- Design and optimisation of a small-molecule TLR2/4 antagonist for anti-tumour therapy
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In anti-tumour therapy, the toll-like receptor 2/4 (TLR2/4) signalling pathway has been a double-edged sword. TLR2/4 agonists are commonly considered adjuvants for immune stimulation, whereas TLR2/4 antagonists demonstrate more feasibility for anti-tumour therapy under specific chronic inflammatory situations. In individuals with cancer retaliatory proliferation and metastasis after surgery, blocking the TLR2/4 signalling pathway may produce favourable prognosis for patients. Therefore, here, we developed a small-molecule co-inhibitor that targets the TLR2/4 signalling pathway. After high-throughput screening of a compound library containing 14 400 small molecules, followed by hit-to-lead structural optimisation, we finally obtained the compound TX-33, which has effective inhibitory properties against the TLR2/4 signalling pathways. This compound was found to significantly inhibit multiple pro-inflammatory cytokines released by RAW264.7 cells. This was followed by TX-33 demonstrating promising efficacy in subsequent anti-tumour experiments. The current results provide a novel understanding of the role of TLR2/4 in cancer and a novel strategy for anti-tumour therapy.
- Chen, Hekai,Kong, Jun,Li, Tian,Xu, Qun,Yin, Hang,Zhang, Liwei
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supporting information
p. 1771 - 1779
(2021/11/19)
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- Twist to Boost: Circumventing Quantum Yield and Dissymmetry Factor Trade-Off in Circularly Polarized Luminescence
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Circularly polarized luminescence (CPL) enables promising applications in asymmetric photonics. However, the performances of CPL molecules do not yet meet the requirements of these applications. The shortcoming originates from the trade-off in CPL between the photoluminescence quantum yield (PLQY) and the photoluminescence dissymmetry factor (gPL). In this study, we developed a molecular strategy to circumvent this trade-off. Our approach takes advantage of the strong propensity of [Pt(N^C^N)Cl], where the N^C^N ligand is 1-(2-oxazoline)-3-(2-pyridyl)phenylate, to form face-to-face stacks. We introduced chiral substituents, including (S)-methyl, (R)- and (S)-isopropyl, and (S)-indanyl groups, into the ligand framework. This asymmetric control induces torsional displacements that give homohelical stacks of the Pt(II) complexes. X-ray single-crystal structure analyses for the (S)-isopropyl Pt(II) complex reveal the formation of a homohelical dimer with a Pt···Pt distance of 3.48 ?, which is less than the sum of the van der Waals radii of Pt. This helical stack elicits the metal-metal-to-ligand charge-transfer (MMLCT) transition that exhibits strong chiroptical activity due to the electric transition moment making an acute angle to the magnetic transition moment. The PLQY and gPL values of the MMLCT phosphorescence emission of the (S)-isopropyl Pt(II) complex are 0.49 and 8.4 × 10-4, which are improved by factors of ca. 6 and 4, respectively, relative to the values of the unimolecular emission (PLQY, 0.078; gPL, 2.4 × 10-4). Our photophysical measurements for the systematically controlled Pt(II) complexes reveal that the CPL amplifications depend on the chiral substituent. Our investigations also indicate that excimers are not responsible for the enhanced chiroptical activity. To demonstrate the effectiveness of our approach, organic electroluminescence devices were fabricated. The MMLCT emission devices were found to exhibit simultaneous enhancements in the external quantum efficiency (EQE, 9.7%) and the electroluminescence dissymmetry factor (gEL, 1.2 × 10-4) over the unimolecular emission devices (EQE, 5.8%; gEL, 0.3 × 10-4). These results demonstrate the usefulness of using the chiroptically active MMLCT emission for achieving an amplified CPL.
- Lee, Sumin,Lee, Yongmoon,Kim, Kyungmin,Heo, Seunga,Jeong, Dong Yeun,Kim, Sangsub,Cho, Jaeheung,Kim, Changsoon,You, Youngmin
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p. 7738 - 7752
(2021/05/04)
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- 2-(aryl (azacycloalkane-1-yl) methyl) phenol derivatives and uses thereof
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The invention discloses 2-(aryl (azacycloalkane-1-yl) methyl) phenol derivatives and application thereof, and belongs to the technical field of medicines. The invention provides a compound shown in a formula I or pharmaceutically acceptable salt thereof. The series of compounds have good inhibitory activity on the histone demethylase KDM4 family in vitro, the median inhibitory concentration (IC50) of most molecules on KDM4D is less than 500 nM, and the compounds have good inhibitory effect on proliferation of various human tumor cell strains in vitro, so that the series of compounds provide a new effective choice for developing targeted histone demethylase KDM4D drugs and preparing drugs for treating and/or preventing cancers and reproductive system diseases, and have good application prospects.
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Paragraph 0371-0374; 0375-0377
(2021/07/24)
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- Preparation method of meta-aromatic aldehyde (by machine translation)
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The method, uses an aromatic compound as a raw material, to prepare,bromocarbon, ruthenium catalyst, base and a solvent, wherein the solvent is acetonitrile or, dioxane, which is used as an acylating reagent; to obtain m-substituted aromatic aldehyde; by stirring heating temperature to 1,4 - reaction;hour, separation product in the presence of an alkali, additive, solvent, catalyst. 110 - 130 °C, and a solvent is directly added to the reaction device to obtain a meta-substituted aromatic aldehyde. 20 - 25, The method is convenient and low in cost, by using cheap and C - H easily C - H available, carbon tribromide as an acylating agent under. the ruthenium catalysis action. and a solvent. (by machine translation)
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Paragraph 0008
(2020/03/03)
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- Ruthenium-Catalyzed meta-Selective CAr-H Bond Formylation of Arenes
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The meta-CAr-H bond formylation of arenes has been achieved using CHBr3 as a formyl source in the presence of [Ru(p-cym)(OAc)2] as a catalyst. This method provides efficient access to the preparation of various meta-substituted aromatic compounds, such as alcohols, ethers, amines, nitriles, alkenes, halogens, carboxylic acids, and their derivatives, through transformation of the versatile formyl group. Furthermore, mechanistic studies show that the key active species is a pentagonal ruthenacycle complex.
- Jia, Chunqi,Wu, Nini,Cai, Xiaofeng,Li, Gang,Zhong, Lei,Zou, Lei,Cui, Xiuling
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p. 4536 - 4542
(2020/04/09)
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- Method for preparing meta-position alkenyl aromatic compound
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The invention discloses a method for preparing a meta-position alkenyl aromatic compound. The meta-position alkenyl aromatic compound is prepared from a meta-position formyl aromatic compound and diethyl benzylphosphonate through a reaction, and the reaction comprises steps of directly adding the meta-position formyl aromatic compound, the diethyl benzylphosphonate, ammonium acetate, iodine, peroxytert-butanol, sodium carbonate and ethanol into a reaction device, performing stirring and heating to a temperature of 45-55 DEG C, performing the reaction for 7-9 hours, and separating products, soas to obtain the meta-position alkenyl aromatic compound. By adopting the method, the meta-position alkenyl aromatic compound can be conveniently and rapidly synthesized.
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Paragraph 0008
(2020/02/17)
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- Preparation method of meta-position cyano-aromatic compound
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The invention provides a preparation method of a meta-position cyano-aromatic compound. The meta-position cyano-aromatic compound is obtained by performing reaction on a meta-position formyl-aromaticcompound serving as a raw material and ammonium acetate. The preparation method comprises the following steps: directly adding the meta-position formyl-aromatic compound, the ammonium acetate, iodine,tert-butanol hydrogen peroxide, sodium carbonate and ethanol into a reaction device, stirring and heating to 45 to 55 DEG C, performing reaction for 7 to 9 hours and separating products to obtain themeta-position cyano-aromatic compound. Through the reaction, the meta-position cyano-aromatic compound can be obtained conveniently and rapidly.
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Paragraph 0007-0008; 0013
(2020/02/17)
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- 2-catalyzed directed N -Boc amidation of arenes "on water"
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Rhodium(III) catalysis "on water" is effective for directed C-H amidation of arenes. The catalytic process is promoted by OH groups present on the hydrophobic water surface and is inefficient in all (most) common organic solvents investigated so far. In the presence of easily prepared tert-butyl 2,4-dinitrophenoxycarbamate, a new and stable nitrene source, the "on water" reaction can efficiently provide the desired N-Boc-aminated products with good functional group tolerance.
- Ali, Md Ashif,Yao, Xiayin,Sun, Hao,Lu, Hongjian
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supporting information
p. 1513 - 1516
(2015/03/30)
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- Synthesis of new bioorganometallic Ir- and Rh-complexes having β-lactam containing ligands
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The synthesis (and full spectroscopic and crystallographic characterization) of new classes of bioorganometallic Ir- and Rh-complexes having β-lactam containing ligands has been achieved in three steps starting from simple precursors. The procedure for preparing these bioorganometallic compounds uses β-lactams having a phenylpyridyl moiety attached to the C4, N1 or C4 and N1 positions simultaneously, and a directed C-H metal-insertion, in the presence of (MCp*Cl2)2 (M = Ir, Rh). Enantiomerically pure 2-azetidinones can be transformed into diastereomeric (at the metal) mixtures of enantiopure metalla-2-azetidinones. Bimetallic 2-azetidinones are also accessible by this approach. The insertion of electron-poor alkynes into the M-C bond of the bioorganometallic complex occurs regioselectively and in excellent yields. Overall, the sequence imine-β-lactam-metalla-β-lactam is a versatile and efficient full methodology to prepare and functionalize unprecedented, novel Ir- and Rh-complexes having β-lactam containing ligands.
- Muntaner, Jaime G.,Casarrubios, Luis,Sierra, Miguel A.
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supporting information
p. 286 - 297
(2014/01/06)
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- Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors
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Sant-75 is a newly identified potent inhibitor of the hedgehog pathway. We designed a diversity-oriented synthesis program, and synthesized a series of Sant-75 analogues, which lays the foundation for further investigation of the structure-activity relationship of this important class of hedgehog-pathway inhibitors.
- Che, Chao,Li, Song,Yang, Bo,Xin, Shengchang,Yu, Zhixiong,Shao, Taofeng,Tao, Chuanye,Lin, Shuo,Yang, Zhen
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scheme or table
p. 841 - 849
(2012/07/28)
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- Rh-catalyzed C-C cleavage of benzyl/allylic alcohols to produce benzyl/allylic amines or other alcohols by nucleophilic addition of intermediate rhodacycles to aldehydes and imines
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We report three transformations: 1) direct transformation from biarylmethanols into biarylmethylamines; 2) direct transformation from one biarylmethanol into another biarylmethanol; 3) direct transformation from allylic alcohols into allylic amines. These transformations are based on pyridyl-directed Rh-catalyzed C-C bond cleavage of secondary alcohols and subsequent addition to C=X (X=N or O) double bonds. The reaction conditions are simple and no additive is required. The driving force of C-C bond cleavage is the formation of the stable rhodacycle intermediate. Other directing groups, such as the pyrazolyl group, can also be used although it is not as efficient as the pyridyl group. We carried out in-depth investigations for transformation 1 and found that: 1) the substrate scope was broad and electron-rich alcohols and electron-deficient imines are more efficient; 2) as the leaving group, aldehyde had no significant impact on either the C-C bond cleavage or the whole transformation; 3) mechanistic studies (intermediate isolation, in situ NMR spectroscopic studies, competing reactions, isotopic labeling experiments) implied that: i) The C-C cleavage was very efficient under these conditions; ii) there is an equilibrium between the rhodacycle intermediate and the protonated byproduct phenylpyridine; iii) the addition step of the rhodacycle intermediate to imines was slower than the C-C cleavage and the equilibrium between the rhodacycle and phenylpyridine; iv) the whole transformation was a combination of two sequences of C-C cleavage/nucleophilic addition and C-C cleavage/protonation/C-H activation/nucleophilic addition, with the latter being perhaps the main pathway. We also demonstrated the first example of cleavage of an C(alkenyl)-C(benzyl) bond. These transformations showed the exchange (or substitution) of the alcohol group with either an amine or another alcohol group. Like the "group transplant", this method offers a new concept that can be used to directly synthesize the desired products from other chemicals through reorganization of carbon skeletons.
- Zhang, Xi-Sha,Li, Yang,Li, Hu,Chen, Kang,Lei, Zhi-Quan,Shi, Zhang-Jie
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supporting information
p. 16214 - 16225
(2013/02/21)
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- Multifunctional and reactive enantiopure organometallic helicenes: Tuning chiroptical properties by structural variations of mono- and bis(platinahelicene)s
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Acetylacetonato-platina[6]- and -platina[7]helicenes have been prepared from 2-pyridyl-substituted benzophenanthrene ligands by following a two-step cycloplatination reaction. The photophysical properties (UV-visible absorption and emission behavior) and
- Anger, Emmanuel,Rudolph, Mark,Norel, Lucie,Zrig, Samia,Shen, Chengshuo,Vanthuyne, Nicolas,Toupet, Loic,Williams, J. A. Gareth,Roussel, Christian,Autschbach, Jochen,Crassous, Jeanne,Reau, Regis
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supporting information; scheme or table
p. 14178 - 14198
(2012/01/07)
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- PdCl2(dppf)-catalyzed in situ coupling of 2-hydroxypyridines with aryl boronic acids mediated by PyBroP and the one-pot chemo- and regioselective construction of two distinct aryl-aryl bonds
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We present a PdCl2(dppf)-catalyzed synthesis of 2-arylated pyridine derivatives via the in situ coupling of 2-OH pyridines and boronic acids mediated by PyBroP. In addition, the highly chemo- and regioselective construction of two different aryl-aryl bonds via a one-pot operation has also been demonstrated by the orthogonal use of this method with the Ni-catalyzed Suzuki-Miyaura coupling of phenols.
- Li, Shui-Ming,Huang, Jie,Chen, Guo-Jun,Han, Fu-She
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supporting information; experimental part
p. 12840 - 12842
(2012/01/05)
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- Heterocycles substituted pyridine derivatives and antifungal agent containing thereof
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An object of the present invention is to provide an antifungal agent which has excellent antifungal effects and is superior in terms of its physical properties, safety and metabolic stability. According to the present invention, there is disclosed a compound represented by the following formula (I), or a salt thereof: wherein R1 represents a hydrogen atom, a halogen atom, an amino group, a C1-6 alkyl group, a C1-6 alkoxy group or a C1-6 alkoxy C1-6 alkyl group; R2 represents a hydrogen atom, a C1-6 alkyl group, an amino group or a di C1-6 alkylamino group; one of X and Y is a nitrogen atom while the other is a nitrogen atom or an oxygen atom; ring A represents a 5- or 6-member heteroaryl ring or a benzene ring which may have a halogen atom, or 1 or 2 C1-6 alkyl groups; Z represents a single bond, a methylene group, an ethylene group, an oxygen atom, a sulfur atom, —CH2O—, —OCH2—, —NH—, —CH2NH—, —NHCH2—, —CH2S—, or —SCH2—; R3 represents a hydrogen atom, a halogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 5- or 6-member heteroaryl group, or 5- or 6-member non-aromatic heterocyclic group which may have 1 or 2 substituents; and R4 represents a hydrogen atom or a halogen atom.
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Page/Page column 144
(2010/11/27)
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- Synthesis of novel palladacycles and their application in heck and Suzuki reactions under aerobic conditions
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(Chemical Equation Presented) Design and synthesis of a novel family of furancarbothioamide-based palladacycles are reported herein. These palladacycles are thermally stable, not sensitive to air or moisture, and are applied effectively in the Heck reaction of aryl halides with terminal olefins and in the Suzuki reaction of aryl halides with arylboronic acids. These reactions were performed under aerobic conditions, leading to turnover numbers (TONs) up to 1 × 105.
- Xiong, Zhengchang,Wang, Nengdong,Dai, Mingji,Li, Ang,Chen, Jiahua,Yang, Zhen
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p. 3337 - 3340
(2007/10/03)
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- 6-O-carbamoyl ketolide antibacterials
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6-O-Carbamoyl ketolide antibacterials of the formula: wherein R1, R2, R3, R4, R5, R6, X, X′, Y, and Y′ are as described herein and in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.
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- 6-O-acyl ketolide antibacterials
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6-O-Acyl ketolide antibacterials of the formula: wherein R1, R2, R3, R4, W, X, X′, Y, and Y′ are as described herein and in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.
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- 6-O-carbamate-11,12-lacto-ketolide antimicrobials
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6-O-Carbamate-11,12-lacto-ketolide antimicrobials of the formula: wherein R1, R2, R3 R7, and R8 are as described herein and in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.
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- Biaryl ether derivatives useful as monoamine reuptake inhibitors
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The present invention relates to compounds of formula I, and to their pharmaceutically acceptable salts. Compounds of formula I exhibit activity as serotonin, norepinephrine, and dopamine reuptake inhibitors and can be used in the treatment of central nervous system and other disorders.
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- 6-0-carbamoyl ketolide antibacterials
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6-O-Carbamoyl ketolide antibacterials of the formula: wherein R1, R2, R3, R4, R5, R6, X, X′, Y, and Y′ are as described herein and in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.
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- Novel heteroaryl replacements of aromatic 3-tetrafluoroethoxy substituents in trifluoro-3-(tertiaryamino)-2-propanols as potent inhibitors of cholesteryl ester transfer protein
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A series of novel N,N-disubstituted trifluoro-3-amino-2-propanols has been prepared as potent inhibitors of cholesteryl ester transfer protein (CETP). Modifying the aromatic 3-tetrafluoroethoxy group in the lead molecule 1a with various heteroaryl moietie
- Massa, Mark A.,Spangler, Dale P.,Durley, Richard C.,Hickory, Brian S.,Connolly, Daniel T.,Witherbee, Bryan J.,Smith, Mark E.,Sikorski, James A.
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p. 1625 - 1628
(2007/10/03)
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- SYNTHESIS AND BIOLOGICAL ACTIVITIES OF NEW HMG-COA SYNTHASE INHIBITORS: 2-OXETANONES WITH A SIDE CHAIN CONTAINING BIPHENYL, TERPHENYL OR PHENYLPYRIDINE
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A series of 1233A analogs containing biphenylyl, terphenylyl or phenylpyridyl groups in their side chain were synthesized and tested for the inhibitory activities against 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and inhibition for the chol
- Hashizume, Hirokazu,Ito, Hajime,Kanaya, Naoaki,Nagashima, Hajime,Usui, Hiroyuki,et al.
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p. 1551 - 1572
(2007/10/02)
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