Synthesis and biological evaluation of substituted [18F]Imidazo[1,2-a]pyridines and [18F]Pyrazolo[1,5-a]pyrimidines for the study of the peripheral benzodiazepine receptor using positron emission tomography

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dc.contributor.authorFookes, CJRen_AU
dc.contributor.authorPham, TQen_AU
dc.contributor.authorMattner, Fen_AU
dc.contributor.authorGreguric, Ien_AU
dc.contributor.authorLoc'h, Cen_AU
dc.contributor.authorLiu, Xen_AU
dc.contributor.authorBerghofer, PJen_AU
dc.contributor.authorShepherd, Ren_AU
dc.contributor.authorGrégoire, MCen_AU
dc.contributor.authorKatsifis, Aen_AU
dc.date.accessioned2020-03-24T02:54:36Zen_AU
dc.date.available2020-03-24T02:54:36Zen_AU
dc.date.issued2008-06-17en_AU
dc.date.statistics2020-03-20en_AU
dc.description.abstractThe fluoroethoxy and fluoropropoxy substituted 2-(6-chloro-2-phenyl)imidazo[1,2- a]pyridin-3-yl)- N, N-diethylacetamides 8 (PBR102) and 12 (PBR111) and 2-phenyl-5,7-dimethylpyrazolo[1,5- a]pyrimidin-3-yl)- N, N-diethylacetamides 15 (PBR099) and 18 (PBR146) were synthesized and found to have high in vitro affinity and selectivity for the peripheral benzodiazepine receptors (PBRs) when compared with the central benzodiazepine receptors (CBRs). The corresponding radiolabeled compounds [ (18)F] 8 [ (18)F] 12, [ (18)F] 15, and [ (18)F] 18 were prepared from their p-toluenesulfonyl precursors in 50-85% radiochemical yield. In biodistribution studies in rats, the distribution of radioactivity of the [ (18)F]PBR compounds paralleled the known localization of PBRs. In the olfactory bulbs, where the uptake of radioactivity was higher than in the rest of the brain, PK11195 and Ro 5-4864 were able to significantly inhibit [ (18)F] 12, while little or no pharmacological action of these established PBR drugs were observed on the uptake of [ (18)F] 8, [ (18)F] 15, and [ (18)F] 18 compared to control animals. Hence, [ (18)F] 12 appeared to be the best candidate for evaluation as an imaging agent for PBR expression in neurodegenerative disorders. © 2008 American Chemical Societyen_AU
dc.identifier.citationFookes, C. J., Pham, T. Q., Mattner, F., Greguric, I., Loc’h, C., Liu, X., Berghofer, P., Shepherd, R., Grégoire, M. C. & Katsifis, A. (2008). Synthesis and biological evaluation of substituted [18F] imidazo [1, 2-a] pyridines and [18F] pyrazolo [1, 5-a] pyrimidines for the study of the peripheral benzodiazepine receptor using positron emission tomography. Journal of Medicinal Chemistry, 51(13), 3700-3712. doi:10.1021/jm7014556en_AU
dc.identifier.govdoc8749en_AU
dc.identifier.issn1520-4804en_AU
dc.identifier.issue13en_AU
dc.identifier.journaltitleJournal of Medicinal Chemistryen_AU
dc.identifier.pagination3700-3712en_AU
dc.identifier.urihttps://doi.org/10.1021/jm7014556en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/9216en_AU
dc.identifier.volume51en_AU
dc.language.isoenen_AU
dc.publisherAmerican Chemical Societyen_AU
dc.subjectSynthesisen_AU
dc.subjectImidazolesen_AU
dc.subjectPurinesen_AU
dc.subjectPyrazolesen_AU
dc.subjectReceptorsen_AU
dc.subjectPositron computed tomographyen_AU
dc.titleSynthesis and biological evaluation of substituted [18F]Imidazo[1,2-a]pyridines and [18F]Pyrazolo[1,5-a]pyrimidines for the study of the peripheral benzodiazepine receptor using positron emission tomographyen_AU
dc.typeJournal Articleen_AU
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