Bridgehead labelled compounds and methods of using the same
View Patent ↗The present invention relates to compounds having the general formula: Y-L-BFR-X wherein BFR is a bridged fused ring system; Y is a targeting group; L is optionally present and is a linker for coupling Y to BFR; and X is halogen (e.g., radiohalogen) or a functional group for labelling.
1. A compound having the general formula:
Y-L-BFR-X
wherein
BFR is a bridged fused ring system;
Y is a targeting group;
L is optionally present and is a linker for coupling Y to BFR; and
X is coupled to a bridgehead atom of BFR and is selected from the group consisting of:
halogens other than bromine and iodine;
a CH 2 F group optionally labelled with 18 F; and
—CH 2 OSO 2 R, —OSO 2 R, —Sn(alkyl) 3 and —Pb(alkyl) 3 , wherein R is selected from the group consisting of —CH 3 , —CF 3 , —(C 6 H 4 )CH 3 , and —(C 6 H 4 )NO 2 .
2. A compound having the general formula:
Y-L-BFR-X
wherein
BFR is a bridged fused ring system other than an adamantane fused ring system;
Y is a targeting group;
L is optionally present and is a linker for coupling Y to BFR; and
X is selected from the group consisting of halogen, a CH 2 F group optionally labelled with 18 F, —OH, —CH 2 OSO 2 R, —OSO 2 R, —Sn(alkyl) 3 and —Pb(alkyl) 3 , wherein R is selected from the group consisting of —CH 3 , —CF 3 , —(C 6 H 4 )CH 3 , and —(C 6 H 4 )NO 2 , wherein X is coupled to a bridgehead atom of BFR.
3. The compound of claim 2 , wherein X is selected from the group consisting of 123 I, 124 I, 131 I, 76 Br, 77 Br, and 82 Br.
4. The compound of claim 2 , wherein X is 123 I.
5. The compound of claim 2 , wherein X is —OH, —Br or —I.
6. The compound of claim 2 , wherein BFR is selected from the group consisting of bicyclooctane, norbornane and cubane.
7. The compound of claim 2 , wherein BFR is cubane.
8. The compound of claim 2 , wherein X is non-radioactive.
9. The compound of claim 2 , wherein X is radioactive.
10. The compound of claim 9 , wherein X is 18 F or 211 At.
11. The compound of claim 2 , wherein X is selected from the group consisting of —OSO 2 R, —Sn(alkyl) 3 and —Pb(alkyl) 3 , and wherein R is selected from the group consisting of —CH 3 , —CF 3 , —(C 6 H 4 )CH 3 , and —(C 6 H 4 )NO 2 .
12. The compound of claim 2 , wherein X is a CH 2 F group optionally labelled with 18 F.
13. The compound of claim 2 , wherein X is —CH 2 OSO 2 R, and wherein R is selected from the group consisting of —CH 3 , —CF 3 , —(C 6 H 4 )CH 3 , and —(C 6 H 4 )NO 2 .
14. The compound of claim 2 , wherein L is present and is selected from the group consisting of —(CO)—, —O(CO)—, —NH(CO)—, —NH—, —O(CH 2 ) n —, —NH(CH 2 ) n —, —NH(CO)NH—, and —NH(CS)NH—.
15. The compound of claim 2 , wherein BFR is a bridged fused ring system having a skeleton of only carbon atoms.
16. The compound of claim 2 , wherein BFR is a bridged fused ring system comprising at least one heteroatom.
17. The compound of claim 2 , wherein Y is selected from group consisting of amino acids, peptidomimetics, nucleic acids, RNA, DNA, nucleosides, nucleotides, carbohydrates, glycomimetics, lipids, phospholipids, hormones, neurotransmitters, and vitamins.
18. The compound of claim 2 , wherein the compound has the formula:
wherein BFR and X are as defined in claim 2 .
19. The compound of claim 17 , wherein Y is N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)pyridin-2-amine.
20. The compound of claim 2 , wherein Y is selected from group consisting of proteins, peptides, enzymes, antibodies and fragments thereof.
21. The compound of claim 2 , wherein Y is selected from group consisting of polyaminoacids, polyols, polyamines, polyacids, oligonucleotides, aborols, dendrimers and aptamers.