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  • SAR and QSAR study on 2-aminothiazole derivatives, modulators of transcriptional repression in Huntington's disease.

SAR and QSAR study on 2-aminothiazole derivatives, modulators of transcriptional repression in Huntington's disease.

Bioorganic & medicinal chemistry (2008-04-15)
Samantha Leone, Cesare Mutti, Aleksey Kazantsev, Mattia Sturlese, Stefano Moro, Elena Cattaneo, Dorotea Rigamonti, Alessandro Contini
ABSTRACT

REST/NRSF is a multifunctional transcription factor that represses or silences many neuron-specific genes in both neural and non-neural cells by recruitment to its cognate RE1/NRSE regulatory sites. An increase in RE1/NRSE genomic binding is found in Huntington's disease (HD), resulting in the repression of REST/NRSF regulated gene transcription, among which BDNF, thus representing one of the possible detrimental effectors in HD. Three 2-aminothiazole derivatives were recently identified as potent modulators of the RE1/NRSE silencing activity through a cell-based gene reporter assay. In this study, the structure-activity relationships (SAR) of a library of commercially available 2-aminoisothiazoles diversely substituted at the amino group or at position 4 has been evaluated. A quantitative structure-activity relationship analysis performed using the Phase strategy yielded highly predictive 3D-QSAR pharmacophore model for in silico drug screening.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2-Aminothiazole, 97%