- Kras-G12C inhibitor heterocyclic compounds
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The invention relates to Kras-G12C inhibitor heterocyclic compounds represented by formula I, a preparation method thereof, and application of the Kras-G12C inhibitor heterocyclic compounds in prevention and treatment of tumor diseases such as lung cancer, colorectal cancer and pancreatic cancer. In the preparation process, the compounds of the general formula I are obtained through a series of reactions such as SN2 reaction, protection, coupling reaction, deprotection, condensation reaction and the like.
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Paragraph 0239; 0242-0245
(2021/06/23)
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- Application of fumaric acid monoethyl ester silver salt in preventing novel coronavirus infections
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The invention discloses application of fumaric acid monoethyl ester silver salt in preventing novel coronavirus infections. The application comprises the following steps: adding 1000g of fumaric acidmonoethyl ester into a reaction bottle of 5L, adding 3Kg of pure water, adding 100g of nano silver oxide while stirring, performing a stirring reaction for 9 hours, filtering the reaction liquid to remove impurities, performing vacuum distillation to spin off moisture at 60 DEG C, adding 5Kg of ethanol, performing stirring crystallization for 4.5 hours, performing filtering, collecting a solid, and performing vacuum drying on the obtained solid for 6 hours at 75 DEG C, so as to obtain the fumaric acid monoethyl ester silver salt. The fumaric acid monoethyl ester silver salt is applied to treatment and prevention on various coronaviruses. Experiments show that with a concentration of 500[mu] g/mL, a fumaric acid monoethyl ester silver salt dissolved solution has an inhibition rate of 99.9%upon coronavirus main protease, a corresponding zinc salt dissolved solution and a silver salt dissolved solution of the fumaric acid monoethyl ester silver salt have inhibition rates of 99.9% and 99.7% upon the coronavirus main protease respectively, and the effects are remarkable.
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Paragraph 0022
(2020/06/09)
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- Method for preparing alpha, beta-unsaturated carboxylic acid by reacting alkenyl boron compound with carbon dioxide under catalysis of cuprous halide
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The invention discloses a method for preparing alpha, beta-unsaturated carboxylic acid through a carboxylation reaction of an alkenyl boron compound and carbon dioxide under the catalysis of cuprous halide. According to the method, carbon dioxide is used as a C1 source, the cuprous halide is adopted for catalysis, and alkoxide serves as alkali to react in an organic solvent, so the method is simple and easy to implement, has a wide substrate application range, converts various alkenyl boron compounds such as alkenyl boric acid, alkenyl borate and borate into corresponding alpha, beta-unsaturated carboxylic acid under mild conditions, and has a very high yield. The obtained product alpha, beta-unsaturated carboxylic acid is an important intermediate for preparing fine chemical products suchas perfumes, insecticides and the like.
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Paragraph 0069-0070
(2020/06/17)
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- A comparative study on degradation of complex malathion organophosphate using of Escherichia coli IES-02 and a novel carboxylesterase
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Malathion organophosphates considered as the major constituent of herbicides, pesticides and insecticides. Extensively used in agricultural, horticultures and for numerous household applications contributes to precedence organic pollutants leading antagonistic effects on human health and environment. Therefore detoxification of malathion from contaminated site is of general interest. Simultaneously it is very emerging to isolated novel indigenous microbial strains from contaminated site with a record of pesticide application. In this study Escherichia coli IES-02 isolated from malathion contaminant effluent and the strain showed maximum efficiency in malathion degradation that utilized it as the sole source of carbon. Carboxylesterase (33.0, 30.0, 28.0 kDa) were purified (1685.71 U/mg) from Escherichia coli IES-02 showed significant results in malathion degradation approximately 81% within 20 min as compared with Escherichia coli IES-02 cells within 4 h (99.0 to 95.0%) into monocarboxylic acid and diacid derivatives. The generation time of Escherichia coli was also observed at 60 min with 0.1 ppm, 68 min with 0.5 ppm, 74.5 min with 2.0 ppm and 91.37 min with 50 ppm of malathion. The degradation rate and transformation metabolites were estimated by Gas Chromatography-Mass Spectrometry respectively. Malathion metabolites pathway proposed in this study which revealed the potential application against lethal environmental pollution.
- Ansari, Asma,Iqbal, Sajid,Khan, Moazzam Ali,Qader, Shah Ali Ul,Sattar, Hafsa,Sirajuddin, Sadia
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p. 445 - 455
(2020/01/08)
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- Carboxylation of Alkenyl Boronic Acids and Alkenyl Boronic Acid Pinacol Esters with CO2 Catalyzed by Cuprous Halide
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A cuprous halide catalysed carboxylation of alkenyl boronic acids and alkenyl boronic acid pinacol esters under CO2, affording the corresponding α, β-unsaturated carboxylic acids in good yield, has been developed. The potassium (E)-trifluoro(styryl)borate is also compatible with this reaction. This simple and efficient copper(I) catalytic system showed good functional group tolerance.
- Hong, Junting,Nayal, Onkar S.,Mo, Fanyang
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supporting information
p. 2813 - 2818
(2020/05/16)
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- DRUGS AND COMPOSITIONS FOR OCULAR DELIVERY
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New prodrugs of therapeutically active compounds, including oligomeric prodrugs of ethacrynic acid, and compositions to treat medical disorders, for example glaucoma, a disorder or abnormality related to an increase in intraocular pressure (IOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy. Also a method for the controlled administration of timolol to a patient in need thereof, such as a human, comprising administering a prodrug of timolol in a microparticle in vivo, wherein the timolol prodrug containing microparticle exhibits in vitro drug release kinetics in an aqueous solution at a pH between 6-8 at body temperature of a substantially consistent release of at least 60% timolol itself by molar ratio to the prodrug of timolol or an intermediate metabolite thereof over at least 100 days.
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Page/Page column 160; 161
(2019/07/19)
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- DRUGS AND COMPOSITIONS FOR THE TREATMENT OF OCULAR DISORDERS
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The present invention provides new prodrugs of therapeutically active compounds, including oligomeric prodrugs, and compositions to treat medical disorders, for example glaucoma, a disorder or abnormality related to an increase in intraocular pressure (IOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy.
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Page/Page column 245; 383
(2018/10/19)
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- Preparation method of ethyl 4-(3,4-dimethoxyphenyl)-4-oxo-2-butenoate
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The invention relates to a preparation method of ethyl 4-(3,4-dimethoxyphenyl)-4-oxo-2-butenoate, and belongs to the technical field of chemical reagent synthesis. The preparation method comprises thefollowing steps: firstly performing an esterification reaction on maleic anhydride and ethanol, then performing a transposition reaction to obtain monoethyl fumarate, then performing a reaction on the monoethyl fumarate and sulfoxide chloride to obtain monoethyl monoacyl chloride fumarate, finally performing a reaction on the monoethyl monoacyl chloride fumarate and 1,2-dimethoxybenzene to obtaina target product ethyl 4-(3,4-dimethoxyphenyl)-4-oxo-2-butenoate, and refining to obtain a refined product. By the preparation method, a reaction product in each step is relatively high in yield andpurity, the finally prepared refined product is also high in yield and purity, and raw materials are simple, easy to obtain and low in cost; in addition, the preparation method is easy to operate, impurities in the product are easily separated and removed, and the refined product has the purity of 99% or above and fully meets requirements of customers for a medical purpose.
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Paragraph 0027; 0029; 0038; 0041; 0042; 0043
(2018/11/03)
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- Synthesis of α,β-unsaturated esters of perfluoropolyalkylethers (PFPAEs) based on hexafluoropropylene oxide units for photopolymerization
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α,β-unsaturated esters are usually synthesized for polymer applications. However, the addition of maleate (cis-configuration) to a fluorinated moiety is challenging due to its potential isomerization during esterification. Various synthetic routes were attempted and led to very low conversion or side-products. The immiscibility of both reagents combined with an easy isomerization or attack on the double bond were potential explanations. In this paper, the synthesis of maleates oligo(hexafluoropropylene oxide) is reported by Steglich esterification and the reaction conditions are discussed depending on the molecular weight of the fluorinated moieties. After UV-curing, hydrophobic polymers were obtained by copolymerization with vinyl ethers by electron acceptor-donor systems.
- Bonneaud, Céline,Decostanzi, Mélanie,Burgess, Julia,Trusiano, Giuseppe,Burgess, Trevor,Bongiovanni, Roberta,Joly-Duhamel, Christine,Friesen, Chadron M.
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p. 32664 - 32671
(2018/10/15)
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- Synthesis, DFT and antimicrobial activity assays in vitro for novel cis/trans-but-2-enedioic acid esters
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Six novel cis/trans-but-2-enedioic acid esters had been synthesized to discover the new bioactive molecules that could kill food-related bacteria and fungi. Their structures were analyzed by melting point, LC-MS, 1H NMR and 13C NMR. 4-(Methoxycarbonyl) phenyl ethyl fumarate (6b) was also characterized by single-crystal X-ray diffraction. Their antimicrobial activities were evaluated in vitro by measuring the minimal inhibitory concentration (MIC). Compared with the single monomethyl fumarate and methyl 4-hydroxybenzoate, these compounds had stronger antimicrobial activity against all the eight microorganisms. Among the antibacterial and antifungal compounds, 4-(methoxycarbonyl) phenyl methyl fumarate (6a) showed the best antimicrobial activity. The electronic properties of these compounds were calculated by the density functional theory (DFT) method with 6-31G (d, p) basis set. DFT studies indicated that molecular electrostatic potential (MEP) map, ELUMO, energy gap, electronegativity and electrophilicity index could be helpful to understand the various antimicrobial activities among these compounds. The antimicrobial activity of compound 6a was evaluated in vitro against Salmonella choleraesuis subsp. choleraesuis, Lactococcus lactis subsp. lactis and Saccharomyces cerevisiae by time-kill, and it was found that compound 6a exhibited significant microbiocidal activity against the three microorganisms.
- Ma, Yan-Long,Zhou, Ru-Jin,Zeng, Xing-Ye,An, Ya-Xiong,Qiu, Song-Shan,Nie, Li-Jun
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p. 226 - 234
(2014/03/21)
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- A protocol for accessing the β-azidation of α,β-unsaturated carboxylic acids
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This contribution reports the preparation and use of a new immobilized catalyst, PS-DABCOF (9), which has been specifically designed to access for the first time the efficient β-azidation of α,β-unsaturated carboxylic acids.
- Angelini, Tommaso,Bonollo, Simona,Lanari, Daniela,Pizzo, Ferdinando,Vaccaro, Luigi
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supporting information
p. 4610 - 4613
(2012/10/30)
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- Ring-opening of cyclic anhydrides using ionic liquids
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Four novel Bronsted acidic ionic liquids with two different acid sites on the imidazolium cations were synthesised and employed as catalysts and solvents for the ring-opening of cyclic anhydrides to synthesise half-esters. The results showed that these novel Bronsted acidic ionic liquids were efficient and recyclable. Good yields, short reaction times and mild reaction conditions were achieved.
- Jiang, Dong,Wang, Yuan Yuan,Xu, Yan Nan,Dai, Li Yi
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experimental part
p. 167 - 169
(2009/10/15)
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- Organocatalysis in conjugate amine additions. Synthesis of β-amino acid derivatives
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Conjugate addition of O-protected hydroxylamines to pyrazole-derived enoates proceeds with high efficiency and enantioselectivity when chiral thioureas are used as activators. A wide variety of substrates undergo conjugate amine addition providing access to enantioenriched β-amino acid derivatives. Structural requirements for the optimal thiourea catalyst have been established, and the results suggest that it operates as a bifunctional catalyst. Copyright
- Sibi, Mukund P.,Itoh, Kennosuke
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p. 8064 - 8065
(2008/02/09)
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- Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10
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Aza-peptide Michael acceptors are a novel class of inhibitors that are potent and specific for caspases-2, -3, -6, -7, -8, -9, and -10. The second-order rate constants are in the order of 106 M-1 s-1. The aza-peptide Michael acceptor inhibitor 18t (Cbz-Asp-Glu-Val-AAsp-trans-CH=CH-CON(CH2-1-Naphth)2 is the most potent compound and it inhibits caspase-3 with a k2 value of 5620000 M-1 s-1. The inhibitor 18t is 13700, 190, 6.4, 594, 37500, and 173-fold more selective for caspase-3 over caspases-2, -6, -7, -8, -9, and -10, respectively. Aza-peptide Michael acceptors designed with caspase specific sequences are selective and do not show any cross reactivity with clan CA cysteine proteases such as papain, cathepsin B, and calpains. High-resolution crystal structures of caspase-3 and caspase-8 in complex with aza-peptide Michael acceptor inhibitors demonstrate the nucleophilic attack on C2 and provide insight into the selectivity and potency of the inhibitors with respect to the P1′ moiety.
- Ekici, ?zlem Do?an,Li, Zhao Zhao,Campbell, Amy J.,James, Karen Ellis,Asgian, Juliana L.,Mikolajczyk, Jowita,Salvesen, Guy S.,Ganesan, Rajkumar,Jelakovic, Stjepan,Grütter, Markus G.,Powers, James C.
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p. 5728 - 5749
(2008/04/18)
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- PROPENOYL HYDRAZIDES
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The present disclosure provides compositions for inhibiting proteases, methods for synthesizing the compositions, and methods of using the disclosed protease inhibitors. Aspects of the disclosure include a peptidyl propenoyl hydrazide compositions that inhibit proteases, for example cysteine proteases, either in vivoor in vitro.
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Page/Page column 34
(2008/06/13)
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- Synthesis of 1,3,5-trisubstituted hydantoins by regiospecific domino condensation/aza-Michael/O→N acyl migration of carbodiimides with activated α,β-unsaturated carboxylic acids
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(Chemical Equation Presented) Carbodiimides and suitably activated α,β-unsaturated carboxylic acids react effectively to afford a vast array of 1,3,5-trisubstituted hydantoins by means of a regiospecific domino condensation/aza-Michael/N→O acyl migration. The reaction works well in very mild conditions (20°C, dichloromethane) with fumaric acid derivatives bearing an electron-withdrawing group in the β position. Good results have been obtained also with less activated substrates bearing only one electron-withdrawing group in the β position, using more polar solvents (acetonitrile, DMF), and in the presence of a base (2,4,6-trimethylpyridine). Reactions with asymmetric carbodiimides are generally highly chemo- and regioselective, giving rise to the formation of a single regioisomeric hydantoin. However, asymmetric carbodiimides bearing one alkyl group and one aryl group can produce variable amounts of N-acylurea byproducts. The latter could be easily recovered and transformed into the corresponding hydantoins. A detailed study of the influence of key reaction parameters such as solvent, base, and structure of the reactants on the reaction outcome and mechanism is presented. This methodology is particularly convenient for the synthesis of trifluoromethyl-substituted hydantoins, which could be interesting as bioactive compounds in medicinal chemistry, as well as precursors of the corresponding α-amino acids.
- Volonterio, Alessandro,De Arellano, Carmen Ramirez,Zanda, Matteo
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p. 2161 - 2170
(2007/10/03)
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- Ring opening of cyclic anhydrides: Synthesis of achiral half-esters using Lewis acids
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A rapid and high yield preparation of half-esters from cyclic anhydrides using alcohols and Lewis acids is described.
- Sabitha, Gowravaram,Srividya,Yadav
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p. 4015 - 4018
(2007/10/03)
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- Macrocyclic ethers by free radical cyclizations
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Tin hydride reduction of ω-iodo-polyoxaalkyl acrylates 1 using syringe pump addition of both reactants to a solution of AIBN in benzene at 80°C afforded the corresponding cyclic polyethers in excellent yields.
- Philippon, Annie,Tao, Jingchao,Tetard, David,Degueil-Castaing, Marie,Maillard, Bernard
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p. 2651 - 2682
(2007/10/03)
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- Enzymatic selective transformations of diethyl fumarate
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Candida antarctica lipase selectively catalyses transformations of diethyl fumarate in organic solvents. A range of nitrogen nucleophiles, including ammonia, can be successfully used in these enzymatic reactions, monoamides and monohydrazides being obtained in high to moderate yields. In contrast, diethyl maleate is not an adequate substrate for this enzyme.
- Quiros, Margarita,Astorga, Covadonga,Rebolledo, Francisca,Gotor, Vicente
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p. 7715 - 7720
(2007/10/02)
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- Iron (III) perchlorate: A reagent for trans-esterification
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Iron (III) perchlorate has successfully been used for the trans-esterification of ethyl acetate with alcohols and acids.
- Kumar, Baldev,Kumar, Harish,Parmar, Anupama
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p. 292 - 293
(2007/10/02)
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- Pyridazinone derivatives
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A pyridazinone compound represented by the general formula STR1 wherein Ar is STR2 in which R1, R2 and R3 may be identical or different, and each represents a hydrogen atom, a lower alkyl group, a trifluoromethyl group, a halogen atom, a cyano group or a nitro group, and R4 represents a hydrogen atom, a lower alkoxy group, or a lower alkyl group substituted by a lower alkoxy group or a carbamoyl group, and C* is an asymmetric carbon atom, or a salt thereof. This compound is useful for the treatment of diseases of the circulatory system.
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- Antihypertensive pyridazinone aminoisopropanol derivatives
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A pyridazinone derivative represented by the following general formula STR1 wherein R1 represents a hydrogen atom or a methyl group, either one of R2, R3 and R4 represents a hydrogen atom and the remaining two of them represent a lower alkyl group, a trifluoromethyl group, a halogen atom, a cyano group or a nitro group, and a salt thereof. The compounds are useful as antihypertensive agents.
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- High- and Low-Potential Flavin Mimics. 3. 3,7,10-Trimethyl-(1H,3H,5H,7H,9H,10H)-pyrimidopteridine-2,4,6,8-tetrone-Mediated Reduction of Carbon-Carbon Double Bond α-β to an Acyl Function
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The reduction of the carbon-carbon double bond of maleimide (MI), N-methylmaleimide (NMM), ethyl fumarate, diethyl fumarate, diethyl maleate, fumaric acid, and maleic acid was investigated by employing the low redox potential flavin mimic 3,7,10-trimethyl-(1H,3H,5H,7H,9H,10H)-pyrimidopteridine-2,4,6,8-tetrone (PPTH2) as the reductant.The reaction of these substrates with PPTH2 to produce PPTox and the corresponding succinimide or succinate consists of three processes.The first process occurs on mixing and pertains to the formation of a mixture of N(1)- and C(4a)-substrate adducts of PPTH2.The other two processes, which are kinetically distinguishable, pertain to the breakdown of each of these adducts to PPTox and the reduced substrate.Breakdown of the C(4a)-adduct is catalyzed by hydroxide and is independent of substrate concentration.Hydroxide catalysis is proposed to represent a concerted process whereby the hydroxide abstracts the N(5)-proton while the anionic reduced substrate is departing (Bronsted β approaching 1.0).Breakdown of the N(1)-adduct to the observed products is substrate-dependent pertaining to the rate-determining formation of the N(9),C(4a)-diadduct.In a fast step, base-catalyzed elimination from the C(4a)-position of the latter provides the reduced substrate anion and the N(9)-monosubstrate adduct of PPTox.Rapid dissociation of the N(9)-adduct then provides PPTox.It is concluded that the reduction of a carbon-carbon double bond to an acyl function by the low-potential flavin mimic proceeds via C(4a)-adducts.This conclusion and the principle of microreversibility infers that enzyme-bound flavins of high potential, as in dehydrogenating flavoenzymes, may oxidize succinates to fumarates via C(4a)-adducts.
- Skibo, Edward B.,Bruice, Thomas C.
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p. 1650 - 1659
(2007/10/02)
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- Process for the preparation of fumaric acid monoesters
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Fumaric acid monoesters can be prepared by introducing a hydroxyl compound at a rate corresponding to the progress of the reaction into a solution or a melt of maleic anhydride, which may optionally be substituted, if appropriate in the presence of a cis-trans catalyst. New fumaric acid monoesters can be formed by the process.
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- 277. Structure and Chemistry of Malonylmethyl- and Succinyl-Radicals. The Search for Homolytic 1,2-Rearrangements
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Malonylmethyl radical I and its thioester analogue II were generated by standard photolytic and thermolytic methods from perester and bromo precursors.The structures of I and II were examined by ESR spectroscopy and found to exist in preferred conformations.However, no indication for their rearrangement by 1,2-shift of either an ethoxycarboxyl or (ethylthio)carbonyl group to the corresponding succinyl radicals III and IV, respectively, was found at temperatures below -40 deg C.At higher temperatures of up to 140 deg C, the search for malonylmethyl -> succinyl rearrangement was examined by thorough-product analysis of the perester decomposition.There is evidence for the rearrangement of the radical I to III by photolysis and of the radical II to IV by thermolysis at 130 deg C in chlorobenzene to only a small extent.
- Aeberhard, Urs,Keese, Reinhart,Stamm, Erich,Voegeli, Ulrich-Christian,Lau, Willy,Kochi, Jay Kazuo
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p. 2740 - 2759
(2007/10/02)
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