52449-77-1Relevant articles and documents
Bi-aryl analogues of salicylic acids: Design, synthesis and sar study to ameliorate endoplasmic reticulum stress
Kim, Ye Eun,Kim, Dong Hwan,Choi, Ami,Jang, Seoul,Jeong, Kwiwan,Kim, Young-Mi,Nam, Tae-Gyu
, p. 3593 - 3604 (2021/08/30)
Introduction: Endoplasmic reticulum (ER) stress condition is characterized as the accu-mulation of misfolded or unfolded proteins in lumen of ER. This condition has been implicated in various diseases and pathologies including β-cell apoptosis, Alzheimer’s disease and atherosclerosis. We have reported that hydroxynaphthoic acids (HNA), naphtha-lene analogues of salicylic acid (SA), reduced ER stress. In this study, we explored structural modification to bi-aryl analogues of SA. Methods: Palladium-catalyzed cross-coupling was applied to synthesize bi-aryl analogues of SA. Anti-ER stress activity was monitored by using our cell-based assay system where ER stress is induced by tunicamycin. To monitor ER stress markers, ER stress was induced physiologically relevant palmitate system. Results: Many analogues decreased ER stress signal induced by tunicamycin. Compounds creating dihedral angle between Ar group and SA moiety generally increased the activity but gave some cytotoxicity to indicate the crucial role of flat conformation of aromatic region. The best compound (16e) showed up to almost 6-fold and 90-fold better activity than 3-HNA and tauro-ursodeoxycholic acid, positive controls, respectively. ER stress markers such as p-PERK and p-JNK were accordingly decreased in Western blotting upon treatment of 16e under palmitate-induced condition. Conclusion: Anti-ER stress activity and toxicity profile of bi-aryl analogues of SA could provide a novel platform for potential therapy for protein misfolding diseases.
Acid-catalyzed dehydration of naphthalene-cis-1,2-dihydrodiols: Origin of impaired resonance effect of 3-substituents
Kudavalli, Jaya Satyanarayana,Boyd, Derek R.,Sharma, Narain D.,More O'Ferrall, Rory A.
supporting information; experimental part, p. 9338 - 9343 (2012/01/03)
Acid-catalyzed dehydrations of substituted naphthalene-cis-1,2-dihydrodiols occur with loss of the 1- or 2-OH group to form 2- and 1-naphthols, respectively. Effects of substituents MeO, Me, H, F, Br, I, and CN at 3-, 6-, and 7-positions of the naphthalene ring are consistent with rate-determining formation of β-hydroxynaphthalenium ion (carbocation) intermediates. For reaction of the 1-hydroxyl group the 3-substituents are correlated by the Yukawa-Tsuno relationship with ρ = -4.7 and r = 0.25 or by σp constants with ρ = -4.25; for reaction of the 2-hydroxyl group the 3-substituents are correlated by σm constants with ρ = -8.1. The correlations for the 1-hydroxyl imply a surprisingly weak resonance interaction of +M substituents (MeO, Me) with a carbocation reaction center but are consistent with the corresponding correlation for acid-catalyzed dehydration of 3-substituted benzene-cis-1,2-dihydrodiols for which ρ = -6.9 and r = 0.43. Substituents at the 6- and 7-positions of the naphthalene rings by contrast are correlated by σ+ with ρ = -3.2 for reaction of the 1-hydroxyl group and ρ = -2.7 for reaction of the 2-hydroxyl group. The unimpaired resonance implied by these substituent effects appears to be inconsistent with a previous explanation of the weak resonance of the 3-substituents in terms of imbalance of charge development and/or nonplanarity of the benzenium ring in the transition state. An alternative possibility is that the adjacent hydroxyl group interferes sterically with conjugation of +M substituents. "Hyperaromaticity" of the arenium ion intermediates does not appear to be a factor influencing this behavior.
Thiazoline acid derivatives
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, (2008/06/13)
Thiazoline acids and derivatives useful as chelators of trivalent metals in therapeutic applications have been prepared.
Synthesis and biological evaluation of naphthyldesferrithiocin iron chelators
Bergeron, Raymond J.,Wiegand, Jan,Wollenweber, Markus,McManis, James S.,Algee, Samuel E.,Ratliff-Thompson, Katie
, p. 1575 - 1581 (2007/10/03)
The synthesis and iron-clearing properties of the naphthyldesferrithiocins 2-(2'-hydroxynaphth-1'-yl)-Δ2-thiazoline-(4R)-carboxylic acid, 2-(2'- hydroxynaphth-1'-yl)-Δ2-thiazoline-(4S)-carboxylic acid, 2-(3'- hydroxynaphth-2'-yl)-Δ2-thiazoline-(4R)-carboxylic acid, and 2-(3'- hydroxynaphth-2'-yl)-Δ2-thiazoline-(4S)-carboxylic acid are described. While the bile duct-cannulated rat model clearly demonstrates that the 3'- hydroxynaphth-2'-yl compounds are orally active iron-clearing agents and the corresponding 2'-hydroxynaphthyl-1'-yl compounds are not, in the primate model none of the benz-fused desazadesferrithiocin analogues are active. Oral versus subcutaneous administration of these ligands strongly suggests that metabolism is a key issue in their iron-clearing properties and that these benz-fused desferrithiocins are not good candidates for orally active iron- clearing drugs.
