158351-87-2Relevant articles and documents
Fused 3-hydroxy-3-trifluoromethylpyrazoles inhibit mutant huntingtin toxicity
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
supporting information, p. 979 - 984 (2013/10/22)
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 identification of compound 4f, which demonstrated to be active in a Htt171-82Q rat primary striatal neuron assay and a PC12-Exon-1 based assay. This compound was selected for testing in R6/2 mice, in which it was well-tolerated and showed a positive effect on body weight and a positive trend in preventing ventricular volume enlargment. These studies provide strong rationale for further testing the potential benefits of 3-hydroxy-3-trifluoromethylpyrazoles in treating HD.
COMPOUNDS WHICH POTENTIATE AMPA RECEPTOR AND USES THEREOF IN MEDICINE
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Page/Page column 16, (2010/06/16)
Compounds of formula (I), and salts and solvates thereof are provided: Processes for preparation, pharmaceutical compositions, and uses thereof as a medicament, for example in the treatment of a disease or condition mediated by a reduction or imbalance in glutamate receptor function, such as schizophrenia or cognition impairment, are also disclosed.
COMPOUNDS WHICH POTENTIATE AMPA RECEPTOR AND USES THEREOF IN MEDICINE
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Page/Page column 37-38, (2008/12/07)
Compound of formula (I) and salts thereof are provided: wherein A, R1, R, R2 are as defined in the specification. Processes for preparation, pharmaceutical compositions, and uses thereof as a medicament, for example in the treatment of a disease or condition mediated by a reduction or imbalance in glutamate receptor function, such as schizophrenia or cognition impairment, are also disclosed.