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Papers by Zhude Tu
Journal of Medicinal Chemistry, 2011
A series of fluorine containing N-(2-methoxyphenyl)piperazine and N-(2-fluoroethoxy)piperazine an... more A series of fluorine containing N-(2-methoxyphenyl)piperazine and N-(2-fluoroethoxy)piperazine analogues were synthesized and their affinities for human dopamine D 2 , D 3 and D 4 receptors were determined. Radioligand binding studies identified five compounds, 18a, 20a, 20c, 20e and 21e, which bind with high affinity at D 3 (K i = 0.17 to 5 nM) and moderate to high selectivity for D 3 vs. D 2 receptors (ranging from ∼25 to 163-fold). These compounds were also evaluated for intrinsic activity at D 2 and D 3 receptors using a forskolin-dependent adenylyl cyclase assay. This panel of compounds exhibits varying receptor subtype binding selectivity and intrinsic activity at D 2 vs. D 3 receptors. These compounds may be useful for behavioral pharmacology studies on the role of D 2like dopamine receptors in neuropsychiatric and neurological disorders. Furthermore, compound 20e, which has the highest binding affinity and selectivity for the D 3 receptor (K i = 0.17 nM for D 3 , 163-fold selectivity for D 3 vs. D 2 receptors) represents a candidate fluorine-18 radiotracer for in vivo PET imaging studies on the regulation of D 3 receptor expression.
![Research paper thumbnail of Radiosynthesis and in vivo evaluation of [11C]MP-10 as a PET probe for imaging PDE10A in rodent and non-human primate brain](https://attachments.academia-assets.com/79848698/thumbnails/1.jpg)
](Bioorganic & Medicinal Chemistry, 2011
2-((4-(1-[11C]Methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-quinoline (MP-10), a specif... more 2-((4-(1-[11C]Methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-quinoline (MP-10), a specific PDE10A inhibitor (IC50=0.18nM with 100-fold selectivity over other PDEs), was radiosynthesized by alkylation of the desmethyl precursor with [11C]CH3I, ∼45% yield, >92% radiochemical purity, >370GBq/μmol specific activity at end of bombardment (EOB). Evaluation in Sprague–Dawley rats revealed that [11C]MP-10 had highest brain accumulation in the PDE10A enriched-striatum, the 30min striatum: cerebellum ratio reached 6.55. MicroPET studies
Bioorganic & medicinal …, 2005
A series of N-(2-methoxyphenyl) piperazine and N-(2, 3-dichlorophenyl) piperazine analogs were pr... more A series of N-(2-methoxyphenyl) piperazine and N-(2, 3-dichlorophenyl) piperazine analogs were prepared and their affinities for dopamine D2, D3, and D4 receptors were measured in vitro. Binding studies were also conducted to determine if the compounds bound to sigma ...
Bioorganic & Medicinal Chemistry, 2006
A series of indole compounds have been prepared and evaluated for affinity at D2-like dopamine re... more A series of indole compounds have been prepared and evaluated for affinity at D2-like dopamine receptors using stably transfected HEK cells expressing human D2, D3, or D4 dopamine receptors. These compounds share structural elements with the classical D2-like dopamine receptor antagonists, haloperidol, N-methylspiperone, and benperidol. The compounds that share structural elements with N-methylspiperone and benperidol bind non-selectively to the D2
Journal of Medicinal Chemistry, 2011
A series of fluorine containing N-(2-methoxyphenyl)piperazine and N-(2-fluoroethoxy)piperazine an... more A series of fluorine containing N-(2-methoxyphenyl)piperazine and N-(2-fluoroethoxy)piperazine analogues were synthesized and their affinities for human dopamine D 2 , D 3 and D 4 receptors were determined. Radioligand binding studies identified five compounds, 18a, 20a, 20c, 20e and 21e, which bind with high affinity at D 3 (K i = 0.17 to 5 nM) and moderate to high selectivity for D 3 vs. D 2 receptors (ranging from ∼25 to 163-fold). These compounds were also evaluated for intrinsic activity at D 2 and D 3 receptors using a forskolin-dependent adenylyl cyclase assay. This panel of compounds exhibits varying receptor subtype binding selectivity and intrinsic activity at D 2 vs. D 3 receptors. These compounds may be useful for behavioral pharmacology studies on the role of D 2like dopamine receptors in neuropsychiatric and neurological disorders. Furthermore, compound 20e, which has the highest binding affinity and selectivity for the D 3 receptor (K i = 0.17 nM for D 3 , 163-fold selectivity for D 3 vs. D 2 receptors) represents a candidate fluorine-18 radiotracer for in vivo PET imaging studies on the regulation of D 3 receptor expression.
Bioorganic & Medicinal Chemistry, 2011
2-((4-(1-[11C]Methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-quinoline (MP-10), a specif... more 2-((4-(1-[11C]Methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-quinoline (MP-10), a specific PDE10A inhibitor (IC50=0.18nM with 100-fold selectivity over other PDEs), was radiosynthesized by alkylation of the desmethyl precursor with [11C]CH3I, ∼45% yield, >92% radiochemical purity, >370GBq/μmol specific activity at end of bombardment (EOB). Evaluation in Sprague–Dawley rats revealed that [11C]MP-10 had highest brain accumulation in the PDE10A enriched-striatum, the 30min striatum: cerebellum ratio reached 6.55. MicroPET studies
Bioorganic & medicinal …, 2005
A series of N-(2-methoxyphenyl) piperazine and N-(2, 3-dichlorophenyl) piperazine analogs were pr... more A series of N-(2-methoxyphenyl) piperazine and N-(2, 3-dichlorophenyl) piperazine analogs were prepared and their affinities for dopamine D2, D3, and D4 receptors were measured in vitro. Binding studies were also conducted to determine if the compounds bound to sigma ...
Bioorganic & Medicinal Chemistry, 2006
A series of indole compounds have been prepared and evaluated for affinity at D2-like dopamine re... more A series of indole compounds have been prepared and evaluated for affinity at D2-like dopamine receptors using stably transfected HEK cells expressing human D2, D3, or D4 dopamine receptors. These compounds share structural elements with the classical D2-like dopamine receptor antagonists, haloperidol, N-methylspiperone, and benperidol. The compounds that share structural elements with N-methylspiperone and benperidol bind non-selectively to the D2