Synthetic Route of C3H8ClNOIn 2020 ,《Design, optimization, and study of small molecules that target tau pre-mRNA and affect splicing》 was published in Journal of the American Chemical Society. The article was written by Chen, Jonathan L.; Zhang, Peiyuan; Abe, Masahito; Aikawa, Haruo; Zhang, Liying; Frank, Alexander J.; Zembryski, Timothy; Hubbs, Christopher; Park, Ha Jeung; Withka, Jane; Steppan, Claire; Rogers, Lucy; Cabral, Shawn; Pettersson, Martin; Wager, Travis T.; Fountain, Matthew A.; Rumbaugh, Gavin; Childs-Disney, Jessica L.; Disney, Matthew D.. The article contains the following contents:
Approx. 95% of human genes are alternatively spliced, and aberrant splicing events can cause disease. One pre-mRNA that is alternatively spliced and linked to neurodegenerative diseases is tau (microtubule-associated protein tau), which can cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and can contribute to Alzheimer′s disease. Here, we describe the design of structure-specific lead small mols. that directly target tau pre-mRNA from sequence. This was followed by hit expansion and analog synthesis to further improve upon these initial lead mols. The emergent compounds were assessed for functional activity in a battery of assays, including binding assays and an assay that mimics mol. recognition of tau pre-mRNA by a U1 small nuclear ribonucleoprotein (snRNP) splicing factor. Compounds that emerged from these studies had enhanced potency and selectivity for the target RNA relative to the initial hits, while also having significantly improved drug-like properties. The compounds are shown to directly target tau pre-mRNA in cells, via chem. crosslinking and isolation by pull-down target profiling, and to rescue disease-relevant splicing of tau pre-mRNA in a variety of cellular systems, including primary neurons. More broadly, this study shows that lead, structure-specific compounds can be designed from sequence and then further optimized for their physicochem. properties while at the same time enhancing their activity. The results came from multiple reactions, including the reaction of Azetidin-3-ol hydrochloride(cas: 18621-18-6Synthetic Route of C3H8ClNO)
Azetidin-3-ol hydrochloride(cas:18621-18-6) is one of azetidine.Azetidines (azacyclobutanes) constitute a well-known class of heterocyclic compounds. Azetidine scaffold has been discovered in several natural products.Synthetic Route of C3H8ClNO Several pharmacologically important synthetic compounds also contain azetidine ring. Because of inherent ring strain, the synthesis of azetidines is a challenging endeavor.
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