- STRAD-BINDING AGENTS AND USES THEREOF
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Disclosed herein, inter alia, are compounds for binding STRAD pseudokinase and uses thereof.
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Paragraph 0772-0774
(2021/08/06)
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- Rhodium-Catalyzed Rearrangement of S/Se-Ylides for the Synthesis of Substituted Vinylogous Carbonates
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An efficient rhodium-catalyzed unprecedented oxa-[2,3]-sigmatropic rearrangement of sulfur ylide derived from α-thioesters/ketones and diazo carbonyl compounds has been accomplished for the synthesis of various sulfur-tethered vinylogous carbonates in good to excellent yields. Important features of the developed reaction include wide functional group tolerance, excellent chemo- and regioselectivity, and efficient rearrangement involving the carbonyl motif. The present reaction also equally works well with α-selenoesters for the synthesis of seleno-containing vinylogous carbonates.
- Reddy, Angula Chandra Shekar,Anbarasan, Pazhamalai
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supporting information
p. 9965 - 9969
(2019/12/24)
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- Structure-based modification of carbonyl-diphenylpyrimidines (Car-DPPYs) as a novel focal adhesion kinase (FAK) inhibitor against various stubborn cancer cells
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A family of carbonyl-substituted diphenylpyrimidine derivatives (Car-DPPYs) with strong activity against focal adhesion kinase (FAK), were described in this manuscript. Among them, compounds 7a (IC50 = 5.17 nM) and 7f (IC50 = 2.58 nM) displayed equal anti-FAK enzymatic activity to the lead compound TAE226 (6.79 nM). In particular, compound 7a also exhibited strong antiproliferative activity against several stubborn cancer cells, including AsPC-1 cells (IC50 = 0.105 μM), BxPC-3 cells (IC50 = 0.090 μM), and MCF-7/ADR cells (IC50 = 0.59 μM). Additionally, compound 7a also showed great antitumor efficacy in vivo via aAsPC-1 cancer Xenograft mouse model. The preliminary mechanism study by Western blot analysis revealed that 7a repressed FAK phosphorylation in AsPC cancer cells. Taken together, the results indicate that compound 7a may serve as a promising preclinical candidate for treatment of stubborn cancers.
- Wang, Luhong,Ai, Min,Yu, Jiawen,Jin, Lingling,Wang, Changyuan,Liu, Zhihao,Shu, Xiaohong,Tang, Zeyao,Liu, Kexin,Luo, Hui,Guan, Wenshun,Sun, Xiuli,Ma, Xiaodong
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p. 154 - 162
(2019/04/13)
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- Structural optimization of diphenylpyrimidine scaffold as potent and selective epidermal growth factor receptor inhibitors against L858R/T790M resistance mutation in nonsmall cell lung cancer
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A new class of thiodiphenylpyrimidine analogs (Thio-DPPY) were synthesized as potent and selective EGFR T790M inhibitors to overcome gefitinib resistance in nonsmall cell lung cancer (NSCLC). This structural optimization led to the identification of two p
- Yi, Yuanyuan,Wang, Luhong,Zhao, Dan,Huang, Shanshan,Wang, Changyuan,Liu, Zhihao,Sun, Huijun,Liu, Kexin,Ma, Xiaodong,Li, Yanxia
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p. 1988 - 1997
(2018/09/06)
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- Scope and Mechanism of Iridium Porphyrin-Catalyzed S-H Insertion Reactions between Thiols and Diazo Esters
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The insertion of carbenes derived from ethyl diazoacetate (EDA), methyl diazoacetate (MDA), methyl phenyldiazoacetate (MPDA), and methyl (p-tolyl)diazoacetate (MTDA) into the S-H bonds of aromatic and aliphatic thiols was catalyzed by (5,10,15,20-tetratolylporphyrinato)methyliridium(III), Ir(TTP)CH3, at ambient temperatures. Yields of the resulting thioether products were as high as 97% for aromatic thiols, with catalyst loadings as low as 0.07 mol %. Thiol binding to Ir(TTP)CH3 was measured at 23 °C by titration studies, providing equilibrium constants, Kb, ranging from 4.25 × 102 to 1.69 × 103 and increasing in the order p-nitrobenzenethiol a mechanism that involves a rate-limiting nucleophilic attack of thiols on an iridium-carbene species, where the major species present in the reaction solution is an inactive, hexacoordinate Ir-thiol complex.
- Dairo, Taiwo O.,Woo, L. Keith
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p. 927 - 934
(2017/04/21)
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- Synthesis of thioether andrographolide derivatives and their inhibitory effect against cancer cells
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A series of novel thioether andrographolide derivatives were synthesized by incorporating various aromatic (or heteroaromatic) substituents into C-12 or 14-OH. A total of 38 andrographolide derivatives were prepared and evaluated for their in vitro inhibi
- Liu, Yi,Liang, Ren-Ming,Ma, Qing-Ping,Xu, Kai,Liang, Xin-Yong,Huang, Wei,Sutton, Robert,Ding, Jie,O'Neil, Paul M.,Cheng, Chun-Ru
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p. 1268 - 1274
(2017/07/07)
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- MATRIX METALLOPROTEINASE INHIBITORS
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This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, pulmonary inflammation, acute respiratory distress syndrome, periodontitis, multiple sclerosis, gingivitis, gingivitis, atherosclerosis, dry eye, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and pounds.
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Paragraph 0410; 0411
(2014/06/11)
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- MATRIX METALLOPROTEINASE INHIBITORS
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The present invention relates to certain sulfone acetic acid derivatives of formula I as MMP inhibitor and processes for its syntheses. The invention also relates to pharmacological compositions containing the compounds of the present invention and method
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Page/Page column 39
(2012/04/10)
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- MATRIX METALLOPROTEINASE INHIBITORS
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This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, dry eye, neointimal proliferation, which leads to restenosis and ischemic heart faliure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by over-expression and over-activation of matrix metalloproteinase using the compounds.
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Page/Page column 47
(2012/04/10)
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- Highly stereoselective asymmetric pummerer reactions that incorporate intermolecular and intramolecular nonbonded S...O interactions
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New chiral sulfoxides (RS,S)-3, (SS,S)-3, (R S,S)-4, and (SS,S)-4 and known chiral sulfoxides (R S)-5, (RS)-6, and (RS)-7 were synthesized, and the stereochemistry of the new sulfoxides (RS,S)-3 and (R S,S)-4 was determined by X-ray crystallographic analysis. In their crystallographic structures, the intramolecular nonbonded S...O close contacts were recognized. Analyses of several sulfoxide complexes including rac-11 with N,N-dimethylacetamide (DMAC) or N-methyl-2-pyrrolidone (NMP) in a MeOH solution utilizing cold-spray ionization mass spectrometry provided, for the first time, direct information for intermolecular nonbonded S...O interactions between sulfoxides and amide (or lactam) in a solution. Highly diastereoselective and enantioselective Pummerer reactions based on the concept of intermolecular and intramolecular nonbonded S...O interactions were performed by treatment of several chiral sulfoxides (RS, S)-3, (SS, S)-3, (RS, S)-4, (SS, S)-4, (R S)-5, (RS)-6, and (RS)-7 with acetic anhydride and trimethylsilyl triflate (TMSOTf) in DMAC, NMP, N,N-dimethylformamide, and N-formylpiperidine. Mechanistic studies on these facile stereoselective Pummerer reactions revealed the necessity for the amide/TMSOTf complex, such as 26 or 27, to be an efficient activation reagent for Ac2O and a trapping reagent for the released acetate ion, and that DMAC and NMP had a positive effect on this highly stereoselective chiral transfer reaction.
- Nagao, Yoshimitsu,Miyamoto, Satoshi,Miyamoto, Motoyuki,Takeshige, Hiroe,Hayashi, Kazuhiko,Sano, Shigeki,Shiro, Motoo,Yamaguchi, Kentaro,Sei, Yoshihisa
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p. 9722 - 9729
(2007/10/03)
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- Synthesis of 4-nitrophenyl sulfones and application in the modified Julia olefination
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4-Nitrophenyl (NP) sulfones have been successfully employed in the modified Julia olefination reaction with carbonyl compounds. The olefination reaction proceeds through a sequence of aldol addition, Smiles rearrangement, and elimination. The sulfones are easily prepared in high yields in a two-step sequence starting from inexpensive commercially available para- fluoronitrobenzenes via nucleophilic aromatic substitution by a mercaptane and subsequent oxidation under standard conditions. The modified Julia reaction between NP sulfones and a wide variety of aromatic aldehydes affords the corresponding styrenes, stilbenes and cinnamate derivatives in yields up to 97% and good stereoselectivities. A mechanistic rationale is advanced to explain the observed results. Georg Thieme Verlag Stuttgart.
- Mirk, Daniela,Grassot, Jean-Marie,Zhu, Jieping
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p. 1255 - 1259
(2007/10/03)
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- SYNTHESIS AND SPECTRAL STUDIES OF SOME NOVEL ETHYL (SUBSTITUTED PHENYLTHIO) ACETATE AND PROPIONATE DERIVATIVES
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Ethyl (substituted phenylthio) acetate and propionate derivatives have been synthesised, their structures were proved by IR, NMR and mass spectra.Key words: Arylthioacetates; arylthiopropionates; NMR- and mass spectra
- Hamed, Ezzat E.,El-Bardan, A. A.,Moussa, Adel M.
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p. 269 - 274
(2007/10/02)
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- Neighboring-Group Participation by Hydroxyl Oxygen in Nucleophilic Aromatic Substitution. Smiles Rearrangements of (ω-Hydroxyalkyl)methyl(p-nitrophenyl)sulfonium Perchlorates in Aqueous Alkali
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(2-Hydroxyethyl)- (1), (3-hydroxy-n-propyl)- (2), and (4-hydroxy-n-butyl)methyl(p-nitrophenyl)sulfonium perchlorates (3) were prepared.Products by Smiles rearrangements (intramolecular SNAr reactions) were obtained from 1 as β-(methylthio)ethyl p-nitrophenyl ether (9) in 37-42percent yield and from 2 as γ-(methylthio)propyl p-nitrophenyl ether (8) in quantitative yields, and none were obtained from 3.The rearrangement rates and yields were compared with an intermolecular SN2 reaction of dimethyl(p-nitrophenyl)sulfonium perchlorate (4) (displacement of the sulfonium group by a n-propoxy group) to estimate participation by the ω-hydroxyl oxygen.The rate ratios between the rearrangements (first order) and the SN2 n-propoxy attack (second order), effective molarities, were obtained as 6.02 * 103 M for 1 vs. 4 and 4.64 * 103 M for 2 vs. 4.
- Irie, Tadashi,Tanida, Hiroshi
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p. 4961 - 4965
(2007/10/02)
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