20191-76-8Relevant articles and documents
Mild and Selective Method of Bromination of Flavonoids
Hurtová, Martina,Biedermann, David,Kuzma, Marek,K?en, Vladimír
, p. 3324 - 3331 (2020)
A new method was developed for the mild and selective bromination of simple aromatic compounds and flavonoids in good yields using α,β-dibromohydrocinnamic acid in the presence of a base. This procedure enables selective mono- or dibromination of compounds highly sensitive to oxidative or radical attack. New brominated derivatives of silymarin flavonolignans and related flavonoids were prepared. These brominated derivatives can be used as valuable synthetic intermediates in further synthesis.
Kras-G12C inhibitor heterocyclic compounds
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Paragraph 0165-0171, (2021/06/23)
The invention relates to Kras-G12C inhibitor heterocyclic compounds represented by formula I, a preparation method thereof, and application of the Kras-G12C inhibitor heterocyclic compounds in prevention and treatment of tumor diseases such as lung cancer, colorectal cancer and pancreatic cancer. In the preparation process, the compounds of the general formula I are obtained through a series of reactions such as SN2 reaction, protection, coupling reaction, deprotection, condensation reaction and the like.
KRAS G12C INHIBITORS
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Paragraph 0253; 0278, (2020/03/23)
The present invention relates to compounds that, inhibit KRas G12C, In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
KRAS G12C INHIBITORS
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Paragraph 0249; 0274, (2020/07/25)
The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
Anthracene derivatives compounds and organic electroluminescent devices comprising the same
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Paragraph 0197-0202, (2020/07/28)
The present invention relates to a novel organic electroluminescent compound which is represented by the following [chemical formula 1] or [chemical formula 2]. The electroluminescent compound according to the present invention has high glass transition temperature, thereby having enhanced thermal stability; and can form an organic electroluminescent device having low driving voltage, high luminance, high color purity, and long-life when applying the same to the electroluminescent device.
KRAS G12C INHIBITORS
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Paragraph 0355-0356, (2019/05/24)
The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
PYRAZOLE-CONTAINING MACROPHAGE MIGRATION INHIBITORY FACTOR INHIBITORS
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Page/Page column 100, (2019/10/04)
In one aspect, the invention comprises compounds that bind and inhibit macrophage migration inhibitory factor. In another aspect, the invention provides methods of treating inflammatory disease, neurological disorders and cancer using the compounds of the invention.
Discovery of Novel Naphthylphenylketone and Naphthylphenylamine Derivatives as Cell Division Cycle 25B (CDC25B) Phosphatase Inhibitors: Design, Synthesis, Inhibition Mechanism, and in Vitro Efficacy against Melanoma Cell Lines
Cerchia, Carmen,Nasso, Rosarita,Mori, Matteo,Villa, Stefania,Gelain, Arianna,Capasso, Alessandra,Aliotta, Federica,Simonetti, Martina,Rullo, Rosario,Masullo, Mariorosario,De Vendittis, Emmanuele,Ruocco, Maria Rosaria,Lavecchia, Antonio
, p. 7089 - 7110 (2019/08/20)
CDC25 phosphatases play a critical role in the regulation of the cell cycle and thus represent attractive cancer therapeutic targets. We previously discovered the 4-(2-carboxybenzoyl)phthalic acid (NSC28620) as a new CDC25 inhibitor endowed with promising anticancer activity in breast, prostate, and leukemia cells. Herein, we report a structure-based optimization of NSC28620, leading to the identification of a series of novel naphthylphenylketone and naphthylphenylamine derivatives as CDC25B inhibitors. Compounds 7j, 7i, 6e, 7f, and 3 showed higher inhibitory activity than the initial lead, with Ki values in the low micromolar range. Kinetic analysis, intrinsic fluorescence studies, and induced fit docking simulations provided a mechanistic understanding of the activity of these derivatives. All compounds were tested in the highly aggressive human melanoma cell lines A2058 and A375. Compound 4a potently inhibited cell proliferation and colony formation, causing an increase of the G2/M phase and a reduction of the G0/G1 phase of the cell cycle in both cell lines.
Making endo-cyclizations favorable again: A conceptually new synthetic approach to benzotriazoles via azide group directed lithiation/cyclization of 2-azidoaryl bromides
Ageshina, Alexandra A.,Chesnokov, Gleb A.,Topchiy, Maxim A.,Alabugin, Igor V.,Nechaev, Mikhail S.,Asachenko, Andrey F.
supporting information, p. 4523 - 4534 (2019/05/17)
Although benzotriazoles are important and ubiquitous, currently there is only one conceptual approach to their synthesis: bridging the two ortho-amino groups with an electrophilic nitrogen atom. Herein, we disclose a new practical alternative-the endo-cyclization of 2-azidoaryl lithiums obtained in situ from 2-azido-aryl bromides. The scope of the reaction is illustrated using twenty-four examples with a variety of alkyl, alkoxy, perfluoroalkyl, and halogen substituents. We found that the directing effect of the azide group allows selective metal-halogen exchange in aryl azides containing several bromine atoms. Furthermore, (2-bromophenyl)diazomethane undergoes similar cyclization to give an indazole. Thus, cyclizations of aryl lithiums containing an ortho-X = Y = Z group emerge as a new general approach for the synthesis of aromatic heterocycles. DFT computations suggested that the observed endo-selectivity applies to the anionic cyclizations of other functionalities that undergo "1,1-additions" (i.e., azides, diazo compounds, and isonitriles). In contrast, cyclizations with the heteroatomic functionalities that follow the "1,2-addition" pattern (cyanates, thiocyanates, isocyanates, isothiocyanates, and nitriles) prefer the exo-cyclization path. Hence, such reactions expand the current understanding of stereoelectronic factors in anionic cyclizations.
MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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Paragraph 001224-001225, (2019/10/29)
The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
