Investigation of an F-labelled Imidazopyridotriazine for Molecular Imaging of Cyclic Nucleotide Phosphodiesterase 2A.

Specific radioligands for in vivo visualization and quantification of cyclic nucleotide phosphodiesterase 2A (PDE2A) by positron emission tomography (PET) are increasingly gaining interest in brain research. Herein we describe the synthesis, the F-labelling as well as the biological evaluation of our latest PDE2A (radio-)ligand 9-(5-Butoxy-2-fluorophenyl)-2-(2-([F])fluoroethoxy)-7-methylimidazo[5,1-]pyrido[2,3-][1,2,4]triazine (([F])). It is the most potent PDE2A ligand out of our series of imidazopyridotriazine-based derivatives so far (IC hPDE2A = 3.

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

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).

Development of highly potent phosphodiesterase 10A (PDE10A) inhibitors: Synthesis and in vitro evaluation of 1,8-dipyridinyl- and 1-pyridinyl-substituted imidazo[1,5-a]quinoxalines.

Herein we report the synthesis of fluorinated inhibitors of phosphodiesterase 10A (PDE10A) which can be used potentially as lead structure for the development of a (18)F-labeled PDE10A imaging agent for positron emission tomography. The use of ortho-fluoropyridines as residues could potentially enable the introduction of (18)F through nucleophilic substitution for radiolabeling purposes. 2-Fluoropyridines are introduced by a Suzuki coupling at different positions of the molecule.

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

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.

Large-scale mining for similar protein binding pockets: with RAPMAD retrieval on the fly becomes real.

Determination of structural similarities between protein binding pockets is an important challenge in in silico drug design. It can help to understand selectivity considerations, predict unexpected ligand cross-reactivity, and support the putative annotation of function to orphan proteins. To this end, Cavbase was developed as a tool for the automated detection, storage, and classification of putative protein binding sites.