- Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer's Disease with Positron Emission Tomography
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Aggregates of tau and beta amyloid (Aβ) plaques constitute the histopathological hallmarks of Alzheimer's disease and are prominent targets for novel therapeutics as well as for biomarkers for diagnostic in vivo imaging. In recent years much attention has been devoted to the discovery and development of new PET tracers to image tau aggregates in the living human brain. Access to a selective PET tracer to image and quantify tau aggregates represents a unique tool to support the development of any novel therapeutic agent targeting pathological forms of tau. The objective of the study described herein was to identify such a novel radiotracer. As a result of this work, we discovered three novel PET tracers (2-(4-[11C]methoxyphenyl)imidazo[1,2-a]pyridin-7-amine 7 ([11C]RO6924963), N-[11C]methyl-2-(3-methylphenyl)imidazo[1,2-a]pyrimidin-7-amine 8 ([11C]RO6931643), and [18F]2-(6-fluoropyridin-3-yl)pyrrolo[2,3-b:4,5-c′]dipyridine 9 ([18F]RO6958948)) with high affinity for tau neurofibrillary tangles, excellent selectivity against Aβ plaques, and appropriate pharmacokinetic and metabolic properties in mice and non-human primates.
- Gobbi, Luca C.,Knust, Henner,K?rner, Matthias,Honer, Michael,Czech, Christian,Belli, Sara,Muri, Dieter,Edelmann, Martin R.,Hartung, Thomas,Erbsmehl, Isabella,Grall-Ulsemer, Sandra,Koblet, Andreas,Rueher, Marianne,Steiner, Sandra,Ravert, Hayden T.,Mathews, William B.,Holt, Daniel P.,Kuwabara, Hiroto,Valentine, Heather,Dannals, Robert F.,Wong, Dean F.,Borroni, Edilio
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p. 7350 - 7370
(2017/09/22)
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- IMIDAZOPYRIMIDINE DERIVATIVES
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The invention is concerned with novel imidazopyrimidine derivatives of formula (I) wherein R1, R2 and R8 are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit PDE10A and can be used as pharmaceuticals.
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Page/Page column 19
(2011/10/12)
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- N-(IMIDAZOPYRIMIDIN-7-YL)-HETEROARYLAMIDE DERIVATIVES AND THEIR USE AS PDE10A INHIBITORS
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The invention is concerned with novel imidazopyrimidine derivatives of formula (I) wherein R1, R2 and R8 are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit PDEIOA and used as medicaments.
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Page/Page column 56
(2011/10/13)
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