Fused 3-hydroxy-3-trifluoromethylpyrazoles inhibit mutant huntingtin toxicity

…, R Luthi-Carter, L Magnoni, V Miragliotta…

Index: La Rosa, Salvatore; Benicchi, Tiziana; Bettinetti, Laura; Ceccarelli, Ilaria; Diodato, Enrica; Federico, Cesare; Fiengo, Pasquale; Franceschini, Davide; Gokce, Ozgun; Heitz, Freddy; Lazzeroni, Giulia; Luthi-Carter, Ruth; Magnoni, Letizia; Miragliotta, Vincenzo; Scali, Carla; Valacchi, Michela ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 10 p. 979 - 984

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Citation Number: 4

Abstract

Here, we describe the selection and optimization of a chemical series active in both a full- length and a fragment-based Huntington's disease (HD) assay. Twenty-four thousand small molecules were screened in a phenotypic HD assay, identifying a series of compounds bearing a 3-hydroxy-3-trifluoromethylpyrazole moiety as able to revert the toxicity induced by full-length mutant Htt by up to 50%. A chemical exploration around the series led to the ...