کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1360925 | 981452 | 2008 | 9 صفحه PDF | دانلود رایگان |
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.
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Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 10, 15 May 2008, Pages 5695–5703