855294-03-0Relevant articles and documents
Ruthenium-catalyzed reductive amination without an external hydrogen source
Kolesnikov, Pavel N.,Yagafarov, Niyaz Z.,Usanov, Dmitry L.,Maleev, Victor I.,Chusov, Denis
, p. 173 - 175 (2015)
A ruthenium-catalyzed reductive amination without an external hydrogen source has been developed using carbon monoxide as the reductant and ruthenium(III) chloride (0.008-2 mol %) as the catalyst. The method was applied to the synthesis of antianxiety agent ladasten.
Characterization of Conformationally Constrained Benzanilide Scaffolds for Potent and Selective HDAC8 Targeting
Hassan, Muhammad Murtaza,Israelian, Johan,Nawar, Nabanita,Ganda, Giovanni,Manaswiyoungkul, Pimyupa,Raouf, Yasir S.,Armstrong, David,Sedighi, Abootaleb,Olaoye, Olasunkanmi O.,Erdogan, Fettah,Cabral, Aaron D.,Angeles, Fabrizio,Altintas, Rabia,De Araujo, Elvin D.,Gunning, Patrick T.
, p. 8634 - 8648 (2020/09/21)
Histone deacetylases (HDACs) are an attractive therapeutic target for a variety of human diseases. Currently, all four FDA-approved HDAC-targeting drugs are nonselective, pan-HDAC inhibitors, exhibiting adverse side effects at therapeutic doses. Although selective HDAC inhibition has been proposed to mitigate toxicity, the targeted catalytic domains are highly conserved. Herein, we describe a series of rationally designed, conformationally constrained, benzanilide foldamers which selectively bind the catalytic tunnel of HDAC8. The series includes benzanilides, MMH371, MMH409, and MMH410, which exhibit potent in vitro HDAC8 activity (IC50 = 66, 23, and 66 nM, respectively) and up to 410-fold selectivity for HDAC8 over the next targeted HDAC. Experimental and computational analyses of the benzanilide structure docked with human HDAC8 enzyme showed the adoption of a low-energy L-shaped conformer that favors HDAC8 selectivity. The conformationally constrained HDAC8 inhibitors present an alternative biological probe for further determining the clinical utility and safety of pharmacological knockdown of HDAC8 in diseased cells.
Bifunctional Pincer Catalysts for Chemoselective Transfer Hydrogenation and Related Reactions
Cohen, Shirel,Bilyachenko, Alexey N.,Gelman, Dmitri
, p. 3203 - 3209 (2019/02/09)
A comparative study on the chemoselective transfer hydrogenation of nitroarenes to anilines and related processes using FA as the hydrogen source is described; these processes are catalyzed by a series of pincer catalysts equipped with different functional groups in the secondary coordination sphere. Some new (4 and 5) as well as previously reported (1–3) catalysts belonging to the family of bifunctional PC(sp3)P pincer complexes were employed in this study The reported compounds exhibited remarkably different catalytic activity behavior, depending on the nature of the functional groups. Transfer hydrogenation of nitrobenzene with FA as a hydrogen source was probed using iridium complexes 3 or 4 as a catalyst. Under the same conditions, the analogous palladium complex was found to be useful for the selective amidation of aniline with light carboxylic acids.
O -Phenylenediamine: A privileged pharmacophore of ferrostatins for radical-trapping reactivity in blocking ferroptosis
Sheng, Xie-Huang,Cui, Cheng-Cheng,Shan, Chao,Li, Yu-Zhen,Sheng, Duo-Hong,Sun, Bin,Chen, De-Zhan
, p. 3952 - 3960 (2018/06/11)
Ferroptosis is a non-apoptotic, iron dependent form of regulated cell death that is characterized by the accumulation of lipid hydroperoxides. It has drawn considerable attention owing to its putative involvement in diverse neurodegenerative diseases. Ferrostatins are the first identified inhibitors of ferroptosis and they inhibit ferroptosis by efficiently scavenging free radicals in lipid bilayers. However, their further medicinal application has been limited due to the deficient knowledge of the lipid peroxyl radical-trapping mechanism. In this study, experimental and theoretical methods were performed to illustrate the possible lipid hydroperoxide inhibition mechanism of ferrostatins. The results show that an ortho-amine (-NH) moiety from ferrostatins can simultaneously interact with lipid radicals, and then form a planar seven-membered ring in the transition state, and finally present greater reactivity. NBO analysis shows that the formed planar seven-membered ring forces ortho-amines into better alignment with the aromatic π-system. It significantly increases the magnitudes of amine conjugation and improves spin delocalization in the transition state. Additionally, a classical H-bond type interaction was discovered between a radical and an o-NH group as another transition state stabilizing effect. This type of radical-trapping mechanism is novel and has not been found in diphenylamine or traditional polyphenol antioxidants. It can be said that o-phenylenediamine is a privileged pharmacophore for the design and development of ferroptosis inhibitors.
Discovery of new Gram-negative antivirulence drugs: Structure and properties of novel E. coli WaaC inhibitors
Moreau,Desroy,Genevard,Vongsouthi,Gerusz,Le Fralliec,Oliveira,Floquet,Denis,Escaich,Wolf,Busemann,Aschenbrenner
scheme or table, p. 4022 - 4026 (2009/04/06)
Heptosyltransferases such as WaaC represent promising and attractive targets for the discovery of new Gram-negative antibacterial drugs based on antivirulence mechanisms. We report herein our approach to the identification of the first micromolar inhibitors of WaaC and the preliminary SAR generated from this family of 2-aryl-5-methyl-4-(5-aryl-furan-2-yl-methylene)-2,4-dihydro-pyrazol-3-on es identified by virtual screening.
