La Rosa, Salvatore published the artcileFused 3-Hydroxy-3-trifluoromethylpyrazoles Inhibit Mutant Huntingtin Toxicity, Quality Control of 637336-53-9, the main research area is hydroxytrifluoromethylpyrazole preparation SAR Huntingtons disease; 3-hydroxy-3-trifluoromethylpyrazoles; ADME; Huntington’s disease; R6/2 mouse model; mutant Htt toxicity; phenotypic screening.
Here, we describe the selection and optimization of a chem. series active in both a full-length and a fragment-based Huntington’s disease (HD) assay. Twenty-four thousand small mols. 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 chem. exploration around the series led to the identification of compound (I), 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 pos. effect on body weight and a pos. trend in preventing ventricular volume enlargement. These studies provide strong rationale for further testing the potential benefits of 3-hydroxy-3-trifluoromethylpyrazoles in treating HD.
ACS Medicinal Chemistry Letters published new progress about Huntington disease. 637336-53-9 belongs to class pyrazoles-derivatives, name is Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, and the molecular formula is C6H9N3O2, Quality Control of 637336-53-9.
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics