Methods to treat conditions mediated by chemokine receptors

1. A method for ameliorating a disorder modulated by the CXCR4 chemokine receptor in a subject which method comprises administering to a subject in need of such treatment an effective amount of a compound of formula (I),

V—CR 1 R 2 —Ar—CR 3 R 4 —N(R 5 )—(CR 6 R 7 ) x —R 8   (I)

wherein V is a 1,4,8,11-tetraazacyclotetradecanyl group, and which may optionally comprise a fused aromatic or heteroaromatic ring;

R 1 to R 7 are independently hydrogen, or straight, branched or cyclic C 1-6 alkyl;

R 8 is a heterocyclic group, a substituted aromatic group, or a mercaptan group;

Ar is an aromatic ring or heteroaromatic ring each said ring being optionally substituted;

x is 1 or 2;

or the acid addition salts and metal complexes thereof, or a pharmaceutically acceptable composition thereof;

wherein said disorder comprises a deficiency in vascularization of the gastrointestinal tract, hematopoiesis, or cerebellar development; abnormal basal leukocyte trafficking; abnormal extravasation and tissue infiltration of leukocytes in response to inciting antigens; or abnormal calcium ion transport.

2. The method of claim 1 , wherein said disorder comprises a deficiency in vascularization of the gastrointestinal tract.

3. The method of claim 1 , wherein said disorder comprises a deficiency in hematopoiesis.

4. The method of claim 1 , wherein said disorder comprises a deficiency in cerebellar development.

5. The method of claim 1 , wherein said disorder comprises abnormal basal leukocyte trafficking.

6. The method of claim 1 , wherein said disorder comprises abnormal extravasation and tissue infiltration of leukocytes in response to inciting antigens.

7. The method of claim 1 , wherein said disorder comprises abnormal calcium ion transport.

8. The method of claim 1 , wherein any substituents on Ar are selected from the group consisting of alkyl, aryl, amino, alkoxy, hydroxy, halogen, carboxyl and carboxamido.

9. The method of claim 1 , wherein R 8 is selected from the group consisting of pyridine, pyrimidine, pyrazine, imidazole, thiophene, thiophenyl, aminobenzyl, piperidinyl, piperazinyl and a mercaptan group.

10. The method of claim 1 , wherein each of R 1 –R 7 is hydrogen.

11. The method of claim 1 , wherein the compound of formula (I) is selected from the group consisting of:

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-2-(amino-methyl)pyridine (AMD 3465);

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-N-methyl-2-(aminomethyl)pyridine (AMD 3538);

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-4-(amino-methyl)pyridine (AMD 3500);

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-3-(amino-methyl)pyridine (AMD 3499);

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-(2-amino-methyl-5-methyl)pyrazine (AMD 3498);

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-2-(amino-ethyl)pyridine (AMD 3497);

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-2-(amino-methyl) thiophene (AMD 3516);

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-2-(amino-ethyl)mercaptan (AMD 3530);

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-2-amino-benzylamine (AMD 3517);

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-4-amino-benzylamine (AMD 3544);

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-4-(amino-ethyl)imidazole (AMD 3543); or

N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-benzylamine (AMD 3529) or

the acid addition salts and metal complexes thereof.

12. The method of claim 11 , wherein said compound of formula (I) is N-[1,4,8,11-Tetraazacyclotetradecanyl-1,4-phenylenebis(methylene)]-2-(amino-methyl)pyridine AMD 3465).