- Pyridone derivative and application thereof in preparation of medicine for preventing and/or treating tuberculosis caused by Mycobacterium tuberculosis
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The invention provides a pyridone derivative and application thereof in preparation of a medicine for preventing and/or treating tuberculosis caused by mycobacterium tuberculosis, which belong to the field of pharmacy. The structure of the pyridone derivative is shown as a formula (I). Experimental results show that the pyridone derivative provided by the invention can specifically inhibit the activity of mycobacterium tuberculosis, has small toxic and side effects, can be used for preparing a medicine for resisting mycobacterium tuberculosis, can also be used for preparing a medicine for preventing and/or treating tuberculosis, and a new choice is provided for medicines for treating tuberculosis (especially drug-resistant tuberculosis).
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- SKLB1039 Compound as well as preparation method and application thereof
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The invention belongs to the technical field of preparation of new compounds, and particularly relates SKLB1039 compound as well as a preparation method and application thereof. The 2 -methyl -3 -nitrobenzoic acid is taken as an initial raw material and is brominated. Esterification, reduction, reductive amination and hydrolysis synthesis 5 - bromo -2 - methyl -3 - (N - ethyl, N - (tetrahydropyran -4 - yl)) aminobenzoic acid. The cyclohexanone serving as a raw material is subjected to catalytic hydrogenation reduction of carbonyl α, acetyl cyclohexanone and cyanopyridone to synthesize 4 - aminomethyl -1 - methyl -5, 6, 7, 8 - tetrahydroisoquinoline -3 (2H) - ketone. Coupling the two to an amide is followed by catalytic coupling with an aryl sheet to give SKLB1039 a compound. SKLB1039 Large-scale preparation technology is provided, operation is easy, the post-treatment purification process is simple, the total route yield is improved, raw materials are easy to purchase, the price is low, and the production cost is greatly reduced.
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Paragraph 0030; 0039; 0065-0069
(2021/10/27)
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- Discovery of quinolone derivatives as antimycobacterial agents
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Tuberculosis (TB), an infectious disease caused byMycobacterium tuberculosis(M. tuberculosis), is an important public health issue. Current first-line drugs administered to TB patients have been in use for over 40 years, whereas second-line drugs display strong side effects and poor compliance. Additionally, designing effective regimens to treat patients infected with multi- and extremely-drug-resistant (MDR and XDR) strains of TB is challenging. In this report, we screened our compound library and identified compound1with antituberculosis activity and a minimal inhibitory concentration (MIC) againstM. tuberculosisof 20 μg mL?1. Structure optimization and the structure-activity relationship of1as the lead compound enabled the design and synthesis of a series of quinolone derivatives,6a1-6a2,6b1-6b36,6c1,6d1-6d14,7a1-7a2,7b1-7b2,7c1,8a1-8a5,9a1-9a4and10a1-10a6. These compounds were evaluatedin vitrofor anti-tubercular activity against theM. tuberculosisH37Rv strain. Among them, compounds6b6,6b12and6b21exhibited MIC values in the range of 1.2-3 μg mL?1and showed excellent activity against the tested MDR-TB strain (MIC: 3, 2.9 and 0.9 μg mL?1, respectively). All three compounds were non-toxic toward A549 and Vero cells (>100 and >50 μg mL?1, respectively). In addition, an antibacterial spectrum test carried out using compound6b21showed that this compound specifically inhibitsM. tuberculosis. These can serve as a new starting point for the development of anti-TB agents with therapeutic potential.
- Gao, Chao,Li, Xiao,Liu, Kun-Lin,Teng, Fei,Xiong, Lu,Yu, Luo-Ting
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p. 24095 - 24115
(2021/07/29)
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- ONE-STEP, FAST, 18F-19F ISOTOPIC EXCHANGE RADIOLABELING OF DIFLUORO-DIOXABORININS AND USE OF SUCH COMPOUNDS IN TREATMENT
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A compound according to Formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, wherein X1 and X2 are each independently 18F or 19F; R1 and R2 are each independently alkyl, amine, perfluoroalkyl, alkenyl, alkynyl, aryl, or aralkenyl; and R3 is H, halo, alkyl, alkyl ester, alkenyl, alkynyl, aryl, or aralkenyl; or wherein: R1 and R3 or R2 and R3 join to form a 6-membered cycloalkyl or heterocyclyl; or R1 and R3, R2 and R3, or R1, R2, and R3 join to form a substituted or unsubstituted polycyclic ring, wherein the polycyclic ring comprises fused cycloalkyl, heterocycloalkyl, aryl, or heteroaryl rings.
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Paragraph 0019; 0202-0203
(2019/12/15)
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- One-pot method for preparation of 2-acetyl cyclohexanone
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The invention discloses a one-pot method for preparation of 2-acetyl cyclohexanone. The method comprises the steps of: (1) adding cyclohexanone into tetrahydrofuran, under the condition of icewater bath cooling, adding lithium diisopropylamide dropwise, and then carrying out stirring reaction at room temperature for 1h; (2) under the condition of icewater bath, adding a trichloromethane solution of acetyl chloride into the reaction system of step (1) dropwise, then removing icewater bath, and carrying out stirring reaction at room temperature for 1h; and (3) washing the reaction solution obtained in step (2) twice and performing liquid separation, conducting spin drying of trichloromethane, then carrying out pressure reduced distillation and collecting 118-136DEG C fractions, thus obtaining 2-acetyl cyclohexanone. According to the method, in the whole reaction process, the intermediate products have no need for additional purification treatment and can be directly subjected to next step reaction, and the finally obtained product is refined directly by pressure reduced distillation. The whole process has the advantages of high yield, short reaction time, and low energy consumption. The 2-acetyl cyclohexanone obtained by direct pressure reduced distillation refining has a concentration of more than 96.0wt%, and the yield is more than 94%.
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Paragraph 0009; 0024-0027
(2017/05/27)
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- Design, synthesis and biological evaluation of novel 1-methyl-3-oxo-2,3,5,6,7,8-hexahydroisoquinolins as potential EZH2 inhibitors
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The histone lysine methyltransferase EZH2 has been implicated as a key component in cancer aggressiveness, metastasis and poor prognosis. This study discovered a new class of hexahydroisoquinolin derivatives as EZH2 inhibitors. A structure-activity relationship study showed that the steric hindrance was important to the activity for EZH2. A preliminary optimization study led to the discovery of several potent compounds with low nanomolar to sub-nanomolar potency for EZH2. Biological evaluation indicated that SKLB1049 was a highly potent with improved solubility compared to EPZ6438, SAM-competitive, and cell-active EZH2 inhibitor that decreased global H3K27me3 in SU-DHL-6 and Pfeiffer lymphoma cells in a concentration- and time-dependent manner. Further study indicated that SKLB1049 caused cell arrest in G0/G1 phase. These compounds would be useful as chemical tools to further explore the biology of EZH2 and provided us with a start point to develop new EZH2 inhibitors.
- Zhang, Lidan,Song, Xuejiao,Wang, Ningyu,Zhao, Lifeng,Feng, Qiang,You, Xinyu,Peng, Cuiting,Gao, Tiantao,Xiong, Menghua,He, Bing,Gao, Chao,Luo, Yong,Xu, Ying,Zhang, Qiyi,Yu, Luoting
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p. 25967 - 25978
(2015/10/20)
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- Titanium silicates as efficient catalyst for alkylation and acylation of silyl enol ethers under liquid-phase conditions
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The activity of titanium- and tin-silicate samples such as TS-1, TS-2, Ti-β and Sn-MFI has been investigated for acylation and alkylation of silyl enol ethers under mild liquid-phase conditions. Silyl enol ethers successfully react with acetyl chloride and tert-butyl chloride under dry conditions in the presence of above catalysts to produce the corresponding acylated and alkylated products, respectively. In the case of acetylation reaction, two different nucleophiles with carbon-center (C-atom) and oxygen-center (O-atom) in silyloxy group of silyl enol ether reacts with acetyl chloride to give 1,3-diketone and ketene-ester, respectively. The selectivity for alkylation is always ca. 100% and no side products are formed. Among the various solvents investigated, anhydrous THF was found to be the suitable solvent for alkylation; whereas dichloromethane exhibited high selectivity for diketones for acylation. The formation of nucleophiles from silyl enol ethers appears to be the key step for successful acetylation and tert-butylation by nucleophilic reaction mechanism. Sn-MFI showed less activity than that observed over the titanosilicates. The observed catalytic activity is explained on the basis of "oxophilic Lewis acidity" of titanium silicate molecular sieves in the absence of H 2O under dry reaction conditions.
- Sasidharan, Manickam,Bhaumik, Asim
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experimental part
p. 87 - 93
(2011/10/12)
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- New bicyclic dioxanes, their preparation and their use as organoleptic compounds
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The present invention relates to novel 1,3-dioxane derivatives of formula (I) wherein each of R1 and R2 is a hydrogen atom, R3 and R4 are independently a hydrogen atom, a linear or branched C1-C6 alkyl group, or a linear or branched C2-C6 alkenyl group, and R5 is a linear or branched C1-C6 alkyl group, a linear or branched C2-C6 alkenyl group or a (CH2)0-2 - aryl group, and R6 and R7 are independently a hydrogen atom, a linear or branched C1-C6 alkyl group, a linear or branched C2-C6 alkenyl group or a (CH2)0-2 - aryl group, or R6 and R7 together with the carbon atom to which they are attached form a C5-C6 cycloalkyl group or a C5-C6 cycloalkenyl group, substituted or not; their preparation and their use as organoleptic compounds.
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- NEW BICYCLIC DIOXANES, THEIR PREPARATION AND THEIR USE AS FRAGRANT COMPOUNDS
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The invention is directed to the use of compounds of formula (I), as fragrant agents. In this formula: - R3 and R4 are independently a hydrogen atom, a C1-C6 alkyl group or a C2-C6 alkenyl group, R5 is a C1-C6 alkyl group, a C2-C6 alkenyl group or a (CH2)0-2-aryl group, R6 is a C1 -C6 alkyl group, a C2-C6 alkenyl group, a (CH2)0-2-aryl group or a C5- C6 cycloalkyl or cycloalkenyl group, and R7 is a hydrogen atom, a C1-C6 alkyl group or a C2-C6 alkenyl group; or R3, R4 and R5 are as above defined, and R6 and R7 together with the carbon atom to which they are attached form a C5-C6 cycloalkyl or cycloalkenyl group.
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Page/Page column 10
(2011/02/24)
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- INDICYANINE DYES AND THE DERIVATIVES THEREOF FOR ANALYSING BIOLOGICAL MICROMOLECULES
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The invention relates to two series of synthesised indolenine pentamethine dyes (37 compounds) comprising a reactive group in the third and fifth positions of the indolenine cycle, respectively. A method for producing, extracting and purifying the dyes and the precursors thereof, consisting in determining the absorption and fluorescence maxima, molecular extinction factors, fluorescence quantum yields, relative fluorescence effectiveness at excitation on a wavelength of 635 nm (detection of 670 nm) and 655 nm (detection of 690 nm), relative light stability and comparative sensitivity of detection of marked oligonucleotides on biochips of the claimed dyes, is disclosed. The use of the claimed dyes in the form of fluorescent marks for oligonucleotide and protein chips is also disclosed.
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Page/Page column 38-39
(2010/04/23)
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- Evaluation of TCS/ZnCl2 with acetic anhydride as an acetylating reagent for methylene ketones
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A new route for the preparation of β-diketones which have applications in organic synthesis by the reaction of methylene ketones, acetic anhydride, TCS and ZnCl2 in the solvent methylene chloride at room temperature produces the corresponding β-diketones in excellent yield. Copyright Taylor & Francis Inc.
- Elmorsy, Saad S.,Badawy, Doria S.,Khatab, Tamer K.
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p. 109 - 116
(2007/10/03)
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- Solvent effects versus concentration effects in determining rates of base-catalyzed keto-enol tautomerization
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Solvent effects of homogeneous media (such as solvent-water mixtures) on chemical reactivity may be interpreted as due to solvent polarity and/or molecular structure of solvent molecules. In microheterogeneous media (such as aqueous micellar solutions), solvent effects on reaction rates must include concentration effects, in addition to changes in the solvent polarity of the micelle interface where the reaction is assumed to occur. In this work, we measured the rates of keto-enol tautomerization of the 2-acetylcyclohexanone (ACHE) and 2-acetyl-1-tetralone (ATLO) systems in dimethylsulfoxide (DMSO)-water mixtures and in aqueous micellar solutions with both anionic and cationic surfactants and in the presence of buffers. The results appear as an ideal framework to understand the paramount importance of the specific molecular structure of solvent molecules in determining chemical reactivity versus solvent polarity or even concentration effects. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2005.
- Iglesias, Emilia
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p. 625 - 632
(2007/10/03)
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- Mechanism of the palladium-catalyzed intramolecular hydroalkylation of 7-octene-2,4-dione
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Cyclization of (E)-7,8-dideuterio-7-octene-2,4-dione [(E)-1-7,8-d2] catalyzed by PdCl2(CH3CN)2 (2) formed cis-2-acyl-3,4-dideuteriocyclohexanone (cis-3-3,4-d2) in 64% yield as the exclusive isotopomer. This experiment, in conjunction with additional deuterium labeling experiments, was in accord with a mechanism for the conversion of 1 to 3 catalyzed by 2 involving attack of the enol carbon atom on a palladium-complexed olefin followed by palladium migration and protonolysis from a palladium enolate complex. Copyright
- Qian, Hua,Widenhoefer, Ross A.
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p. 2056 - 2057
(2007/10/03)
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- Palladium-catalyzed intramolecular oxidative alkylation of unactivated olefins
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Reaction of 5,5-dimethyl-8-nonene-2,4-dione catalyzed by PdCl2(CH3CN)2 (5 mol %) in the presence of CuCl2 (2.5 equiv) at room temperature for 3 h formed 2-acetyl-3,6,6-trimethyl-2-cyclohexenone in 96% isolated yield. Palladium-catalyzed intramolecular oxidative alkylation tolerated a range of substitution and was applicable to the synthesis of spirobicyclic compounds and to the cyclization of ζ-alkenyl β-keto esters. Copyright
- Pei, Tao,Wang, Xiang,Widenhoefer, Ross A.
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p. 648 - 649
(2007/10/03)
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- Lanthanide triflate-promoted palladium-catalyzed cyclization of alkenyl β-keto esters and amides
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(Matrix presented) Lanthanide triflates were found to promote the palladium-catalyzed cyclization of alkenyl β-keto esters and amides. In the presence of catalytic amounts of PdCl2(MeCN)2 and Ln(OTf)3, various alkenyl β-keto esters and amides underwent regioselective cyclization reactions to give six-, seven-, or eight-membered-ring carbocycles in moderate to excellent yields.
- Yang, Dan,Li, Jin-Heng,Gao, Qiang,Yan, Yi-Long
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p. 2869 - 2871
(2007/10/03)
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- Method for preparing chiral diphosphines
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The invention concerns a method for preparing a compound of formula (1) wherein: A represents naphthyl or phenyl optionally substituted; and Ar1, Ar2independently represent a saturated or aromatic carbocyclic group, optionally substituted.
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- Tautomerization of 2-acetylcyclohexanone. 1. Characterization of keto-enol/enolate equilibria and reaction rates in water
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The keto-enol tautomerism of 2-acetylcyclohexanone (ACHE) was studied in water under different experimental conditions. By contrast with other previously studied β-diketones, the keto-enol interconversion in the ACHE system is a slow process. Under equilibrium conditions, the analysis of the absorbance readings of ACHE aqueous solutions yielded more than 40% of enol content at 25 °C; nevertheless, in aprotic solvents such as dioxane, ACHE is almost completely enolized. In alkaline medium, the enolate ion is the only existing species; the study of the effect of pH on the UV-absorption spectrum of ACHE yielded a value of 9.85 for the overall pKa of ACHE. Under nonequilibrium conditions, the keto-enol tautomerization was studied in water. Several factors affecting the reaction have been investigated, which include H+-catalysis, ionic strength effect, buffer catalysis, deuterium isotope effects, temperature effect, or solvent effects.
- Iglesias, Emilia
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p. 2680 - 2688
(2007/10/03)
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- Asymmetric hydrogenation method of a ketonic compound and derivative
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The present invention relates to a process for the asymmetric hydrogenation of a ketonic compound and derivative. The invention relates to the use of optically active metal complexes as catalysts for the asymmetric hydrogenation of a ketonic compound and derivative. The process for the asymmetric hydrogenation of a ketonic compound and derivative is characterized in that the asymmetric hydrogenation of said compound is carried out in the presence of an effective amount of a metal complex comprising as ligand an optically active diphosphine corresponding to one of the following formulae: STR1
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- Clay catalysis: Storks alkylation and acylation of cyclohexanone without isolation of enamine
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Cyclohexanone and morpholine in the presence of KSF under azeotropic distillation gave 1-morpholinocyclohexane which is alkylated or acylated in situ without isolation of the enamine. The overall yield of these Stork's reactions are better or equivalent to those obtained by isolation of the enamine.
- Hammadi,Villemin
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p. 2901 - 2904
(2007/10/03)
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- Reactions of alkali metal anions. XV. Reaction of ketones with alkali metal anions
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The potassium anions were found to react with ketones to39 yield both alcoholates and enolates. On the basis of the ESR and K NMR measurements the mechanism of this reaction is proposed. According to the proposed mechanism in the first step a ketyl radical is formed which after disproportionation yields an enolate and an alcoholate but only in the case of ketones having hydrogen atom in α-position in respect to carbonyl group.
- Jedlinski,Misioiek,Giowkowski,Janeczek,Wolinska
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p. 3547 - 3558
(2007/10/02)
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- Cardiotonic Agents. 1-Methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and Related Compounds. Synthesis and Activity
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A series of 1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and related compounds were synthesized and evaluated for positive inotropic activity.Most members of this series exerted a dose-dependent increase in myocardial contractility in the dog acute heart failure model, whereas they caused only slight changes in heart rate and blood pressure.Several derivatives, especially those with cyano, acetyl, and ethyl substituents at the 4-position, were more potent than milrinone, which was used as a reference. 4-Acetyl-1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone (MS-857) is one of the most potent positive inotropic agents in this series.
- Kaiho, Tatsuo,San-nohe, Kunio,Kajiya, Seitaro,Suzuki, Tsuneji,Otsuka, Kengo,et al.
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p. 351 - 357
(2007/10/02)
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- Acylation of Ketone Silyl Enol Ethers with Acid Chlorides. Synthesis of 1,3-Diketones
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Trimethylsilyl enol ethers of ketones are acylated by a variety of acid chlorides in the presence of zinc chloride or antimony trichloride.The major product of this reaction is the 1,3-diketone resulting from C-acylation.Some O-acylation is observed in most cases.Yields of 1,3-diketones varied but were usually good to excellent.
- Tirpak, Robin E.,Rathke, Michael W.
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p. 5099 - 5102
(2007/10/02)
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- Acylation of Ketone Silyl Enol Ethers with Acetyl Tetrafluoroborate. A Synthesis of 1,3-Diketones
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Silyl enol ethers, obtained by silylation of ketones, are acylated with acetyl tetrafluoroborate to give 1,3-diketones in reasonable yields.Thetert-butyldimethylsilyl enol ether of cyclohexanone gives a nearly quantitative yield of acetylcyclohexanone, while the trimethylsilyl enol ethers of cyclohexanone and other ketones give moderate yields of the corresponding 1,3-diketones.The regiospecificity of the reaction was studied with the isomeric silyl enol ethers of 2-methylcyclohexanone.
- Kopka, Ihor,Rathke, Michael W.
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p. 3771 - 3773
(2007/10/02)
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- Novel Synthetic Reactions Using Bis(2,2,2-trifluoroethoxy)triphenylphosphorane
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Alkoxy-or (acyloxy)(2,2,2-trifluoroethoxy)triphenylphosphoranes which were prepared in situ by the ligand exchange of bis(2,2,2-trifluoroethoxy)triphenylphosphorane with alcohols or carboxylic acids were found to behave as potential alkylating or acylating reagents for the preparation of a variety of esters, amides, sulfides, and ketones.
- Kubota, Toshio,Miyashita, Satoshi,Kitazume, Tomoya,Ishikawa, Nobuo
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p. 5052 - 5057
(2007/10/02)
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- Novel Synthetic Reactions Using Bis(2,2,2-trifluoroethoxy)diorganosulfuranes
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Alkoxy- or acyloxysulfuranes prepared in situ by the ligand exchange of bis(2,2,2-trifluoroethoxy)diorganosulfuranes with alcohols or carboxylic acids were found to behave as a potential alkylating or acylating reagent for the preparation of unsymmetrical sulfides, ketones, and esters.
- Kitazume, Tomoya,Ishikawa, Nobuo
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p. 2064 - 2066
(2007/10/02)
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