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Anilinotriazoles as potent gamma secretase modulators
Institution:1. Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium;2. Discovery Sciences, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium;3. Neuroscience, Janssen Research & Development, Jarama 75, 45007 Toledo, Spain;1. Platov South-Russian State Polytechnic University (NPI), Prosveschenya 132, 346428 Novocherkassk, Russia;2. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow 119991, Russia;3. M.V. Lomonosov Moscow State University, Leninskie Gory 1-3, Moscow 119991, Russia;4. A.N. Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Leninsky Prospect 31, Moscow 119071, Russia;1. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;2. Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;1. Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan;2. Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan;3. Molecular Chirality Research Center, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract:The design and synthesis of a novel series of potent gamma secretase modulators is described. Exploration of various spacer groups between the triazole ring and the aromatic appendix in 2 has led to anilinotriazole 28, which combined high in vitro and in vivo potency with an acceptable drug-like profile.
Keywords:Gamma secretase modulators  Alzheimer’s disease  Anilinotriazoles
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