- SOLID PHASE SUPPORT FOR NUCLEIC ACID SYNTHESIS AND METHOD FOR PRODUCING NUCLEIC ACID USING THE SAME
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PROBLEM TO BE SOLVED: To provide a solid phase support that can be used in nucleic acid synthesis with high yield, high efficiency and high selectivity, and a method for producing a nucleic acid using the same. SOLUTION: A solid phase support for nucleic
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Paragraph 0099-0100
(2020/11/25)
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- Design, synthesis, and biological evaluation of novel substituted thiourea derivatives as potential anticancer agents for NSCLC by blocking K-Ras protein-effectors interactions
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Mutation of the proto-oncogene K-Ras is one of the most common molecular mechanisms in non-small cell lung cancer. Many drugs for treating lung cancer have been developed, however, due to clinical observed K-Ras mutations, corresponding chemotherapy and targeted therapy for such mutation are not efficient enough. In this study, on the basis of the crystal structure of K-Ras, 21 analogues (TKR01–TKR21) containing urea or thiourea were rationally designed, which can effectively inhibit the lung cancer cell A549 growth. The designing of these compounds was based on the structure of K-Ras protein, and the related groups were replaced by bioisosteres to improve the affinity and selectivity. Biological testing revealed that compound TKR15 could significantly inhibit the proliferation of A549 cell with IC50 of 0.21 μM. Docking analysis showed that the TKR15 can effectively bind to the hydrophobic cavity and form a hydrogen bond with the Glu37. In addition, through flow apoptosis assay and immunofluorescence staining assay, it confirmed that this compound can inhibit A549 cell proliferation with the mechanism of blocking K-RasG12V protein and effector proteins interactions through the apoptotic pathway. In conclusion, our studies in finding novel potent compound (TKR15) with confirmed mechanism showed great potential for further optimisation and other medicinal chemistry relevant studies.
- Cheng, Minghui,Meng, Xin,Tang, Haikang,Xu, Wenqing,Yang, Fujun,Zhang, Yuan
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p. 344 - 353
(2019/12/30)
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- Compound comprising urea and thiourea structures and synthesis method and application of compound
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The invention relates to an organic small molecular compound comprising urea and thiourea structures in a formula I and a synthesis method and application of the compound. According to in-vitro antitumor activity tests, the compound has high antitumor act
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Paragraph 0060; 0062
(2019/08/07)
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- Synthesis and free radical scavenging activity of new hydroxybenzylidene hydrazines
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Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities. Here, we report synthesis and free radical scavenging activity of nine new N-(hydroxybenzylidene)-N0-[2,6-dinitro-4-(trifluoromethyl)]phenylhydrazines. The chemical structures
- Sersen, Frantisek,Gregan, Fridrich,Kotora, Peter,Kmetova, Jarmila,Filo, Juraj,Loos, Dusan,Gregan, Juraj
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- FLUORINATED PHENYL-NAPHTHALENYL-UREA COMPOUNDS AS INHIBITORS OF CYTOKINES INVOLVED IN INFLAMMATORY PROCESSES
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Disclosed are compounds of formula (I) wherein R1, R2, W and X of formula (I) are defined herein. The compounds inhibit production of cytokines involved in inflammatory processes and are thus useful for treating diseases and pathological conditions involving inflammation such as chronic inflammatory disease. Also disclosed are processes for preparing these compounds and pharmaceutical compositions comprising these compounds.
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- Phosphotriesters Approach to the Synthesis of Oligonucleotides: A Reappraisal
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The phosphotriester approach to the synthesis of oligodeoxyribo- and oligoribo-nucleotides in solution has been reinvestigated.The efficacy of mesitylene-2-sulfonyl chloride (MSCl) 15a, 2,4,6-triisopropylbenzenesulfonyl chloride (TrisCl) 15b, 4-bromobenzenesulfonyl chloride 15c, naphthalene-1-sulfonyl chloride 39, and 2- and 4-nitrobenzenesulfonyl chlorides 40a and 40b, respectively, as activating agents has been examined.The latter arenesulfonyl chlorides have been used in conjunction with the following nucleophilic catalysts: 1-methylimidazole, 3-nitro-1H-1,2,4-triazole 19, 5-(3-nitrophenyl)-1H-tetrazole 20a, 5-(3,5-dinitrophenyl)-1H-tetrazole 20b, 5-(1-methylimidazol-2-yl)-1H-tetrazole 21, 5--1H-tetrazole 22, 4-ethoxypyridine 1-oxide 14a, 4,6-dinitro-1-hydroxybenzotriazole 29a, 1-hydroxy-4-nitro-6-(trifluoromethyl)benzotriazole 29b, 1-hydroxy-5-phenyltetrazole 30a and 1-hydroxy-5-(3-nitrophenyl)tetrazole 30b.The rates of formation and yields of the fully protected dideoxyribonucleoside and diribonucleoside phosphates 37 and 47, respectively, were determined using various combinations of activating agents and nucleophilic catalysts.Although 2- and 4-nitrobenzenesulfonyl chlorides 40a and 40b, respectively, proved to be the most powerful activating agents, their use in the deoxy-series led to the formation of by-products and hence to unsatisfactory isolated yields of the dideoxyribonucleoside phosphate 37.
- Reese, Colin B.,Pei-Zhuo, Zhang
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p. 2291 - 2302
(2007/10/02)
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- Rapid Scan Ultraviolet Spectroscopy of the Formation of 1,1- and 1,3-Comlexes. Reaction of 1-Methoxy-2,6-dinitro-4-trifluoromethylbenzene with Piperidine, Pyrrolidine, and n-Butylamine in Dimethyl Sulphoxide
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Rapid scan u.v. spectra for the reactions of 1-methoxy-2,6-dinitro-4-trifluoromethylbenzene with piperidine, pyrrolidine, and n-butylamine in dimethyl sulphoxide have been observed.The formation not only of 1,1-complexes but also of 1,3-complexes has been
- Hasegawa, Yoshinori
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p. 1179 - 1182
(2007/10/02)
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- Stereoelectronic and Conformational Effects in Meisenheimer Complexes. Intrinsic Reactivities of Spiro vs. 1,1-Dimethoxy and 1-Methoxy-1-phenoxy Complexes
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Rate and equilibrium constants of formation of spiro Meisenheimer complexes derived from 1-(2-hydroxyethoxy)-2,6-dinitro-4-X-benzenes in aqueous solution are compared with those for 1,1-dimethoxy Meisenheimer complexes derived from 2,4-dinitro-4-X-anisoles.Hammett ρ values for the equilibrium constants are 8.2 for the dimethoxy and 5.9 for the spiro complexes, while the normalized ρ values for the rate constants of complex formation (cleavage) are 0.44 (-0.56) for the dimethoxy and 0.58 (-0.42) for the spiro complexes.The large difference in the equilibrium ρ values is attributed to a conformation of a dimethoxy complexes in which there is repulsion between the lone pairs on the ketal and the o-nitro group oxygens.A procedure for making the reactions in the two families thermodynamically comparable by correcting the rate and equilibrium constants for the pKa difference in the nucleophile and for intramolecularity of spiro complex formation was applied.The corrected parameters show that the spiro complexes form and decompose much faster than the dimethoxy complexes.This enhanced reactivity, ΔΔG, is attributed to a stereoelectronic effect or p-? overlap between a lone pair orbital of the nonreacting oxygen and the benzene ring, which is only feasible in the transition state of the spiro complex reaction (14) but not in the thransition state of the dimethoxy complex reaction (15).This interpretation is strongly supported by the fact that ΔΔG increases with increasing electron-withdrawing strength of X substituent.The enhanced rate of formation and decomposition of the spiro complex from catehol 2,4,6-trinitrophenyl ether compared to that of the corresponding 1-methoxy-1-phenoxy complex can be explained in a similar way.
- Bernasconi, Claude F.,Howard, Keith A.
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p. 7248 - 7257
(2007/10/02)
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