On June 19, 2020, Roberts, Brett L.; Ma, Zhi-Xiong; Gao, Ang; Leisten, Eric D.; Yin, Dan; Xu, Wei; Tang, Weiping published an article.Application In Synthesis of tert-Butyl 2-(2-(2-(tosyloxy)ethoxy)ethoxy)acetate The title of the article was Two-Stage Strategy for Development of Proteolysis Targeting Chimeras and its Application for Estrogen Receptor Degraders. And the article contained the following:
Proteolysis targeting chimeras (PROTACs) have emerged as useful chem. probes and potential therapeutics by taking advantage of the ubiquitin-proteasome system to degrade intracellular disease-associated proteins. PROTACs are heterobifunctional mols. composed of a target protein ligand, E3 ubiquitin ligase ligand, and a linker between them. The generation of efficient PROTACs requires screening of many parameters, especially the lengths and types of the linkers. The authors report the proof-of-concept study using a two-stage strategy to facilitate the development of PROTACs against the estrogen receptor (ER). In stage one, a library of close to 100 PROTACs was synthesized by simply mixing a library of ERα ligands containing a hydrazide functional group at different positions with a preassembled library of E3 ligase ligands bearing different types and lengths of linkers with a terminal aldehyde group in a 1:1 ratio. Cell-based screening occurred without further purification, because the formation of the acylhydrazone linkage is highly efficient and produces water as the only byproduct. Compound A3 was the most potent ER degrader in two ER+ cell lines (DC50= ~10 nM, Dmax= â?95%). Stage two involved transformation to a more stable amide linker to generate a more drug-like mol. The new compound, AM-A3, showed comparable biol. activity (DC50 = 1.1 nM, Dmax = 98%) and induced potent antiproliferation (IC50= 13.2 nM, Imax= 69%) in MCF-7. This proof-of -concept study demonstrates that the two-stage strategy can significantly facilitate the development of PROTACs against ER without the tedious process of making large numbers of PROTACs one by one. It has the potential to be expanded to many other targets. The experimental process involved the reaction of tert-Butyl 2-(2-(2-(tosyloxy)ethoxy)ethoxy)acetate(cas: 882518-89-0).Application In Synthesis of tert-Butyl 2-(2-(2-(tosyloxy)ethoxy)ethoxy)acetate
The Article related to proteolysis targeting chimera estrogen receptor degrader, Pharmacology: Structure-Activity and other aspects.Application In Synthesis of tert-Butyl 2-(2-(2-(tosyloxy)ethoxy)ethoxy)acetate
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics