| Literature DB >> 27088900 |
Abbas M Walji1, Eric D Hostetler2, Harold Selnick1, Zhizhen Zeng2, Patricia Miller2, Idriss Bennacef2, Cristian Salinas2, Brett Connolly2, Liza Gantert2, Marie Holahan2, Stacey O'Malley2, Mona Purcell2, Kerry Riffel2, Jing Li3, Jaume Balsells3, Julie A OBrien4, Stacey Melquist4, Aileen Soriano5, Xiaoping Zhang5, Aimie Ogawa5, Serena Xu5, Elizabeth Joshi6, Joseph Della Rocca7, Fred J Hess8, Joel Schachter8, David Hesk9, David Schenk9, Arie Struyk10, Kerim Babaoglu11, Talakad G Lohith2, Yaode Wang12, Kun Yang12, Jianmin Fu12, Jeffrey L Evelhoch2, Paul J Coleman1.
Abstract
Neurofibrillary tangles (NFTs) made up of aggregated tau protein have been identified as the pathologic hallmark of several neurodegenerative diseases including Alzheimer's disease. In vivo detection of NFTs using PET imaging represents a unique opportunity to develop a pharmacodynamic tool to accelerate the discovery of new disease modifying therapeutics targeting tau pathology. Herein, we present the discovery of 6-(fluoro-(18)F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine, 6 ([(18)F]-MK-6240), as a novel PET tracer for detecting NFTs. 6 exhibits high specificity and selectivity for binding to NFTs, with suitable physicochemical properties and in vivo pharmacokinetics.Entities:
Mesh：
Substances：
Year: 2016 PMID： 27088900 DOI： 10.1021/acs.jmedchem.6b00166
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446