227095-00-3Relevant academic research and scientific papers
Discovery and Development of Small-Molecule Inhibitors of Glycogen Synthase
Tang, Buyun,Frasinyuk, Mykhaylo S.,Chikwana, Vimbai M.,Mahalingan, Krishna K.,Morgan, Cynthia A.,Segvich, Dyann M.,Bondarenko, Svitlana P.,Mrug, Galyna P.,Wyrebek, Przemyslaw,Watt, David S.,Depaoli-Roach, Anna A.,Roach, Peter J.,Hurley, Thomas D.
, p. 3538 - 3551 (2020/04/30)
The overaccumulation of glycogen appears as a hallmark in various glycogen storage diseases (GSDs), including Pompe, Cori, Andersen, and Lafora disease. Accumulating evidence suggests that suppression of glycogen accumulation represents a potential therapeutic approach for treating these GSDs. Using a fluorescence polarization assay designed to screen for inhibitors of the key glycogen synthetic enzyme, glycogen synthase (GS), we identified a substituted imidazole, (rac)-2-methoxy-4-(1-(2-(1-methylpyrrolidin-2-yl)ethyl)-4-phenyl-1H-imidazol-5-yl)phenol (H23), as a first-in-class inhibitor for yeast GS 2 (yGsy2p). Data from X-ray crystallography at 2.85 ?, as well as kinetic data, revealed that H23 bound within the uridine diphosphate glucose binding pocket of yGsy2p. The high conservation of residues between human and yeast GS in direct contact with H23 informed the development of around 500 H23 analogs. These analogs produced a structure-activity relationship profile that led to the identification of a substituted pyrazole, 4-(4-(4-hydroxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)pyrogallol, with a 300-fold improved potency against human GS. These substituted pyrazoles possess a promising scaffold for drug development efforts targeting GS activity in GSDs associated with excess glycogen accumulation.
COMPOUNDS FOR IMMUNOPOTENTIATION
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Page/Page column 113, (2010/02/15)
Methods of stimulating an immune response and treating patients responsive thereto with 3,4-di(1H-indol-3-yl)-1H-pyrrole-2,5-diones, staurosporine analogs, derivatized pyridazines, chromen-4-ones, indolinones, quinazolines, nucleoside analogs, and other small molecules are disclosed.
Synthetic analogs of xanthocercin
Otsalyuk,Tkachuk,Bondarenko,Chkhalo,Khilya
, p. 284 - 288 (2007/10/03)
Synthetic analogs of xanthocercin in the molecules of which benzodioxole, benzodioxane, or benzodioxepane fragments are annellated to a γ-pyrone ring have been obtained. The structures of the new compounds have been confirmed by analytical and spectral re
