Dopamine transporter imaging agent
AssigneesOrganix, Inc., President and Fellows of Harvard College, Massachusetts Institute of Technology
InventorsPeter C. Meltzer, Bertha K. Madras, Alan Davison, Paul Blundell, Ashfaq Mahmood, Alun G. Jones
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Abstract
Radiopharmaceutical compounds are disclosed. A tropane compound is linked through the N atom at the 8-position to a chelating ligand capable of complexing technetium or rhenium to produce a neutral labeled complex that selectively binds to the dopamine transporter. These compounds can be prepared as separate diastereoisomers as well as a mixture of diastereoisomers. Also disclosed are radiopharmaceutical kits for preparing the labeled radiopharmaceutical compounds.
Claims30
A radiopharmaceutical compound which is capable of complexing with 99mTc, said compound having the following structural formula:
- wherein
- R1 is selected from COORa, CORa, CONHRa, CONRaRb, CH2CH3, (CH2)nCH3, CHCHRc, (CH2)nCCRc or an ester bioisostere;
- R2 is selected from C6H4X, C6H3X2, C10H6X, or C12H8WYCHO (diarylmethoxy);
- Ra and Rb are each selected from CH3, CH2CH3, CH2CH2CH3, (CH2)nCH3, CH(CH3)2, C(CH3)3, (CH2)nC6H5, C6H5, C6H4X, C10H7, or C10H6X;
- Rc is selected from COORa, CH3, (CH2)nCH3, C6H5, C6H4X, C10H7, or C10H6X;
- X is selected from H, Br, Cl, I, F, OH, OCH3, CF3, NO2, NH2, CN, OR, NHCOCH3, N(CH3)2, CH2CH3, CHOCH3, C(CH3)3;
- W and Y are each selected from H, Br, Cl, I, F, OH, OCH3, CF3, NO2, NH2, CN, OR, NHCOCH3, N(CH3)2;
- n is an integer 0-6;
- L is a linking moiety comprising a chain of atoms containing 2 to about 6 carbon atoms in the backbone of the chain or, if a ring is part of the chain, 1 to about 4 carbon atoms in the backbone of the chain in addition to the ring carbons;
- and
- Ch is a tridentate or tetradentate chelating ligand capable of forming a neutral complex with technetium or rhenium.
N-2-((31-N′-propyl-(1″R-3″β-(4-fluorophenyl)tropane-2″β-carboxylic acid methyl ester))((2-((triphenylmethyl)thio)-ethyl)amino)acetyl)-S-(triphenylmethyl)-2-aminoethanethiol.
N-2-((3′-N′-propyl-(1″R-3″β-(3,4-dichlorophenyl)tropane-2″β-carboxylic acid methyl ester))((2-((triphenylmethyl)thio)ethyl)amino)acetyl)-S-(triphenylmethyl)-2-aminoethanethiol.
N-2-((3′-N′-propyl-(1″S-3″α-((bis(4-fluorophenyl)methoxyl)tropane-2″β-carboxylic acid methyl ester))((2-((triphenylmethyl)thio)ethyl)amino)acetyl)-S-(triphenylmethyl)-2-aminoethanethiol.
(RS)-N-{2-((3′-N′-propyl-(1″R-3″β-(4-fluorophenyl)tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide.
(RS)-N-{2-((3′-N′-propyl-(1″R-3″β-(4-fluorophenyl)tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato}rhenium (V) Oxide.
(RS)-N-2-((3′-N′-propyl-(1″R-3″β-(4-fluorophenyl)tropane-2″α-carboxylic acid methyl ester))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiol.
(RS)-N-{2-((3′-N′-propyl-(1″R-3″β-(4-fluorophenyl)-tropane-2″α-carboxylic acid methyl ester))(2-mercaptoethyl) amino)acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide.
(RS)-N-{2-((3′-N′-propyl-(1″R-3″β-(4-fluorophenyl)-tropane-2″α-carboxylic acid methyl ester))(2-mercaptoethyl) amino)acetyl)-2-aminoethanethiolato}rhenium (V) Oxide.
(RS)-N-2-((3′-N′-propyl-(1″R-3″β-(3,4-dichlorophenyl)-tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl) amino)acetyl)-2-aminoethanethiol.
(RS)-N-{2-((3′-N′-propyl-(1″R-3″β-(3,4-dichlorophenyl)-tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl) amino)acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide.
(RS)-N-{2-((3′-N′-propyl-(1″R-3″β-(3,4-dichlorophenyl)-tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl) amino)acetyl)-2-aminoethanethiolato}rhenium (V) Oxide.
(RS)-N-2-((3′-N′-propyl-(1″S-3″α-((bis(4-fluorophenyl)methoxy)tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl)amino)acetyl)-2-aminoethanethiol.
(RS)-N-{2-((3′-N′-propyl-(1″S-3″α-((bis(4-fluorophenyl)methoxy)tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl)amino)acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide.
(RS)-N-{2-((3′-N′-propyl-(1″S-3″α-((bis(4-fluorophenyl)methoxy)tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl)amino)acetyl)-2-aminoethanethiolato}rhenium (V) Oxide.
A radiopharmaceutical compound selected from the group consisting of (R)-N-{2-((3′-N′-propyl-(1″R-3″β-(4-fluorophenyl)tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide, (R)-N-{2-((3′-N′-propyl-(1″R-3″-(4-fluorophenyl)-tropane-2″α-carboxylic acid methyl ester))(2-mercaptoethyl) amino)acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide, (R)-N-{2-((3′-N′-propyl-(1″R-3″β-(3,4-dichlorophenyl)-tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl) amino)acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide, and (R)-N-{2-((3′-N′-propyl-(1″S-3″α-((bis(4-fluorophenyl)methoxy)tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl)amino)acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide.
A radiopharmaceutical compound selected from the group consisting of (S)-N-{2-((3′-N′-propyl-(1″R-3″β-(4-fluorophenyl)tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl)amino)-acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide, (S)-N-{2-((3′-N′-propyl-(1″R-3″β-(4-fluorophenyl)-tropane-2″α-carboxylic acid methyl ester))(2-mercaptoethyl) amino)acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide, (S)-N-{2-((3′-N′-propyl-(1″R-3″β-(3,4-dichlorophenyl)-tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl) amino)acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide, and (S)-N-{2-((3′-N′-propyl-(1″S-3″α-((bis(4-fluorophenyl)methoxy)tropane-2″β-carboxylic acid methyl ester))(2-mercaptoethyl)amino)acetyl)-2-aminoethanethiolato}99mtechnetium (V) Oxide.
Dependencies are inferred from the claim text.