942220-36-2Relevant academic research and scientific papers
Hydroxypyridinethione Inhibitors of Human Insulin-Degrading Enzyme
Adamek, Rebecca N.,Suire, Caitlin N.,Stokes, Ryjul W.,Brizuela, Monica K.,Cohen, Seth M.,Leissring, Malcolm A.
, p. 1775 - 1787 (2021)
Insulin-degrading enzyme (IDE) is a human mononuclear Zn2+-dependent metalloenzyme that is widely regarded as the primary peptidase responsible for insulin degradation. Despite its name, IDE is also critically involved in the hydrolysis of several other disparate peptide hormones, including glucagon, amylin, and the amyloid β-protein. As such, the study of IDE inhibition is highly relevant to deciphering the role of IDE in conditions such as type-2 diabetes mellitus and Alzheimer disease. There have been few reported IDE inhibitors, and of these, inhibitors that directly target the active-site Zn2+ ion have yet to be fully explored. In an effort to discover new, zinc-targeting inhibitors of IDE, a library of ～350 metal-binding pharmacophores was screened against IDE, resulting in the identification of 1-hydroxypyridine-2-thione (1,2-HOPTO) as an effective Zn2+-binding scaffold. Screening a focused library of HOPTO compounds identified 3-sulfonamide derivatives of 1,2-HOPTO as inhibitors of IDE (Ki values of ～50 μM). Further structure-activity relationship studies yielded several thiophene-sulfonamide HOPTO derivatives with good, broad-spectrum activity against IDE that have the potential to be useful pharmacological tools for future studies of IDE.
Visible-Light-Mediated Synthesis of Amides from Aldehydes and Amines via in Situ Acid Chloride Formation
Iqbal, Naeem,Cho, Eun Jin
, p. 1905 - 1911 (2016/03/15)
An efficient visible-light photocatalysis-based one-pot amide synthesis method was developed; visible-light irradiation of a mixture of an aldehyde, tert-butyl hydrogen peroxide, and N-chlorosuccinimide using a Ru(bpy)3Cl2 photocatalyst afforded an acid chloride, which subsequently reacted with amine to yield the corresponding amide. The reaction was used to synthesize moclobemide and a D3 receptor intermediate.
Development of N -methyl-(2-arylquinolin-4-yl)oxypropanamides as leads to PET radioligands for translocator protein (18 kDa)
Brouwer, Chad,Jenko, Kimberly,Zoghbi, Sami S.,Innis, Robert B.,Pike, Victor W.
, p. 6240 - 6251 (2014/08/18)
Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such studies. There is an unmet need for genotype-insensitive, high-affinity, and moderately lipophilic TSPO ligands that may serve as leads for PET radioligand development. To address this need, we varied the known high-affinity TSPO ligand (l)-N,N-diethyl-2-methyl-3-(2- phenylquinolin-4-yl)propanamide in its aryl scaffold, side chain tether, and pendant substituted amido group while retaining an N-methyl group as a site for labeling with carbon-11. From this effort, oxygen-tethered N-methyl- aryloxypropanamides emerged as new high-affinity TSPO ligands with attenuated lipophilicity, including one example with attractive properties for PET radioligand development, namely N-methyl-N-phenyl-2-{[2-(pyridin-2-yl)quinolin- 4-yl]oxy}propanamide (22a; rat Ki = 0.10 nM; human TSPO genotypes Ki = 1.4 nM; clogD = 4.18). This article not subject to U.S. Copyright. Published 2014 by the American Chemical Society.
3-Amino- and 3-acylamido-2-phosphonopyridines: synthesis by Pd-catalyzed P-C coupling, structure and conversion to pyrido[b]-anellated P{double bond, long}C-N heterocycles
Adam, Mohamed Shaker S.,Kühl, Olaf,Kindermann, Markus K.,Heinicke, Joachim W.,Jones, Peter G.
, p. 7960 - 7967 (2008/12/20)
Palladium catalyzed cross-coupling of 3-amino- and 3-acylamido-2-bromopyridines 1a-f with triethyl phosphite allowed the synthesis of 3-amino- and 3-acylamido pyridine-2-phosphonic acid diethyl esters 2a-f, whereas nickel catalysts, although providing acc
