Deoxycytidine kinase binding compounds

1. A compound of the formula (I):

or a salt thereof, wherein:

R 1 and R 2 are independently H, OH, OR 14 , NH 2 , NHC(O)R 15 or NHC(O)OR 17 ;

each Y 1 , Y 2 and Y 3 is independently N or CH, wherein at least one of Y 1 , Y 2 , and Y 3 is N;

L is O, S, SO, SO 2 , Se, NH or NR 16 ;

each m, n, p, q and r is independently 1, 2, 3, 4, 5 or 6;

n′ is 0, 1, 2, 3, 4, 5 or 6;

R 3 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, aryl, heteroaryl or OCH 3 ;

R 4 and R 8 are independently H, F, Cl, Br, I, CF 3 or OR 9 ;

R 5 and R 7 are independently H, F, Cl, Br, I, CF 3 , fluoropyridyl or OR 10 ;

Z is N or CR 6 ;

R 6 is H, F, Cl, Br, I, CF 3 or OR 11 ;

R 9 and R 11 are independently C 1 -C 6 alkyl, C 1 -C 6 perfluoroalkyl, (CH 2 ) m X, (CH 2 ) p OR 12 , or (CH 2 ) r X*,

R 10 is C 1 -C 6 alkyl, C 1 -C 6 perfluoroalkyl, (CH 2 ) m X, (CH 2 ) p OR 12 , (CH 2 ) q R 13 or (CH 2 ) r X*;

R 12 is H, tosyl or 2-tetrahydropyranyl;

R 13 is OCH 3 , NH 2 , NHCOCH 3 , CO 2 H, CO 2 CH 3 , SH or COCH 3 ;

R 14 is C 1 -C 4 alkyl;

R 15 is C 1 -C 6 alkyl or CF 3 ;

R 16 is C1-C4 alkyl or phenyl;

R 17 is C 1 -C 6 alkyl;

X is F, Cl, Br or I; and

X* is 18 F, 75 Br, 76 Br or 124 I.

2. The compound of claim 1 , wherein R 1 and R 2 are independently H, NH 2 , NHC(O)R 15 or NHC(O)OR 17 ; or a salt thereof.

3. The compound of claim 2 , wherein each R 1 and R 2 is NH 2 ; or a salt thereof.

4. The compound of claim 2 , wherein each R 1 and R 2 is NHC(O)R 15 ; or a salt thereof.

5. The compound of claim 4 , wherein R 15 is CH 3 ; or a salt thereof.

6. The compound of claim 4 , wherein R 15 is CF 3 ; or a salt thereof.

7. The compound of claim 1 , wherein R 5 is F, Cl, Br, I, CF 3 , fluoropyridyl or OR 10 ; or a salt thereof.

8. The compound of claim 7 , wherein R 5 is OR 10 ; or a salt thereof.

9. The compound of claim 8 , wherein R 10 is C 1 -C 6 alkyl, C 1 -C 6 perfluoroalkyl, (CH 2 ) m X, (CH 2 ) p OR 12 or (CH 2 ) r X*; or a salt thereof.

10. The compound of claim 9 , wherein R 10 is (CH 2 ) r X*; or a salt thereof.

11. The compound of claim 10 , wherein X* is 18 F; or a salt thereof.

12. The compound of claim 1 , wherein the compound is of the formula (A):

or a salt thereof, wherein:

R 1 and R 2 are independently NH 2 , OH, OCH 3 or OC 2 H 5 ;

each Y 1 , Y 2 and Y 3 is independently N or CH, wherein at least one of Y 1 , Y 2 , and Y 3 is N;

n is 1, 2, 3, 4, 5 or 6;

n′ is 0, 1, 2, 3, 4, 5 or 6;

R 3 is CH 3 , C 2 H 5 , C 3 H 7 or OCH 3 ;

each R 4 , R 5 , R 6 , R 7 and R 8 is independently H, F, Cl, Br, I or OR 9 ;

each R 9 is independently CH 3 , C 2 H 5 , C 3 H 7 , C 4 H 9 , C 5 H 11 , C 6 H 13 , CH 2 F, C 2 H 4 F, C 3 H 6 F, C 4 H 8 F, C 5 H 10 F, C 6 H 12 F, C 2 H 4 Br, C 2 H 4 I, CF 3 , C 2 F 5 , C 3 F 7 , C 4 F 9 , C 5 F 11 , C 6 F 13 , CH 2 OTs, C 2 H 4 OTs, C 3 H 6 OTs, C 4 H 8 OTs, C 5 H 10 OTs, C 6 H 12 OTs, CH 2 OH, C 2 H 4 OH, C 3 H 6 OH, C 4 H 8 OH, C 5 H 10 OH, C 6 H 12 OH, CH 2 OTHP, C 2 H 4 OTHP, C 3 H 6 OTHP, C 4 H 8 OTHP, C 5 H 10 OTHP or C 6 H 12 OTHP, CH 2 X*, C 2 H 4 X*, C 3 H 6 X*, C 4 H 8 X*, C 5 H 10 X*, C 6 H 12 X*;

wherein Ts is tosyl;

wherein THP is 2-tetrahydropyranyl group; and

wherein X* is selected from: 18 F, 75 Br, 76 Br or 124 I.

13. The compound of claim 1 , wherein the compound binds to a deoxycytidine kinase polypeptide.

14. The compound of claim 1 , or a salt thereof, and a pharmaceutically acceptable carrier.

15. A method for inhibiting a deoxycytidine kinase (dCK) activity comprising contacting a compound of claim 1 with the deoxycytidine kinase.

16. A compound, or salt thereof, wherein the compound is selected from the group consisting of:

17. A method of imaging, comprising:

administering a radiolabeled compound of claim 1 to an animal or human;

performing PET imaging to determine a local concentration of the compound in the animal or human; and

correlating the local concentration of the compound with a local immune response or the presence of neoplastic tissue.

18. The method of claim 17 , further comprising using the local concentration of the compound to diagnose cancer and/or monitor cancer treatment.

19. The method of claim 17 , wherein the animal or human has a condition selected from the group consisting of cancer, an autoimmune disorder, a development disorder, viral infection, bacterial infection, parasitical infection, infection, a metabolic disease, and inflammation.

20. The method of claim 17 , wherein the animal or human is undergoing a therapy selected from the group consisting of cancer immunotherapy, immunotherapy, interferon therapy, vaccination, radiation therapy, chemotherapy, and antibiotic therapy.