IP Library Granted Patent US 9,314,540
Granted Patent B2
US 9,314,540 · App. 13/880,847 · Granted Apr 19, 2016

Compounds for use in imaging, diagnosing and/or treatment of diseases of the central nervous system

Inventors: Andrea Thiele (Bernau, DE); Georg Kettschau (Berlin, DE); Tobias Heinrich (Berlin, DE); Lutz Lehmann (Berlin, DE); Christer Halldin (Stockholm, SE); Sangram Nag (Huddinge, SE); Andrea Varrone (Bromma, SE); Balazs Gulyas (Solna, SE)
Assignee: PIRAMAL IMAGING SA
A61K51/04C07B59/001C07C211/29
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Quick Facts
Patent No.
US 9,314,540
App. No.
13/880,847
Granted
Apr 19, 2016
Kind
B2
Abstract

This invention relates to novel compounds suitable as precursors for the preparation of certain 18 F labelled positron emission tomography (PET) tracers. Furthermore the invention relates to the preparation of such precursor molecules and to the preparation of PET tracers by 18 F labelling of such precursors.

Claims (64)

1. A compound of formula I:

wherein

D is deuterium;

R 1 is selected from methyl, ethyl, n-propyl, n-butyl, and iso-butyl;

R 2 is [ 18 F]fluorine; and

n and m are each selected from 0 and 1;

with the provisos that:

if n=0, m must be 1, and

if n=1, m must be 0;

including all stereoisomeric forms of said compound, including but not limited to enantiomers and diastereoisomers as well as racemic mixtures,

including salts thereof with an organic or inorganic acids.

2. The compound according to claim 1 , wherein

D is deuterium;

R 1 is methyl; and

R 2 is [ 18 F]fluorine.

3. The compound according to claim 1 , wherein said compound is of formula Ia:

wherein

D is deuterium; and

R 2 is [ 18 F]fluorine;

including enantiomers as well as racemic mixtures, and any suitable salt with an organic or inorganic acid.

4. The compound according to claim 1 , wherein said compound is selected from:

a compound of formula Ic,

wherein F= 18 F,

a compound of formula Ie,

wherein F= 18 F,

and salts thereof with organic or inorganic acids.

5. A diagnostic composition for PET imaging comprising a [ 18 F] labelled compound according to claim 1 .

6. A method of diagnostic PET imaging comprising subjecting a patient to diagnostic PET imaging of CNS diseases, wherein said patient has been administered an [ 18 F] labelled compound according to claim 1 .

7. A method of diagnostic PET imaging comprising subjecting a patient to diagnostic PET imaging of CNS diseases, wherein said patient has been administered a diagnostic composition according to claim 5 .

8. The method according to claim 6 , wherein said patient is imaged for Alzheimer's disease.

9. The method according to claim 6 , wherein said [ 18 F] labelled compound is a compound of formula Ie:

wherein F= 18 F.

10. A method for the synthesis of a compound according to claim 1 :

wherein

D is deuterium;

R 1 is selected from methyl, ethyl, n-propyl, n-butyl, and iso-butyl;

R 2 is [ 18 F]fluorine; and

n is 1 and m is 0;

said method comprising:

reacting a compound of formula I:

wherein

D is deuterium;

R 1 is selected from methyl, ethyl, n-propyl, n-butyl, and iso-butyl;

R 2 is leaving group, wherein said leaving group is selected from halogen, C 1 -C 6 -alkylsulfonyloxy, which is optionally substituted by fluorine, and arylsulfonyloxy, which is optionally substituted by hydrogen, methyl, halo and nitro;

n is 0; and

m is 1;

with a suitable F-fluorinating agent, wherein F is 18 F.

11. The method according to claim 10 for the synthesis of a compound of formula Ic:

wherein F is 18 F,

said method comprising:

reacting a compound of formula Id:

with a suitable F-fluorinating agent, wherein F is 18 F.

12. The method according to claim 10 for the synthesis of a compound of formula le:

wherein F is 18 F,

said method comprising:

reacting a compound of formula If:

with a suitable F-fluorinating agent, wherein F is 18 F.

13. A kit comprising at least one sealed container comprising a compound according to claim 1 .

14. A kit comprising at least one sealed container comprising a compound of claim 4 .

15. The kit according to claim 13 , further comprising a further sealed container comprising reagents.

16. The compound according to claim 1 , wherein n is 0 and m is 1.

17. The compound according to claim 1 , wherein n is 1 and m is 0.

18. The compound according to claim 1 , wherein said compound is a salt of a compound of formula I with an acid selected from carbonic, nitric, phosphoric, hydrochloric, perchloric, sulfuric, formic, acetic, trifluoracetic, propionic, succinic, glycolic, gluconic, lactic, malic, fumaric, pyruvic, benzoic, anthranilic, mesylic, fumaric, salicylic, phenylacetic, mandelic, embonic, methansulfonic, ethanesulfonic, benzenesulfonic, phantothenic, toluenesulfonic, trifluormethansulfonic and sulfanilic acids.

19. The compound according to claim 1 , wherein said compound is:

Assignments (4)
CHANGE OF ADDRESS Recorded Feb 9, 2023
From: LIFE MOLECULAR IMAGING LIMITED
To: LIFE MOLECULAR IMAGING LIMITED
Reel/Frame 064124/0514 →
NUNC PRO TUNC ASSIGNMENT Recorded Mar 11, 2022
From: LIFE MOLECULAR IMAGING SA
To: LIFE MOLECULAR IMAGING LIMITED
Reel/Frame 059861/0901 →
CHANGE OF NAME Recorded May 22, 2019
From: PIRAMAL IMAGING SA
To: LIFE MOLECULAR IMAGING SA
Reel/Frame 049252/0547 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 30, 2013
From: THIELE, ANDREA; KETTSCHAU, GEORG; HEINRICH, TOBIAS; LEHMANN, LUTZ; HALLDIN, CHRISTER; NAG, SANGRAM; VARRONE, ANDREA; GULYAS, BALAZS
To: PIRAMAL IMAGING SA
Reel/Frame 031116/0127 →
Priority Claims (1)
EP 10188559 · Oct 22, 2010 · regional
Continuity (1)
Related Publication 20130336890A1 · Dec 19, 2013