582-77-4Relevant articles and documents
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Kubiczek
, p. 100,102 (1943)
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Dihydroquinazolines enhance 20S proteasome activity and induce degradation of α-synuclein, an intrinsically disordered protein associated with neurodegeneration
Campbell, Molly V.,Davies, Steven B.,Fiolek, Taylor J.,Magyar, Christina L.,Mosey, R. Adam,Savich, Christopher J.,Tepe, Jetze J.,Wall, Tyler J.
supporting information, (2021/02/06)
Aggregates or oligomeric forms of many intrinsically disordered proteins (IDPs), including α-synuclein, are hallmarks of neurodegenerative diseases, like Parkinson's and Alzheimer's disease, and key contributors to their pathogenesis. Due to their disordered nature and therefore lack of defined drug-binding pockets, IDPs are difficult targets for traditional small molecule drug design and are often referred to as “undruggable”. The 20S proteasome is the main protease that targets IDPs for degradation and therefore small molecule 20S proteasome enhancement presents a novel therapeutic strategy by which these undruggable IDPs could be targeted. The concept of 20S activation is still relatively new, with few potent activators having been identified thus far. Herein, we synthesized and evaluated a library of dihydroquinazoline analogues and discovered several promising new 20S proteasome activators. Further testing of top hits revealed that they can enhance 20S mediated degradation of α-synuclein, the IDP associated with Parkinson's disease.
Chromium-catalyzed ligand-free amidation of esters with anilines
Chen, Changpeng,Ling, Liang,Luo, Meiming,Zeng, Xiaoming
supporting information, p. 762 - 766 (2021/04/14)
Amides are important structural motifs in pharmaceutical and agrochemical chemistry because of the intriguing biological active properties. We report here the amidation of commercially available esters with anilines that was promoted by low-cost and air-stable chromium(III) pre-catalyst combined with magnesium, providing access to amides. This reaction occurs without the use of external ligands in a simple operation. Mechanistic studies indicate that a reactive aminated Cr species responsible for the amidation can be considered, which may be formed by reaction of low-valent Cr with aniline followed by reduction with hydrogen evolution.
