143328-24-9Relevant articles and documents
Palladium(II)-Catalyzed C(sp2)-H Bond Activation/C-N Bond Cleavage Annulation of N-Methoxy Amides and Arynes
Cheng, Xiu-Fen,Yu, Ting,Liu, Yi,Wang, Nan,Chen, Zhenzhen,Zhang, Guang-Lu,Tong, Lili,Tang, Bo
, p. 2087 - 2092 (2022/04/07)
The Pd(II)-catalyzed C-H bond activation/C-N bond cleavage annulation reaction of N-alkyoxyamide aryne is developed to synthesize 9,10-dihydrophenanthrenone derivatives. This reaction exhibited good functional group compatibility with yields up to 92%. Detailed mechanistic studies showed that the key to C-N bond cleavage is the formed eight-membered palladacycle intermediate undergoing nucleophilic addition to the carbonyl group, which provides a new and practical way for N-alkoxyamide directed C-H bond activation.
Amide compound and derivative thereof, preparation method, pharmaceutical composition and application thereof
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Paragraph 0313; 0314; 0317; 0318, (2021/07/09)
The invention discloses an amide compound and derivative thereof, a preparation method, a pharmaceutical composition and application thereof. The structure of the amide compound is shown as a formula (I). The derivatives of theamide compound relate to a stereoisomer, a tautomer, a metabolite, a metabolic precursor, a prodrug, a solvate, a salt of the solvate, a crystal, a pharmaceutically acceptable salt or a mixture of the above of theamide compound. The amide compound and the derivative thereof have an efficient inhibition effect on indoleamine 2, 3-dioxygenase 1, and can be used for preparing medicines for treating indoleamine 2, 3-dioxygenase 1 mediated immunosuppression related diseases, the prepared medicine can exert the medicine effect at the molecular level and is wide in application, and the synthesis method of the compound is simple, convenient and easy to operate.
GEM-DISUBSTITUTED HETEROCYCLIC COMPOUNDS AND THEIR USE AS IDH INHIBITORS
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Page/Page column 47, (2021/05/15)
The present invention relates to certain gem-disubstituted heterocyclic compounds, which modulate the activity of Isocitrate Dehydrogenase (IDH). The compounds of this invention are therefore useful in treating diseases caused by mutated IDH1 and/or mutat
Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class i HDAC Enzymes and Cancer Cell Proliferation
Tng, Jiahui,Lim, Junxian,Wu, Kai-Chen,Lucke, Andrew J.,Xu, Weijun,Reid, Robert C.,Fairlie, David P.
supporting information, p. 5956 - 5971 (2020/06/05)
AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.
2-Aminopyridine-Based Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Inhibitors: Assessment of Mechanism-Based Safety
Dow, Robert L.,Ammirati, Mark,Bagley, Scott W.,Bhattacharya, Samit K.,Buckbinder, Leonard,Cortes, Christian,El-Kattan, Ayman F.,Ford, Kristen,Freeman, Gary B.,Guimar?es, Cristiano R. W.,Liu, Shenping,Niosi, Mark,Skoura, Athanasia,Tess, David
supporting information, p. 3114 - 3125 (2018/04/23)
Studies have linked the serine-threonine kinase MAP4K4 to the regulation of a number of biological processes and/or diseases, including diabetes, cancer, inflammation, and angiogenesis. With a majority of the members of our lead series (e.g., 1) suffering from time-dependent inhibition (TDI) of CYP3A4, we sought design avenues that would eliminate this risk. One such approach arose from the observation that carboxylic acid-based intermediates employed in our discovery efforts retained high MAP4K4 inhibitory potency and were devoid of the TDI risk. The medicinal chemistry effort that led to the discovery of this central nervous system-impaired inhibitor together with its preclinical safety profile is described.
General and cost-effective synthesis of 1-heteroaryl/arylcycloalkylamines and their broad applications
Zhang, Dehui,Zheng, Hongchao,Wang, Xiaodong
, p. 1941 - 1953 (2016/04/05)
A general and cost-effective route has been developed to synthesize 1-heteroarylsubstituted cycloalkylamines from readily available heteroarylacetate in good yields. This synthesis features a LHMDS promoted cyclization and one-pot hydrolysis/Curtius rearr
Direct lactonization of 2-arylacetic acids through Pd(II)-catalyzed C-H activation/C-O formation
Yang, Mingyu,Jiang, Xingyu,Shi, Wen-Juan,Zhu, Qi-Lei,Shi, Zhang-Jie
supporting information, p. 690 - 693 (2013/04/10)
Palladium-catalyzed direct lactonization of 2-arylacetic acids through a reaction sequence that includes C-H activation/C-O formation is reported. This method provides a concise and efficient pathway to synthesize fully functionalized benzofuranone derivatives, which are highly relevant to bioactive natural and synthetic products.
