- HETEROCYCLIC COMPOUNDS FOR MODULATING NR2F6
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The present disclosure relates to compounds capable of modulating the activity of NR2F6. The compounds of the disclosure may be used in methods for the prevention and/or the treatment of diseases and disorders associated with modulating NR2F6 activity.
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Paragraph 00429
(2021/09/04)
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- Pro-apoptotic carboxamide analogues of natural fislatifolic acid targeting Mcl-1 and Bcl-2
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A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohexenyl chalcone analogues, six compounds behaved as dual Bcl-xL/Mcl-1 inhibitors in micromolar range and one exhibited sub-micromolar affinities toward Mcl-1 and Bcl-2. The most potent compounds evaluated on A549 and MCF7 cancer cell lines showed moderate cytotoxicities.
- Abou Samra, Alma,Ariffin, Azhar,Awang, Khalijah,Bignon, Jérome,Daressy, Florian,Desrat, Sandy,Fourneau, Christophe,Gapil Tiamas, Shelly,Hoong Leong, Kok,Litaudon, Marc,Roussi, Fanny,Steinmetz, Vincent
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supporting information
(2020/02/13)
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- Asymmetric Total Synthesis and Biological Evaluation of Proapoptotic Natural Myrcene-Derived Cyclohexenyl Chalcones
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Based on a bioinspired asymmetric Diels–Alder cycloaddition using a chiral Evans oxazolidinone, the first total synthesis of both enantiomers of two myrcene-derived cyclohexenyl chalcones, fislatifolione and fislatifolic acid, has been carried out. This strategy was also applied to the total synthesis of nicolaiodesin C. These natural products, as well as their synthetic intermediates, were evaluated by in-vitro affinity displacement assays, based on the modulation of Bcl-xL/Bak, Mcl-1/Bid, and Bcl-2-Bim interactions. This study showed that (+)-fislatifolic acid acts as a dual Bcl-xL/Mcl-1 inhibitor with micromolar activity, and that a Weinreb amide intermediate acts as an excellent Mcl-1/Bcl-2 dual inhibitor at the submicromolar level.
- Tiamas, Shelly Gapil,Audet, Florian,Samra, Alma Abou,Bignon, Jérome,Litaudon, Marc,Fourneau, Christophe,Ariffin, Azhar,Awang, Khalijah,Desrat, Sandy,Roussi, Fanny
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p. 5830 - 5835
(2018/11/24)
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- N-Acylation of Oxazolidinones via Aerobic Oxidative NHC Catalysis
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The first N-acylation of synthetically useful oxazolidinones with aldehydes using aerobic oxidative NHC catalysis is reported. The reaction offers a broad scope of functionalized oxazolidinones in good to excellent yields. Careful choice of electron transfer mediators proved pivotal to achieve efficient aerobic N-acylation, which has previously proven difficult using NHC catalysis. The methodology allows a mild entry to acylated oxazolidinones, avoiding the use of hazardous and reactive prefunctionalized substrates.
- Ta, Linda,Axelsson, Anton,Sundén, Henrik
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p. 12261 - 12268
(2018/09/25)
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- Remarkable dependence of the regioselectivity of free radical additions to 3-cinnamoyloxazolidin-2-ones on the stability of the intermediate adduct-radical, electrophilicity of the adding radicals and the conditions for their generation
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Electrophilic (CCl3) and nucleophilic radicals (Pri) are found to add at 80°C to the C=C bond of 3-(E)-cinnamoyl-4-phenyloxazolidin-2-one 1a and 3-(E)-cinnamoyl-4-benzyloxazolidin-2-one 1b predominantly at the α-position of the bond. While for the CCl3 radical no product of β-addition has been found, for the Pri radical such a path constitutes up to 40% of the whole process at 80°C. An interplay between the stability of the intermediate adduct radicals and the electrophilicity or nucleophilicity of the radicals undergoing addition are invoked to rationalize the observation. At a low temperature (-23°C) β-addition of the Pri radical becomes the dominant process (up to 75%).
- Tararov, Vitali I.,Kuznetzov, Nikolai Yu.,Bakhmutov, Vladimir I.,Ikonnikov, Nikolai S.,Bubnov, Yuri N.,Khrustalev, Victor N.,Saveleva, Tatiana F.,Belokon, Yuri N.
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p. 3101 - 3106
(2007/10/03)
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- A practical method for N-acylation of bornane-2,10-sultam and 2-oxazolidinones
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The N-trimethylsilyl derivatives of (+)-bornane-2,10-sultam (10,10-dimethyl-5-thia-4-azatricyclo[5.2.1.03,7]decane 5,5-dioxide) and (R)-4-benzyl-2-oxazolidinone and 4-methyl-5-phenyl-2-oxazolidinone react with acid chlorides in refluxing benzen
- Thom,Kocienski
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p. 582 - 586
(2007/10/02)
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