Select 3′,5′-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain

Kelly, Michy P.; Adamowicz, Wendy O.; Bove, Susan E.; Hartman, Alexander; Mariga, Abigail; Pathak, Geetanjali; Reinhart, Veronica; Romegialli, Alison; Kleiman, Robin J.

doi:10.1016/j.cellsig.2013.10.007

Cited by 129 publications

(196 citation statements)

References 117 publications

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“…This procedure was repeated twice with the filtrate and the dry precipitates were combined to afford 4.54 g (79%) of 2. [5,1-c]pyrido [2,3-e] [1,2,4]triazine (3) [38]. Under ice bath cooling, compound 2 (100 mg, 1 eq.)…”

Section: Synthesesmentioning

confidence: 99%

“…Furthermore, the patent does not provide NMR data of the published compounds 1-4 or TA1, which are reported herein. (1) [38]. To 4.02 g (1.6 eq.)…”

Section: Synthesesmentioning

confidence: 99%

“…Evaporation of the solvent and subsequent purification by column chromatography (EtOAc/ n-hexane, 1:2, v/v) afforded 1 as a yellow solid (6.65 g, 93%). 1 (2) [38]. Compound 1 (6.62 g, 1 eq.)…”

Section: Synthesesmentioning

confidence: 99%

“…The PDE family subtypes differ in their three-dimensional structure, kinetic and regulatory properties, cellular expression, intracellular location, inhibitor sensitivities, substrate selectivity and distribution within the organism. Due to hydrolysis of the cyclic nucleotides, PDEs affect the second messenger signaling cascades of cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) [1,2]. Therefore, pharmacological inhibition of PDEs has the potential to enhance cyclic nucleotide signaling and can provide a strategy for the prevention or treatment of various diseases [2,[5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…Phosphodiesterases (PDEs) are a class of intracellular enzymes consisting of 11 families and 21 isoforms [1][2][3][4]. The PDE family subtypes differ in their three-dimensional structure, kinetic and regulatory properties, cellular expression, intracellular location, inhibitor sensitivities, substrate selectivity and distribution within the organism.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Synthesis, 18F-Radiolabelling and Biological Characterization of Novel Fluoroalkylated Triazine Derivatives for in Vivo Imaging of Phosphodiesterase 2A in Brain via Positron Emission Tomography

et al. 2015

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Phosphodiesterase 2A (PDE2A) is highly and specifically expressed in particular brain regions that are affected by neurological disorders and in certain tumors. Development of a specific PDE2A radioligand would enable molecular imaging of the PDE2A protein via positron emission tomography (PET). Herein we report on the syntheses of three novel fluoroalkylated triazine derivatives (TA2-4) and on the evaluation of their effect on the enzymatic activity of human PDE2A.

show abstract

Section: Synthesesmentioning

confidence: 99%

“…Furthermore, the patent does not provide NMR data of the published compounds 1-4 or TA1, which are reported herein. (1) [38]. To 4.02 g (1.6 eq.)…”

Section: Synthesesmentioning

confidence: 99%

Section: Synthesesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Synthesis, 18F-Radiolabelling and Biological Characterization of Novel Fluoroalkylated Triazine Derivatives for in Vivo Imaging of Phosphodiesterase 2A in Brain via Positron Emission Tomography

et al. 2015

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Phosphodiesterases and Cyclic Nucleotide Signaling In The CNS

Conti

Richter

2014

Cyclic‐Nucleotide Phosphodiesterases in the Central Nervous System

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Radiosynthesis and biological evaluation of the new PDE10A radioligand [¹⁸F]AQ28A

Wagner

Teodoro

Deuther‐Conrad

et al. 2016

Labelled Comp Radiopharmac

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Cyclic nucleotide phosphodiesterase 10A (PDE10A) regulates the level of the second messengers cAMP and cGMP in particular in brain regions assumed to be associated with neurodegenerative and psychiatric diseases. A better understanding of the pathophysiological role of the expression of PDE10A could be obtained by quantitative imaging of the enzyme by positron emission tomography (PET). Thus, in this study we developed, radiolabeled, and evaluated a new PDE10A radioligand, 8-bromo-1-(6-[ F]fluoropyridin-3-yl)-3,4-dimethylimidazo[1,5-a]quinoxaline ([ F]AQ28A). [ F]AQ28A was radiolabeled by both nucleophilic bromo-to-fluoro or nitro-to-fluoro exchange using K[ F]F-K -carbonate complex with different yields. Using the superior nitro precursor, we developed an automated synthesis on a Tracerlab FX F-N module and obtained [ F]AQ28A with high radiochemical yields (33 ± 6%) and specific activities (96-145 GBq·μmol ) for further evaluation. Initially, we investigated the binding of [ F]AQ28A to the brain of different species by autoradiography and observed the highest density of binding sites in striatum, the brain region with the highest PDE10A expression. Subsequent dynamic PET studies in mice revealed a region-specific accumulation of [ F]AQ28A in this region, which could be blocked by preinjection of the selective PDE10A ligand MP-10. In conclusion, the data suggest [ F]AQ28A is a suitable candidate for imaging of PDE10A in rodent brain by PET.

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Select 3′,5′-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain

Cited by 129 publications

References 117 publications

Synthesis, 18F-Radiolabelling and Biological Characterization of Novel Fluoroalkylated Triazine Derivatives for in Vivo Imaging of Phosphodiesterase 2A in Brain via Positron Emission Tomography

Synthesis, 18F-Radiolabelling and Biological Characterization of Novel Fluoroalkylated Triazine Derivatives for in Vivo Imaging of Phosphodiesterase 2A in Brain via Positron Emission Tomography

Phosphodiesterases and Cyclic Nucleotide Signaling In The CNS

Radiosynthesis and biological evaluation of the new PDE10A radioligand [¹⁸F]AQ28A

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Select 3′,5′-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain

Cited by 129 publications

References 117 publications

Synthesis, 18F-Radiolabelling and Biological Characterization of Novel Fluoroalkylated Triazine Derivatives for in Vivo Imaging of Phosphodiesterase 2A in Brain via Positron Emission Tomography

Synthesis, 18F-Radiolabelling and Biological Characterization of Novel Fluoroalkylated Triazine Derivatives for in Vivo Imaging of Phosphodiesterase 2A in Brain via Positron Emission Tomography

Phosphodiesterases and Cyclic Nucleotide Signaling In The CNS

Radiosynthesis and biological evaluation of the new PDE10A radioligand [18F]AQ28A

Contact Info

Product

Resources

About

Radiosynthesis and biological evaluation of the new PDE10A radioligand [¹⁸F]AQ28A