57335-98-5Relevant articles and documents
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.
, (2021)
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.
COMPOUND, CURED PRODUCT, POLYMER, PHOTO-ALIGNMENT FILM, OPTICALLY ANISOTROPIC BODY AND LIQUID CRYSTAL DISPLAY ELEMENT
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Paragraph 0187, (2018/08/30)
A compound and a polymer which can each form a photo-alignment film having excellent ability of controlling alignment, a photo-alignment film obtained using the polymer and an optically anisotropic body and a liquid crystal display element each having the photo-alignment film are provided. A compound represented by the general formula (1). In the formula, P represents a polymerizable group, Z and Z1 represent divalent linking groups, A and A1 represent divalent cyclic groups, and X1 to X5 each independently represent a hydrogen atom, a fluorine atom, a chlorine atom, a hydroxy group, a nitro group, a cyano group or an alkyl group having 1 to 40 carbon atoms which may have a substituent, provided that X1, X2, X4 and X5 are not simultaneously hydrogen atoms.
Synthesis, antiproliferative activity evaluation and structure-activity relationships of novel aromatic urea and amide analogues of N-phenyl-N′- (2-chloroethyl)ureas
Fortin, Sébastien,Moreau, Emmanuel,Lacroix, Jacques,C?té, Marie-France,Petitclerc, éric,C.-Gaudreault, René
body text, p. 2928 - 2937 (2010/08/20)
Seven subsets of aromatic urea and amide analogues of N-phenyl-N′-(2- chloroethyl)ureas (CEU) have been synthesized by nucleophilic addition of 3-chloropropylisocyanate, 2-chloroacetylisocyanate, ethylisocyanate, 2-chloroacetyl chloride, 3-chloropropanoyl
