- Selective hydroboration of alkynes via multisite synergistic catalysis by PCN-222(Cu)
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Zirconium-based porphyrinic MOFs (PMOFs, MOF = metal-organic framework) have gained considerable attention in the field of electric/thermo/photo-catalysis as heterogeneous single-site catalysts; however, the study on multisite synergistic catalysis of PMO
- Ma, L. J.,Tang, Z. Y.,Yuan, J. C.,Zhang, L. J.,Zhang, X. M.
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- Discovery of Aminopyrazole Derivatives as Potent Inhibitors of Wild-Type and Gatekeeper Mutant FGFR2 and 3
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Fibroblast growth factor receptors (FGFR) 2 and 3 have been established as drivers of numerous types of cancer with multiple drugs approved or entering late stage clinical trials. A limitation of current inhibitors is vulnerability to gatekeeper resistance mutations. Using a combination of targeted high-throughput screening and structure-based drug design, we have developed a series of aminopyrazole based FGFR inhibitors that covalently target a cysteine residue on the P-loop of the kinase. The inhibitors show excellent activity against the wild-type and gatekeeper mutant versions of the enzymes. Further optimization using SAR analysis and structure-based drug design led to analogues with improved potency and drug metabolism and pharmacokinetics properties.
- Brawn, Ryan A.,Cook, Andrew,Omoto, Kiyoyuki,Ke, Jiyuan,Karr, Craig,Colombo, Federico,Virrankoski, Milena,Prajapati, Sudeep,Reynolds, Dominic,Bolduc, David M.,Nguyen, Tuong-Vi,Gee, Patricia,Borrelli, Deanna,Caleb, Benjamin,Yao, Shihua,Irwin, Sean,Larsen, Nicholas A.,Selvaraj, Anand,Zhao, Xuesong,Ioannidis, Stephanos
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supporting information
p. 93 - 98
(2020/12/21)
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- Direct Synthesis of Alkenylboronates from Alkenes and Pinacol Diboron via Copper Catalysis
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We report an efficient approach for the direct synthesis of alkenylboronates using copper catalysis. The Cu/TEMPO catalyst system (where TEMPO = (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) exhibits both excellent reactivity and selectivity for the synthesis of alkenylboronates, starting from inexpensive and abundant alkenes and pinacol diboron. This approach allows for the direct functionalization of both aromatic and aliphatic terminal alkenes. Mechanistic experiments suggest that the alkenylboronates arise from oxyboration intermediates.
- Lu, Wenkui,Shen, Zengming
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supporting information
p. 142 - 146
(2019/01/11)
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- Highly selective methods for synthesis of internal (α-) vinylboronates through efficient NHC-Cu-catalyzed hydroboration of terminal alkynes. Utility in chemical synthesis and mechanistic basis for selectivity
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Cu-catalyzed methods for site-selective hydroboration of terminal alkynes, where the internal or α-vinylboronate is generated predominantly (up to >98%) are presented. Reactions are catalyzed by 1-5 mol % of N-heterocyclic carbene (NHC) complexes of copper, easily prepared from N-aryl-substituted commercially available imidazolinium salts, and proceed in the presence of commercially available bis(pinacolato)diboron [B2(pin)2] and 1.1 equiv of MeOH at -50 to -15 °C in 3-24 h. Propargyl alcohol and amine and the derived benzyl, tert-butyl, or silyl ethers as well as various amides are particularly effective substrates; also suitable are a wide range of aryl-substituted terminal alkynes, where higher α-selectivity is achieved with substrates that bear an electron-withdrawing substituent. α-Selective Cu-catalyzed hydroborations are amenable to gram-scale procedures (1 mol % catalyst loading). Mechanistic studies are presented, indicating that α selectivity arises from the structural and electronic attributes of the NHC ligands and the alkyne substrates. Consistent with suggested hypotheses, catalytic reactions with a Cu complex, derived from an N-adamantyl-substituted imidazolinium salt, afford high β selectivity with the same class of substrates and under similar conditions.
- Jang, Hwanjong,Zhugralin, Adil R.,Lee, Yunmi,Hoveyda, Amir H.
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p. 7859 - 7871
(2011/06/27)
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- PYRIMIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF CANCER
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This invention relates to novel compounds (I) and processes for their preparation, methods of treating diseases, particularly cancer, comprising administering said compounds, and methods of making pharmaceutical compositions for the treatment or prevention of disorders, particularly cancer.
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Page/Page column 38-39
(2008/06/13)
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