Compounds for use in imaging, diagnosing and/or treatment of diseases of the central nervous system or of tumors
This invention relates to novel compounds suitable for labelling or already labelled by 18 F, methods of preparing such a compound, compositions comprising such compounds, kits comprising such compounds or compositions and uses of such compounds, compositions or kits for diagnostic imaging by positron emission tomography (PET).
1. A compound of formula Ib
wherein
W is —C(U 1 )(U 2 )—C≡CH,
U 1 and U 2 are each being independently selected from hydrogen and deuterium,
G 3 is hydrogen,
G 4 is L,
L is a leaving group or is F,
n is an integer from 0 to 6, and
e and f are each independently an integer from 0 to 1, with the proviso that at least one of e and f is 1,
including all isomeric forms of said compound, including but not limited to enantiomers and diastereoisomers as well as racemic mixtures,
or a pharmaceutically acceptable salt, ester, amide, complex or prodrug thereof.
2. The compound according to claim 1 , wherein W is —CH 2 —C≡CH.
3. The compound according to claim 1 , wherein L is a leaving group selected from halo, mesyloxy, tosyloxy, trifluormethylsulfonyloxy, nona-fluorobutylsulfonyloxy, (4-bromo-phenyl)sulfonyloxy, (4-nitro-phenyl)sulfonyloxy, (2-nitro-phenyl) sulfonyloxy, (4-isopropyl-phenyl) sulfonyloxy, (2,4,6-tri-isopropyl-phenyl)sulfonyloxy, (2,4,6-trimethyl-phenyl)sulfonyloxy, (4-tertbutyl-phenyl)sulfonyloxy, and (4-methoxy-phenyl)sulfonyloxy.
4. The compound according to claim 3 , wherein L is selected from chloro, bromo, mesyloxy, tosyloxy, trifluormethylsulfonyloxy, (4-bromo-phenyl)sulfonyloxy, (4-nitro-phenyl)sulfonyloxy, (4-isopropyl-phenyl)sulfonyloxy, and (2,4,6-tri-isopropyl-phenyl) sulfonyloxy.
5. The compound according to claim 1 wherein L is a leaving group.
6. The compound according to claim 1 , wherein L is 18 F.
7. The compound according to claim 1 , wherein L is 19 F.
8. A method of synthesis of a compound according to claim 1 wherein L is 18 F or 19 F, said method comprising reacting a compound according to formula 1b in which L is a leaving group with an F-fluorinating agent in which F is 18 F or 19 F.
9. The method according to claim 8 , wherein said F-fluorinating agent is selected from 4, 7, 13, 16, 21, 24-hexaoxa-1,10-diazabicyclo[8.8.8]-hexacosane KF, KF, HF, KH F 2 , CsF, NaF and tetraalkylammonium salts of F, and wherein F= 18 F or 19F.
10. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or diluent.
11. A composition comprising a compound according to claim 6 and a pharmaceutically acceptable carrier or diluent.
12. A composition comprising a compound according to claim 7 and a pharmaceutically acceptable carrier or diluent.
13. A compound according to claim 1 for use as a pharmaceutical or diagnostic agent or imaging agent.
14. A compound according to claim 6 for use as a diagnostic agent or imaging agent.
15. A kit comprising a sealed vial containing a predetermined quantity of a compound according to claim 5 .
16. A method for detecting the presence of monoamine oxidase in a patient's body comprising:
introducing into a patient's body a detectable amount of a compound according to claim 6 , and
detecting said compound by positron emission tomography (PET).
17. A method of treatment of a disease of the central nervous system associated with monoamine oxidase regulation, said method comprising the step of introducing into a patient a suitable quantity of a compound according to claim 1 .
18. A compound according to claim 1 , wherein L is 18 F or 19 F.
19. A compound according to claim 1 , wherein n is an integer from 0 to 3.
20. A compound according to claim 1 , wherein n is an integer from 0 to 2.
21. The compound according to claim 1 , wherein L is a leaving group selected from chloro, bromo, iodo, mesyloxy, tosyloxy, trifluormethylsulfonyloxy, nona-fluorobutylsulfonyloxy, (4-bromo-phenyl)sulfonyloxy, (4-nitro-phenyl)sulfonyloxy, (2-nitro-phenyl)sulfonyloxy, (4-isopropyl-phenyl)sulfonyloxy, (2,4,6-tri-isopropyl-phenyl)sulfonyloxy, (2,4,6-trimethyl-phenyl)sulfonyloxy, (4-tertbutyl-phenyl)sulfonyloxy, and (4-methoxy-phenyl) sulfonyloxy.
22. The compound according to claim 1 , wherein said compound is:
23. A method for preparing a compound according to claim 1 , comprising reacting a compound selected from the following compounds:
with an F-fluorinating agent.
24. The method according to claim 16 , wherein said method is for imaging a disease of the central nervous system in said patient.
25. The method according to claim 17 , wherein L in said compound is 18 F.
26. The method according to claim 17 , wherein L in said compound is 19 F.
27. The compound according to claim 1 , wherein U 1 and U 2 are each deuterium.
28. The method according to claim 8 , wherein said F-fluorinating agent is 4,7,13,16,21,24-Hexaoxa-1,10-diazabicyclo[8.8.8]-hexacosane OF, OF, H 18 F, KH 18 F 2 , Cs 18 F, Na 18 F or a tetraalkylammonium salt of 18 F.
29. The compound according to claim 1 , wherein said compound is selected from the following compounds:
30. The compound according to claim 1 , wherein said compound is selected from the following compounds:
31. The compound according to claim 1 , wherein said compound is selected from the following compounds:
32. The compound according to claim 1 , wherein said compound is selected from the following compounds in which the H atoms in the —CH 2 — group of the —CH 2 —C≡CH structure are replaced by deuterium:
33. The compound according to claim 1 , wherein said compound is selected from the following compounds in which the H atoms in the —CH 2 — group of the —CH 2 —C≡CH structure are replaced by deuterium:
34. The compound according to claim 1 , wherein said compound is selected from the following compounds in which the H atoms in the —CH 2 — group of the —CH 2 —C≡CH structure are replaced by deuterium: