- Five-membered heterocyclic oxo carboxylic acid compound and medical application thereof
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The invention relates to a five-membered heterocyclic oxo carboxylic acid compound and a medical application thereof. Specifically, the invention relates to a compound, a pharmaceutical salt, a prodrug, a hydrate, a solvate or a crystal form as shown in a formula (I), and also relates to a preparation method of the compound, a pharmaceutical composition containing the compound and an application of the pharmaceutical composition as a secretion regulator of interferon type I, especially as an STING agonist in preparation of medicines for preventing and/or treating I-type interferon related diseases.
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Paragraph 0378-0382
(2021/05/01)
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- DIPHENYLAMINO-METHYLENE MALONONITRILE BASED COMPOUNDS AS FLUORESCENCE PROBES
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The present invention provides compounds of formula (I) and formula (II): or a pharmaceutically acceptable salt or a stereoisomer thereof; wherein, ring A and ring B have the meanings given in the specification. The compounds of the present disclosure are useful as fluorescence probe in detecting tubulin in a sample and therefore useful for the diagnosis of tubulin and its associated diseases like cancer in a subject.
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Page/Page column 19-20
(2020/03/23)
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- Pyrazoles: 'one-pot' synthesis from arenes and carboxylic acids
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A rapid and efficient method for 'one-pot' synthesis of pyrazoles from (hetero)arenes and carboxylic acids via successive formation of ketones and β-diketones followed by heterocyclization with hydrazine has been developed. The utility of the RCOOH/TfOH/TFAA acylation system for intermediate production of ketones and 1,3-diketones is a key feature of this approach. The preliminary evaluation of the anticancer activity of the synthesized pyrazoles is performed.
- Gong, Ming,Kim, Jung Keun,Kovalev, Vladimir V.,Kovaleva, Olga V.,Shokova, Elvira A.,Tafeenko, Viktor A.,Wu, Yangjie
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supporting information
p. 5625 - 5638
(2020/08/21)
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- "one-Pot" Synthesis of γ-Pyrones from Aromatic Ketones/Heteroarenes and Carboxylic Acids
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Despite the various attractive properties of γ-pyrones, there are still some deficiencies in their synthetic approaches such as lower atom economy, multistep processes, and prefunctionalization of the reagents. In this work, an efficient and simple (CF3CO
- Sun, Xiangyu,Gong, Ming,Huang, Mengmeng,Li, Yabo,Kim, Jung Keun,Kovalev, Vladimir,Shokova, Elvira,Wu, Yangjie
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p. 15051 - 15061
(2020/12/02)
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- Metal-Free Aerobic Oxidative Selective C-C Bond Cleavage in Heteroaryl-Containing Primary and Secondary Alcohols
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A transition-metal-free aerobic oxidative selective C-C bond-cleavage reaction in primary and secondary heteroaryl alcohols is reported. This reaction was highly efficient and tolerated various heteroaryl alcohols, generating a carboxylic acid derivative and a neutral heteroaromatic compound. Experimental studies combined with density functional theory calculations revealed the mechanism underlying the selective C-C bond cleavage. This strategy also provides an alternative simple approach to carboxylation reaction.
- Xia, Anjie,Qi, Xueyu,Mao, Xin,Wu, Xiaoai,Yang, Xin,Zhang, Rong,Xiang, Zhiyu,Lian, Zhong,Chen, Yingchun,Yang, Shengyong
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supporting information
(2019/05/07)
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- Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model
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FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV4-11 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML.
- Heng, Hao,Wang, Zhijie,Li, Hongmei,Huang, Yatian,Lan, Qingyuan,Guo, Xiaoxing,Zhang, Liang,Zhi, Yanle,Cai, Jiongheng,Qin, Tianren,Xiang, Li,Wang, Shuxian,Chen, Yadong,Lu, Tao,Lu, Shuai
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p. 248 - 267
(2019/05/21)
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- Compounds and use thereof in anti-AML drugs
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The present invention relates to the field of medicinal chemistry, discloses compounds and use thereof in anti-AML drugs, and specifically relates to imidazole ring-substituted thiophenic compounds, preparation method thereof, pharmaceutical compositions containing the compounds, and medical use of the compounds, particularly use of the compounds as an ITD mutant selective inhibitor of FMS-like tyrosine kinase 3.
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Paragraph 0152; 0191; 0192; 0193
(2018/11/04)
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- BENZOBIS (THIADIAZOLE) DERIVATIVE AND ORGANIC ELECTRONICS DEVICE
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PROBLEM TO BE SOLVED: To provide a benzobis (thiadiazole) derivative that is easy and simple to synthesize and is excellent in electronic mobility (field-effect mobility). SOLUTION: The present invention provides a benzobis (thiadiazole) derivative represented by general formula (1) (where R1 and R2 each represent a predetermined group). SELECTED DRAWING: None COPYRIGHT: (C)2016,JPO&INPIT
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Paragraph 0211-0213
(2018/10/16)
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- Direct Transformation of Ethylarenes into Primary Aromatic Amides with N -Bromosuccinimide and I2-Aqueous NH3
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A variety of ethylarenes were converted into the corresponding primary aromatic amides in good yields via treatment with N-bromosuccinimide in the presence of a catalytic amount of 2,2′-azobis(isobutyronitrile) in a mixture of ethyl acetate and water, acetonitrile and water, or chloroform and water, followed by reaction with molecular iodine and aq NH3 in one pot. It was found that aryl α-bromomethyl ketones and/or aryl methyl ketones were formed at the first reaction step and their iodoform-type reaction occurred at the second reaction step to provide primary aromatic amides. The present reaction is a useful and practical transition-metal-free method for the preparation of primary aromatic amides from ethylarenes. (Chemical Equation Presented).
- Shimokawa, Shohei,Kawagoe, Yuhsuke,Moriyama, Katsuhiko,Togo, Hideo
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supporting information
p. 784 - 787
(2016/03/01)
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- P-tert-Butylcalix[8]arene catalysed synthesis of 3,5-dinitrothiophene scaffolds: Antiproliferative effect of some representative compounds on selective anticancer cell lines
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A new efficient protocol for the synthesis of 3,5-dinitrothiophene scaffolds was developed by using simple p-tert-butylcalix[8]arene in aqueous medium. Biological activities of some representative compounds were also studied to inhibit the cell growth on selective anticancer cell lines.
- Sarkar, Piyali,Maiti, Samares,Ghosh, Krishnendu,Sengupta, Sumita,Butcher, Ray J.,Mukhopadhyay, Chhanda
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supporting information
p. 996 - 1001
(2014/02/14)
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- P-tert-Butylcalix[8]arene catalysed synthesis of 3,5-dinitrothiophene scaffolds: Antiproliferative effect of some representative compounds on selective anticancer cell lines
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A new efficient protocol for the synthesis of 3,5-dinitrothiophene scaffolds was developed by using simple p-tert-butylcalix[8]arene in aqueous medium. Biological activities of some representative compounds were also studied to inhibit the cell growth on selective anticancer cell lines.
- Sarkar, Piyali,Maiti, Samares,Ghosh, Krishnendu,Bandyopadhyay, Sumita Sengupta,Butcher, Ray J.,Mukhopadhyay, Chhanda
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supporting information
p. 996 - 1001
(2015/02/19)
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- Metal and H2O2 free aerobic oxidative aromatic halogenation with [RNH3+] [NO3-]/HX and [BMIM(SO3H)][NO3)x(X)y] (X = Br, Cl) as multifunctional ionic liquids
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Novel multifunctional ionic liquids (ILs) are generated by addition of HBr or HCl to alkylammonium nitrates ([RNH3+] [NO 3-]) and to 3-methyl-1-(butyl-4-sulfonyl)imidazolium nitrate ([BMIM(SO3H)][NO3]). The resulting [RNH 3+] [NO3-]/HX and mono (3-methyl-1-(butyl-4-sulfonyl)imidazolium) monohalogenide mononitrate ([BMIM(SO3H)][NO3)x(X)y] (X = Br, Cl)) systems act as solvent and promoter for aerobic oxidative halogenation of arenes under mild conditions in high yields that can be repeated over several cycles.
- Prebil, Rok,Laali, Kenneth K.,Stavber, Stojan
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supporting information
p. 2108 - 2111
(2013/06/05)
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- A novel method for the bromination of thiophenes
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A novel, fast and convenient method for the bromination of thiophenes and oligothiophenes with N-bromosuccinimide (NBS) using ultrasonic irradiation is elaborated. The yield of bromothiophenes strongly depends on the initial thiophene structure and nature of the solvent.
- Arsenyan, Pavel,Paegle, Edgars,Belyakov, Sergey
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scheme or table
p. 205 - 208
(2010/03/24)
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- Studies with enaminones and enaminonitriles: synthesis of 3-aroyl and 3-heteroaroyl-pyrazolo-[1,5-a]pyrimidines
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The reaction of electron rich aromatics with cyanoacetic acid and acetic anhydride afforded 3-oxoalkanenitriles. Indium trichloride was used as a Lewis acid catalyst when the aromatic ring was not?sufficiently reactive. The synthesized 3-oxoalkanenitriles were subsequently condensed with dimethylformamide dimethylacetal (DMFDMA) to yield enaminones that reacted readily with hydrazine hydrate to yield 4-aroylpyrazole-3-amines. The 4-aroylpyrazole-3-amines were condensed with enaminones to yield 3-aroylpyrazolo[1,5-a]pyrimidines.
- Khalil, Khaled D.,Al-Matar, Hamad M.,Al-Dorri, Doa'a M.,Elnagdi, Mohamed H.
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experimental part
p. 9421 - 9427
(2009/12/28)
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- Synthesis of benzo[c] and naphtho[c]heterocycle diesters and dinitriles via homoelongation
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(Chemical Equation Presented) Syntheses of benzo[c] and naphtho[c]heterocycle diesters and dinitriles were achieved via our newly developed iterative elongation protocol. The photophysical and electrochemical properties of these conjugated systems are explored.
- Hsu, Dong-Tsou,Lin, Chih-Hsiu
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supporting information; experimental part
p. 9180 - 9187
(2010/03/02)
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- Unexpectedly high activity of Zn(OTf)2·6H2O in catalytic Friedel-Crafts acylation reaction
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Zn(OTf)2·6H2O was used to promote Friedel-Crafts acylation of aromatics. The work describes the high activity and efficiency of Zn(OTf)2·6H2O in acylation of aromatics, and the catalyst has surpassed most metal triflates in dispensing when dried at high temperature under vacuum before use. Copyright Taylor & Francis Group, LLC.
- He, Fei,Wu, Huayue,Chen, Jiuxi,Su, Weike
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p. 255 - 264
(2008/03/17)
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- Synthesis and antibacterial activity of N-[2-(5-bromothiophen-2-yl)-2- oxoethyl] and N-[(2-5-bromothiophen-2-yl)-2-oximinoethyl] derivatives of piperazinyl quinolones
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A series of N-[2-(5-bromothiophen-2-yl)-2-oxoethyl] and N-[2-(5-bromothiophen-2-yl)-2-oximinoethyl]derivatives of piperazinyl quinolones were synthesized and evaluated for antimicrobial activity against Gram-positive and Gram-negative microorganisms. Some of these derivatives exhibit comparable or better activity against Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis, than ciprofloxacin, norfloxacin and enoxacine as reference drugs.
- Foroumadi, Alireza,Emami, Saeed,Mehni, Massood,Moshafi, Mohammad Hassan,Shafiee, Abbas
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p. 4536 - 4539
(2007/10/03)
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- Ytterbium(III) trifluoromethanesulfonate catalysed Friedel-Crafts acylation of substituted thiophenes
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Ytterbium(III) trifluoromethanesulfonate [Yb(OTf)3] has been used to catalyse Friedel-Crafts acylation of substituted thiophenes in different solvents to produce several intermediates of pharmaceuticals and pesticides with good yields. The amount of catalysis was discussed and Yb(OTf)3 could be reused without loss of activity.
- Su, Weike,Jin, Can
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p. 694 - 695
(2007/10/03)
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- Halogenation of aromatic methyl ketones using oxone and sodium halide
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Aromatic methyl ketones undergo α-halogenation on treatment with sodium halide in the presence of oxone in aqueous methanol. However, electron-rich hetero aromatic methyl ketones afford ring bromination products preferentially.
- Kim,Koo,Song,Lee
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p. 3627 - 3632
(2007/10/03)
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- A general and simple method for the synthesis of star-shaped thiophene derivatives
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One pot synthesis of 1, 3, 5-tris(thienyl)benzene derivatives via tetrachlorosilane mediated trimerization reaction is described.
- Kotha, Sambasivarao,Chakraborty, Kakali,Brahmachary, Enugurthi
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p. 1621 - 1623
(2007/10/03)
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- Facile synthesis of 5-substituted 2-acetylthiophenes
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5-Substituted 2-(α-alkoxyimino)ethylthiophenes 4-8 are obtained by the reaction of 2-(α-alkoxyimino)ethylthiophenes 3 and electrophilic reagents. Hydrolysis of thiophenes 4-8 produces 5-substituted 2-acetylthiophenes 9-13, respectively. Compounds 3 are easily obtained either by the reaction of 2-acetylthiophene (1) and an O-alkylhydroxylamine or by oxidation of 1 followed by O-alkylation.
- Goda,Sato,Ihara,Hirayama
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p. 849 - 851
(2007/10/02)
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- Thienopyridine derivatives useful in treating gastric ulcers
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A compound of the formula: STR1 (wherein R1 is hydrogen, C1 -C5 alkyl, C1 -C5 alkoxy, C1 -C5 alkoxycarbonyl, or trifluoromethyl; R2 is hydrogen, C1 -C5 alkoxycarbonyl, C6 -C12 aryloxycarbonyl, C1 -C5 alkanoyloxy-C1 -C5 alkyl, C1 -C5 alkoxycarbonyloxy-C1 -C5 alkyl, C1 -C5 acylamino-C1 -C5 alkyl, 2-hydroxy-1-C2 -C5 alkenyl, phthalimido-C1 -C5 alkyl, halogeno-C1 -C5 alkoxycarbonyl-C1 -C5 alkyl, hydroxy-C1 -C5 alkyl, C1 -C5 alkylthio-C1 -C5 alkyl, or C1 -C5 alkylsulfinyl-C1 -C5 alkyl; STR2 m is an integer of 0 or 1; R3 and R4 each is hydrogen, halogen, cyano, C1 -C5 alkyl, amino, C1 -C5 alkoxy, C6 -C12 aryl-C1 -C5 alkoxy, C1 -C5 alkoxycarbonyl, fluoro-C1 -C5 alkoxy, C1 -C5 alkanoylamino, or carbamoyl) or its salt, being useful as antiulcer agents, is provided.
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- Thiophene derivatives and methods for producing the same
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Novel compounds, 2-(α-alkoxyimino)ethylthiophenes are susceptible to electrophilic substitution reactions, and the acetylation, nitration, sulfonation and halogenation of the compounds provide 5-acetyl-2-(α-alkoxyimino)ethylthiophenes, 5-nitro-2-(α-alkoxyimino)ethylthiophenes, 5-(α-alkoxyimino)ethyl-2-thiophenesulfonic acid and 5-halo-2-(α-alkoxyimino)ethylthiophenes, respectively. The hydrolysis of 5-acetyl-2-(α-alkoxyimino)ethylthiophenes readily provides a known compound, 2,5-diacetylthiophene which is an important intermediate for the production of medicines, whereas the haloform reaction provides novel compounds, 5-(α-alkoxyimino)ethyl-2-thiophenecarboxylic acids, the hydrolysis of which compounds readily provides a known compound, 5-acetyl-2-thiophenecarboxylic acids, an important intermediate for the production of medicines. The hydrolysis of 5-(α-alkoxyimino)ethyl-2-thiophenesulfonic acids and their salts provide novel 5-acetyl-2-thiophenesulfonic acid and its salts, respectively. Novel compounds, 2-(α-alkoxyimino)ethylthiophenes are obtained either by 0-alkylation of 2-acetylthiophene oxime or by directly reacting 2-acetylthiophene with an 0-alkylhydroxylamine.
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- Charge Density - Activation Energy Correlations in Bromination of Thiophenes by N-Bromosuccinimide in Solution
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The activation energies for N-bromosuccinimide bromination of several thiophene derivatives in 80percent (v/v) aqueous acetic acid have been determined and discussed in the light of electron densities at the reaction site.The effect of substituents at different positions of thiophene ring has been investigated quantitatively by the actual calculation of total (? + ?) charge densities at various positions of the substituted thiophenes.
- Rajaraman, Lalitha,Nanjan, M. J.
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p. 538 - 539
(2007/10/02)
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- Kinetics of the Detritiation of a Series of 4- and 5-Substituted 2-(acetyl)thiophenes
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A series of 4- and 5-substituted 2-(acetyl)thiophenes have been prepared and the kinetics of the hydroxide-catalysed detritiation studied at 25.0 deg C.The second-order detritiation rate constants parallel those observed for the corresponding meta- and para-substituted acetophenones but as the reaction constant ρ is higher (1.61) the range of reactivity is much wider than that witnessed for the acetophenones.
- Jones, John R.,Pearson, Gerd M.,Spinelli, Domenico,Consiglio, Giovanni,Arnone, Caterina
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p. 557 - 558
(2007/10/02)
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- Synthesis of 2,6-Disubstituted Pyridines, Polypyridinyls, and Annulated Pyridines
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1,5-Enediones containing a variety of substituents in the 1,5-positions are formed in good yields by the reaction of methyl ketone enolates, generated with potassium tert-butoxide, with α-oxoketene dithioacetals, the latter being prepared from alkyl, cycloalkyl, aryl, or heteryl methyl ketones, NaH, CS2, and CH3I.Ring closure of the 1,5-enediones with NH4OAc gave 2,6-disubstituted 4-(methylthio)pyridines in good to excellent yields.This procedure is particularly suited for the synthesis of 2,6-diheterylpyridines and provides a simple synthesis of terpyridinyl and other oligopyridines.The methylthio groups in the α-oxoketene dithioacetals may be oxidized to the mono- and disulfoxides with m-chloroperbenzoic acid, but with excess peracid, in addition to oxidation to the disulfone, epoxidation of the double bond also occurs.The pyridine 4-methylthio substituent may also be oxidized to the sulfoxide and to the sulfone, and the latter may be displaced with cyanide ion to form the corresponding 4-carbonitrile.
- Potts, Kevin T.,Cipullo, Michael J.,Ralli, Philip,Theodoridis, George
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p. 3027 - 3038
(2007/10/02)
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- Bromothiophene Reactions. I. Friedel-Crafts Acylation
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Friedel-Crafts acylation of 2,5-dibromo- and 2,3,5-tribromothiophenes with different acyl chlorides and anhydrous aluminium trichloride has been studied.The reaction afforded a mixture of acyl derivatives and tetrabromothiophene.The results obtained suggest a mechanism which involves the formation of bromine cations in the reaction medium.Several products obtained in this reaction are described.
- Agua, M. J. del,Alvarez-Insua, A. S.,Conde, S.
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p. 1345 - 1347
(2007/10/02)
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