115703-22-5Relevant academic research and scientific papers
MACROCYCLIC SULFONYLAMIDE DERIVATIVES USEFUL AS NLRP3 INHIBITORS
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Page/Page column 164-165, (2021/02/26)
The present invention relates to macrocyclic compounds, such as macrocyclic sulfonyl amides. The present invention further relates to associated salts, solvates, prodrugs and pharmaceutical compositions, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by NLRP3 inhibition.
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
, 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.
