1015460-62-4Relevant articles and documents
PI-2620 Lead Optimization Highlights the Importance of Off-Target Assays to Develop a PET Tracer for the Detection of Pathological Aggregated Tau in Alzheimer's Disease and Other Tauopathies
Berndt, Mathias,Capotosti, Francesca,Dinkelborg, Ludger,Gabellieri, Emanuele,Hickman, David,Kroth, Heiko,Molette, Jerome,Mueller, Andre,Oden, Felix,Pfeifer, Andrea,Schieferstein, Hanno,Schmitt-Willich, Heribert,Serra, Andreia Monica,Sreenivasachary, Nampally,Stephens, Andrew
, p. 12808 - 12830 (2021/09/13)
The first candidate PI-2014 was tested in healthy controls and subjects with Alzheimer's disease (AD). As PI-2014 displayed off-target binding to monoamine oxidase A (MAO-A), a new lead with improved binding to Tau and decreased MAO-A binding was required. For compound optimization, Tau binding assays based on both human AD brain homogenate and Tau-paired helical filaments were employed. Furthermore, two MAO-A screening assays based on (1) human-recombinant MAO-A and (2) displacement of 2-fluoro-ethyl-harmine from mouse brain homogenate were employed. Removing the N-methyl group from the tricyclic core resulted in compounds displaying improved Tau binding. For the final round of optimization, the cyclic amine substituents were replaced by pyridine derivatives. PI-2620 (2-(2-fluoropyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine) emerged as a best candidate displaying high Tau binding, low MAO-A binding, high brain uptake, and fast and complete brain washout. Furthermore, PI-2620 showed Tau binding on brain sections from corticobasal degeneration, progressive supranuclear palsy, and Pick's disease.
GAMMA-CARBOLINE COMPOUNDS FOR THE DETECTION OF TAU AGGREGATES
-
Page/Page column 27, (2019/08/12)
The present invention relates to novel compounds of the formula (II) and formula (III) that can be employed in the selective Tau detection of disorders and abnormalities associated with Tau aggregates such as Alzheimer's disease and other tauopathies using Positron Emission Tomography (PET) Imaging.
Organic light-emitting device
-
Paragraph 0384; 0385; 0395-0398, (2019/06/04)
The present invention relates to an organic light emitting device having excellent electrical properties and thermal stability, which comprises: a first electrode; a second electrode; and an organic layer disposed between the first and second electrodes,
Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer's Disease with Positron Emission Tomography
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
, p. 7350 - 7370 (2017/09/22)
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.
Microwave-enhanced Fischer reaction: An efficient one-pot synthesis of γ-carbolines
Chen, Jing,Chen, Weiliang,Hu, Yongzhou
, p. 77 - 82 (2008/09/21)
γ-Carbolines were obtained in a simple one-pot Fischer reaction starting from N-acetyl-3-bromo-4-piperidone hydrobromide and substituted arylhydrazine hydrochlorides in acidic media under microwave irradiation or by a thermal process. The optimization procedures are reported in detail, and the results from microwave processes are compared with conventional ones. Georg Thieme Verlag Stuttgart.
