3598-08-1Relevant academic research and scientific papers
Structure-Activity Studies of Bis-O-Arylglycolamides: Inhibitors of the Integrated Stress Response
Hearn, Brian R.,Jaishankar, Priyadarshini,Sidrauski, Carmela,Tsai, Jordan C.,Vedantham, Punitha,Fontaine, Shaun D.,Walter, Peter,Renslo, Adam R.
, p. 870 - 880 (2016/05/02)
The integrated stress response comprises multiple signaling pathways for detecting and responding to cellular stress that converge at a single event - the phosphorylation of Ser51 on the α-subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α-P) results in attenuation of global protein synthesis via the inhibitory effects of eIF2α-P on eIF2B, the guanine exchange factor (GEF) for eIF2. Herein we describe structure-activity relationship (SAR) studies of bis-O-arylglycolamides, first-in-class integrated stress response inhibitors (ISRIB). ISRIB analogues make cells insensitive to the effects of eIF2α-P by activating the GEF activity of eIF2B and allowing global protein synthesis to proceed with residual unphosphorylated eIF2α. The SAR studies described herein support the proposed pharmacology of ISRIB analogues as binding across a symmetrical protein-protein interface formed between protein subunits of the dimeric eIF2B heteropentamer. Stress management: Herein we describe structure-activity studies of bis-O-arylglycolamides, first-in-class Integrated Stress Response InhiBitors (ISRIB). ISRIB analogues make cells insensitive to the effects of eIF2α phosphorylation by activating eIF2B, the guanine exchange factor for eIF2. ISRIB analogues are thought to bind and stabilize a protein-protein interface in the dimeric form of the eIF2B heteropentameric protein complex.
NOVEL AMIDE AND AMIDINE DERIVATIVES AND USES THEREOF
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Page/Page column 37, (2010/11/03)
The present invention relates to inhibitors of 11-β-hydroxysteroid dehydrogenase type 1 enzyme and their use in treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, central nervous system disorders, and diseases and conditions that are related to excessive glucocorticoids.
EFFECT OF REMOTE HETEROATOM SUBSTITUENTS ON STEREOCHEMISTRY IN 1,2 H MIGRATION TO DIVALENT CARBON. EVIDENCE FOR " NEGATIVE " HYPERCONJUGATION OF CARBENE LONE PAIR
Tomioka, Hideo,Hayashi, Norihiro,Inoue, Noboru,Izawa, Yasuji
, p. 1651 - 1654 (2007/10/02)
Aryloxymethylchlorocarbene generated by photolysis of the corresponding diazirine afforded α-aryloxy-β-chloroalkene.The thermodynamically less stable Z-products are the major isomers and its content becomes dominant as more electron-withdrawing groups are
