Bifunctional polyazamacrocyclic chelating agents

1. A bifunctional polyazamacrocyclic chelating agent of the formula (I):

wherein:

each Q is independently (CHR 5 ) p CO 2 R or (CHR 5 ) p PO 3 R 6 R 7 ;

Q 1 is hydrogen, (CHR 5 ) w CO 2 R or (CHR 5 ) w PO 3 R 6 R 7 ;

each R is independently hydrogen, benzyl or C 1 -C 4 alkyl;

R 6 and R 7 are independently H, C 1 -C 6 alkyl or (C 1 -C 2 alkyl)phenyl;

each R 5 is independently hydrogen; C 1 -C 4 alkyl or (C 1 -C 2 alkyl) phenyl;

A is CH, N, C—Br, C—Cl, C—SO 3 H, C—OR 8 , C—OR 9 , N + —R 10 X − , or

Z and Z 1 independently are CH, N, C—SO 3 H, N + —R 10 X − , C—CH 2 —OR 8 or C—C(O)—R 11 ;

E is O, S or P;

R 8 is H, C 1 -C 5 alkyl, benzyl, or benzyl substituted with at least one R 12 ;

R 9 is C 1 -C 16 alkylamino;

R 10 is C 1 -C 16 alkyl, benzyl, or benzyl substituted with at least one R 12 ;

R 11 is —O—(C 1 -C 3 alkyl), OH or NHR—;

R 12 is H, NO 2 , NH 2 , isothiocyanato, semicarbazido, thiosemicarbazido, malcimido, bromoacetamido or carboxyl;

X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond;

n is 0 or 1;

m is an integer from 0 to 10 inclusive;

p is 1 or 2;

r is 0 or 1;

w is 0 or 1;

L is a linker/spacer group covalently bonded to, and replaces one hydrogen atom of one of the carbon atoms to which it is joined, said linker/spacer group being represented by the formula:

wherein:

s is an integer of 1;

t is an integer of 0 to 20 inclusive;

R 1 is an electrophilic or nucleophilic moiety which allows for covalent attachment to a biological carrier, or synthetic linker which can be attached to a biological carrier, or precursor thereof; and

Cyc represents a cyclic aliphatic moiety, aromatic moiety, aliphatic heterocyclic moiety, or aromatic heterocyclic moiety, each of said moieties optionally substituted with one or more groups which do not interfere with binding to a biological carrier;

or a pharmaceutically acceptable salt thereof.

2. The bifunctional polyazamacrocyclic chelating agent according to claim 1 , wherein the chelating agent is of formula (II):

wherein the variables M, L, X, Y, Q 1 , R, m, n and r are as defined above.

3. The bifunctional polyazamacrocyclic chelating agent according to claim 2 , wherein the chelating agent is of formula (III):

wherein the variables M, L, X, Y, R, m, n and r are as defined above.

4. The bifunctional polyazamacrocyclic chelating agent according to claim 3 , wherein the chelating agent is of formula (IV):

wherein the variables M, R, R 1 are as defined above, and u is 1, 2, 3, 4 or 5.

5. The bifunctional polyazamacrocyclic chelating agent according to claim 3 , wherein the chelating agent is of formula (V):

wherein the variables M, R, R 1 are as defined above.

6. The bifunctional polyazamacrocyclic chelating agent according to claim 1 , wherein the chelating agent is of formula (XII):

wherein the variables L, X, Y, Q, Q 1 , m, n and r are as defined above.

7. The bifunctional polyazamacrocyclic chelating agent according to claim 6 , wherein Q is (CHR 5 ) p CO 2 R, wherein R, R 5 and p are as defined in claim 1 .

8. The bifunctional polyazamacrocyclic chelating agent according to claim 6 , wherein the chelating agent is of formula (XIII):

wherein the variables L, X, Y; Q 1 , m, n and r are as defined in claim 1 .

9. The bifunctional polyazamacrocyclic chelating agent according to claim 8 , wherein the chelating agent is of formula (XIV):

wherein the variables L, X, Y, Q 1 , R, m, n and r are as defined in claim 1 .

10. The bifunctional polyazamacrocyclic chelating agent according to claim 9 , wherein the chelating agent is of formula (XV):

wherein the variables R and R 1 arc as defined in claim 1 , and u is 1, 2, 3, 4 or 5.

11. The bifunctional polyazamacrocyclic chelating agent according to claim 10 , wherein the chelating agent is of formula (XVIb):

wherein the variables R and R 1 are as defined in claim 1 .

12. The bifunctional polyazamacrocyclic chalating agent according to claim 1 , wherein R 1 is NO 2 , NH 2 , isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido or carboxyl.