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Upstream product

• 67-56-1 methanol 
• 130342-81-3 RTI-32 
• 4294-57-9 para-methylphenylmagnesium bromide 
• 481-37-8 ecgonine 
• 53-21-4 (-)-cocaine hydrochloride 
• 50373-10-9 methyl ecgonidine 

Downstream Products

• 440370-74-1 2β-carbomethoxy-3β-p-tolyl-N-(p-tolylsulfonamide)-tropane 
• 877467-20-4 [3H]-LBT-999 
• 263841-47-0 (1R,2S,3S,5S)-8-Ethoxycarbonylmethyl-3-p-tolyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester 
• 1179817-50-5 methyl 8-(((1S,2S)-2-(fluoromethyl)cyclopropyl)methyl)-3-p-tolyl-8-azabicyclo[3.2.1]octane-2-carboxylate 
• 1179817-55-0 methyl 8-(((1R,2R)-2-(fluoromethyl)cyclopropyl)methyl)-3-p-tolyl-8-azabicyclo[3.2.1]octane-2-carboxylate 
• 1179817-46-9 PR_04.MZ 
• 1192248-75-1 2-exo-carboxymethyl-3-(4-methylphenyl)-8-(4'-hydroxybut-2-ynyl)-8-azabicyclo[3.2.1]octane 
• 1192740-59-2 methyl 8-[(E)-4-hydroxybut-2-enyl]-3-p-tolyl-8-azabicyclo[3.2.1]octane-2-carboxylate 
• 1192248-77-3 [18F]PR_04.MZ 
• 440370-77-4 2β-[3,4-(methylenedioxy)phenoxy]methyl-3β-p-tolyl-N-(p-tolylsulfonamide)-tropane 
• 440370-76-3 2β-trifluoromethanesulfonyloxymethyl-3β-p-tolyl-N-(p-tolylsulfonamide)-tropane 
• 440370-75-2 2β-hydroxymethyl-3β-p-tolyl-N-(p-tolylsulfonamide)-tropane 
• 440370-69-4 2β-[3,4-(methylenedioxy)phenoxy]methyl-3β-p-tolyl-nortropane 
• 263841-49-2 (1S,3S,4S,8R)-3-p-Tolyl-7-aza-tricyclo[5.3.0.0^4,8]decan-5-one 

Relevant academic research and scientific papers

68Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System

The development of radiometal-labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood–brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of 68Ga-labelled phenyltropanes showing that, through a simple hydrocarbon-linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequate lipophilicity. One of the candidates, [68Ga]Ga-HBED-hexadiyne-tropane, showed an IC50 value of 66 nM, together with a log D7.4 of 0.96. A μPET study in a hemi-parkinsonian rat model showed a fast wash-out of the tracer, and no specific uptake in the brain, thus implying an inability to penetrate the BBB.

[11C]PR04.MZ, a promising DAT ligand for low concentration imaging: Synthesis, efficient 11C-O-methylation and initial small animal PET studies

PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [11C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [11C]MeI mediated synthesis of [11C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb2CO3 in DMF in up to 95 ± 5% labelling yield. A preliminary μPET-experiment demonstrates the reversible, highly specific binding of [11C]PR04.MZ in the brain of a male Sprague-Dawley rat.

Synthesis and monoamine uptake inhibition of conformationally constrained 2β-carbomethoxy-3β-phenyl tropanes

A series of 2β-carbomethoxy-3β-phenyl tropanes with conformationally constrained nitrogen substituents were synthesized as potential selective dopamine transporter ligands. These novel compounds were examined for their monoamine uptake inhibition potency at the human dopamine transporter (hDAT), the human serotonin transporter (hSERT) and the human noradrenalin transporter (hNET), stably expressed in human embryonic kidney cells (HEK). A SAR-study was conducted to determine the contribution of extended, 4-fluorinated, conformationally constrained C4 chains at the tropane nitrogen to human monoamine transporter affinity and selectivity. The Royal Society of Chemistry 2009.

METHOD OF FLUORINE-18 LABELLING OF TROPANE DERIVATIVES

The invention relates to a one-step [18F]radiolabelling process of tropanamine derivatives which are useful for imaging the neuronal dopamine transporter (DAT) with Positron Emission Tomography (PET).

Synthesis and monoamine transporter affinity of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position

A series of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position was synthesized, and their binding affinities were determined in cells transfected to express human nor

Rearrangement of a mesylate tropane intermediate in nucleophilic substitution reactions. Synthesis of aza-bicyclo[3.2.1]octane and aza-bicyclo[3.2.2]nonane ethers, imides, and amines.

Nucleophilic substitution of 2beta-mesyloxymethyl-N-methyl-3beta-p-tolyl-tropane intermediate with alkoxides, metal imides, or amines was found to lead not only to the expected bicyclo[3.2.1]octane (tropane) ether, imide, and amine derivatives but also to unexpected bicyclo[3.2.2]nonane derivatives. When alkoxides were used as nucleophile, only the rearranged bicyclo[3.2.2]nonane structure was obtained, whereas the use of amines or imides as nucleophile afforded a mixture of the two structures. The bicyclo[3.2.2]nonane structure was assigned by NMR analysis.

Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: Potential positron emission tomography (PET) imaging agents for the dopamine transporter

A series of novel fluoroalkyl-containing tropane derivatives was synthesized, and their binding affinities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined via competitive binding assays. Among these derivatives, the fluoropropyl ester of β-CIT (19), the fluoroethyl ester of β-CIT (20), the N-fluoropropyl derivative of β-CBT (12), and the fluoropropyl ester of β-CMT (18) displayed higher affinity and greater selectivity for the DAT versus SERT and NET than FP-CIT, which indicates that they are attractive candidates for the development of 18F-labeled PET imaging agents for the DAT.

3alpha-(4-Substituted phenyl)nortropane-2beta-carboxylic acid methyl esters show selective binding at the norepinephrine transporter.

A series of 3alpha-(4-substituted)nortropane-2beta-carboxylic acid methyl esters was synthesized and evaluated for the ability to inhibit radioligand binding at the dopamine, serotonin, and norepinephrine transporters. 3alpha-(4-Methylphenyl)nortropane-2beta-carboxylic acid methyl ester (4c) was found to be selective and highly potent for the norepinephrine transporter (NET) relative to the dopamine and serotonin transporters.