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US 7,115,766 B2Granted
Nucleophilic approach for preparing radiolabeled imaging agents and associated compounds
AssigneeIndiana University Research and Technology Corporation
InventorsG. Keith Mulholland, Martin J. O'Donnell, Frederick T. Chin, Francisca Delgado
Life of this patent
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Abstract
Radiolabeled fluorinated compounds useful for imaging in the diagnosis of Parkinson's Disease are disclosed. Methods and kits for their synthesis are also disclosed.
Claims15
A compound having the formula:
- wherein R1 is hydrogen, acyloxymethyl of 1–4 carbons, formyl, acyl, polyfluoroacyl of 2–3 carbons, optionally substituted alkyl and aryl sulfonyl, optionally substituted alkyl and aryl phosphoryl, or R1 together with R4 and —N—Cα—C(O)— forms a 4–7 membered ring, with bridging atoms being C, O, N, P, or S, or combinations thereof;
- R2 is hydrogen, C2–C7 normal, branched, cyclic saturated, cyclic unsaturated alkyl and alkoxyalkyl, optionally substituted tert-butyloxycarbonyl, optionally substituted benzyloxycarbonyl, formyl, acyl, polyfluoroacyl of 2–3 carbons, optionally substituted alkyl and aryl sulfonyl, or optionally substituted alkyl and aryl phosphoryl;
- R4 is OtBu, OCH3, C2–C7 normal, branched, cyclic saturated, cyclic unsaturated alkoxy, and or R4 together with R1 and —N—CαC(O)— forms a 4–7 membered ring, with bridging atoms being C, O, N, P, or S, or combinations thereof;
- X is halogen, NO2, N2+, N+(CH3)3, S+(CH3)2, or aryl iodonium;
- Y is hydrogen, fluorinated alkyl, or NO2;
- Z is fluorinated alkyl or NO2;
- and
- R5 is hydrogen, OtBu, OCH3, C2–C7 normal, branched, cyclic saturated, or cyclic unsaturated alkoxy, acyl, halogen, azide or acylamide.
5 more elements
A compound having the formula:
- wherein X is a leaving group which allows nucleophilic radiofluorination at the position of X in the presence of soluble reactive [18F]fluoride ion;
- Y is a radical which contains one or more electron-withdrawing groups that result in an oxygen directly attached to the aromatic ring para to leaving group X when said compound is subjected to a Baeyer-Villiger Reaction;
- R1 is hydrogen, acyloxymethyl of 1–4 carbons, formyl, acyl, polyfluoroacyl of 2–3 carbons, optionally substituted alkyl and aryl sulfonyl, optionally substituted alkyl and aryl phosphoryl, or R1 together with R4 and —N—Cα—C(O)— forms a 4–7 membered ring, with bridging atoms being C, O, N, P, or S, or combinations thereof;
- R2 is hydrogen, C2–C7 normal, branched, cyclic saturated, cyclic unsaturated alkyl and alkoxyalkyl, optionally substituted tert-butyloxycarbonyl, optionally substituted benzyloxycarbonyl, formyl, acyl, polyfluoroacyl of 2–3 carbons, optionally substituted alkyl and aryl sulfonyl, or optionally substituted alkyl and aryl phosphoryl;
- R4 is OtBu, OCH3, C2–C7 normal, branched, cyclic saturated, cyclic unsaturated alkoxy, or R4 together with R1 and —N—Cα—C(O)— forms a 4–7 membered ring, with bridging atoms being C, O, N, P, or S, or combinations thereof;
- R5 is hydrogen or a radical that can be converted to a phenolic OH group during or after said Baeyer-Villiger Reaction.
3 more elements
A kit for providing a radiolabeled Positron Emission Tomography imaging agent, said kit comprising:
- a first container which contains a compound having the formula
- wherein X is a leaving group which allows nucleophilic radiofluorination at the position of X in the presence of soluble reactive [18F]fluoride ion;
- Y is a radical which contains one or more electron-withdrawing groups that result in an oxygen directly attached to the aromatic ring para to leaving group X when said compound is subjected to a Baeyer-Villiger Reaction;
- R1 is hydrogen, acyloxymethyl of 1–4 carbons, formyl, acyl, polyfluoroacyl of 2–3 carbons, optionally substituted alkyl and aryl sulfonyl, optionally substituted alkyl and aryl phosphoryl, or R1 together with R4 and —N—Cα—C(O)— forms a 4–7 membered ring, with bridging atoms being C, O, N, P, or S, or combinations thereof;
- R2 is hydrogen, C2–C7 normal, branched, cyclic saturated, cyclic unsaturated alkyl and alkoxyalkyl, optionally substituted tert-butyloxycarbonyl, optionally substituted benzyloxycarbonyl, formyl, acyl, polyfluoroacyl of 2–3 carbons, optionally substituted alkyl and aryl sulfonyl, or optionally substituted alkyl and aryl phosphoryl;
- R4 is OtBu, OCH3, C2–C7 normal, branched, cyclic saturated, cyclic unsaturated alkoxy, or R4 together with R1 and —N—Cα—C(O)— forms a 4–7 membered ring, with bridging atoms being C, O, N, P, or S, or combinations thereof;
- and
- R5 is hydrogen or a radical that can be converted to a phenolic OH group during or after said Baeyer-Villiger Reaction;
- and
- a second container which contains a polar aprotic solvent for dissolving said compound.
7 more elements
Dependencies are inferred from the claim text.