equivalent of atomic numbers 21-29, 42, 44, or 58-70.

5. A metal complex according to claim 1 , wherein X stands for a metal ion equivalent of ions gadolinium(III), dysprosium(III), europium(III), iron(III) or manganese(II).

6. A pharmaceutical composition comprising at least one metal complex according to claim 1 , and a galenically acceptabe carrier.

7. A method for x-ray diagnosis, comprising administering to a subject an effective amount of a metal complex according to claim 1 and x-ray imaging said subject.

8. A method for MRT diagnosis, comprising administering to a subject an effective amount of a metal complex according to claim 1 and MRT imaging said subject.

9. A pharmaceutical composition according to claim 6 , which contains a metal complex according to claim 1 in a molar ratio of 2000:1 to 1:1.

10. Pharmaceutical agents according to claim 6 , wherein the metal complex is dissolved or suspended in water or is in a physiologically salt solution at a concentration of 0.001 to 1 mol/l.

11. A method for x-ray or MR diagnosis of cerebral infarction, a tumor of the liver, a space-occupying process in the liver, a tumor of the abdomen, a tumor of the kidney, or the muscle-skeleton system, or and for the visualization of a blood vessel after intraarterial injection or intravenous injection, comprising administering to a subject an effective amount of a metal complex according to claim 1 and x-ray or MR imaging said subject.

12. A process for preparing a metal complex according to claim 1 , comprising reacting a triiodoaromatic compound or a tribromoaromatic compound of formula II

with a compound of formula III

in which

Hal stands for bromine or iodine,

W stands for a protective group or a —CH 2 COOX′ group,

X′ has the meaning of X in the compound of formula (I) or is protective group,

A 1′ is —CO—NR 1 —(CH 2 ) n —NR 2 —(CO—CHZ 1 —NH) m —CO—CHZ 2 —Hal′,

A 2′ is —NR 1 —CO—CHZ 2 —Hal′,

Hal′ is chlorine or bromine,

and R 1 , R 2 , Z 1 , Z 2 , m and n are as defined in the compound of formula (I),

and then optionally removing protective group W and introducing the radical CH 2 COOX, or removing the protective group that optionally stands for X′ and then reacting with a metal oxide or metal salt of an element of one of the atomic numbers 20-29, 39, 42, 44 and 57-83.

13. A process for preparing a pharmaceutical composition according to claim 6 , wherein the at least one metal complex is dissolved or suspended in water or in a physiologically acceptable salt solution.

14. A pharmaceutical composition according to claim 6 , which is suitable for enteral or parenteral administration.

15. A pharmaceutical composition according to claim 6 , which contains a metal complex according to claim 1 in a molar ratio of 49:1 to 4:1.

16. A metal complex according to claim 1 , wherein Hal is iodine, R 1 and R 2 are hydrogen or methyl, m is 0 and n is 2.

17. A method for x-ray diagnosis, comprising administering to a subject an effective amount of a metal complex according to claim 16 and x-ray imaging said subject.

18. A method for MRT diagnosis, comprising administering to a subject an effective amount of a metal complex according to claim 16 and MRT imaging said subject.

19. A method for x-ray or MR diagnosis of cerebral infarction, a tumor of the liver, a space-occupying process in the liver, a tumor of the abdomen, a tumor of the kidney, or the muscle-skeleton system, or and for the visualization of a blood vessel after intraarterial injection or intravenous injection, comprising administering to a subject an effective amount of a metal complex according to claim 16 and x-ray or MR imaging said subject.

20. A metal complex according to claim 16 , wherein

A 1 stands for

—CONH(CH 2 ) 2;3 NHCOCH 2 NHCOCH(CH 3 )—K,

—CONH(CH 2 ) 2;3 NHCOCH 2 NHCOCH 2 —K,

—CONH(CH 2 ) 2;3 NHCOCH 2 —K,

—CONH(CH 2 ) 2;3 NHCOCH(CH 3 )—K, or

—CON(CH 2 CH 2 OH(CH 2 ) 2 NHCOCH 2 —K,

and

A 2 stands for

—NHCOCH(CH 3 )—K,

—NHCOCH 2 —K,

—N(CH 3 )COCH 2 —K,

—N(CH 3 )COCH(CH) 3 —K,

—N(CH 2 CH 2 OH)COCH 2 —K, or

—N(CH 2 CH 2 OH)COCH(CH 3 )—K.