- ION CHANNEL ANTAGONISTS/BLOCKERS AND USES THEREOF
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Provided are ion channel antagonists/blockers and uses thereof. Specifically, it provides the compounds of formula (I) or pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs, preparation method therefor and application thereof. Definition of each group in the formula can be found in the specification for details. Provided is also pharmaceutical composition useful for treatment of heart disease and other ion channel related diseases.
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Page/Page column 22; 25; 66; 67; 85
(2021/06/22)
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- PYRIDONE-PYRIMIDINE DERIVATIVE ACTING AS KRASG12C MUTEIN INHIBITOR
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Provided are a class of KRAS G12C mutein inhibitors, which relate in particular to a compound represented by formula (I), an isomer thereof, and a pharmaceutically acceptable salt thereof.
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Paragraph 0278
(2020/12/07)
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- Iodine(III)-Catalyzed Electrophilic Nitration of Phenols via Non-Br?nsted Acidic NO2+ Generation
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The first catalytic procedure for the electrophilic nitration of phenols was developed using iodosylbenzene as an organocatalyst based on iodine(III) and aluminum nitrate as a nitro group source. This atom-economic protocol occurs under mild, non-Br?nsted acidic and open-flask reaction conditions with a broad functional-group tolerance including several heterocycles. Density functional theory (DFT) calculations at the (SMD:MeCN)Mo8-HX/(LANLo8+f,6-311+G) level indicated that the reaction proceeds through a cationic pathway that efficiently generates the NO2+ ion, which is the nitrating species under neutral conditions.
- Juárez-Ornelas, Kevin A.,Jiménez-Halla, J. Oscar C.,Kato, Terumasa,Solorio-Alvarado, César R.,Maruoka, Keiji
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supporting information
p. 1315 - 1319
(2019/03/07)
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- Method for catalyzing selective nitrification of 2-methoxynaphthalene by utilizing zeolite molecular sieve
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The invention discloses a method for catalyzing selective nitrification of 2-methoxynaphthalene by utilizing a zeolite molecular sieve. The method comprises the following steps: S1, dissolving 6 mmolof 2-methoxynaphthalene in 10 mL of dichloromethane, adding 5 mL of acetic anhydride and 0.3-1.1 g of the zeolite molecular sieve catalyst, slowly adding 2 mmol of aluminum nitrate in a stirring state, and carrying out a water bath stirring reaction at 25 DEG C for 12 h; S2, hydrolyzing acetic anhydride at 40 DEG C for 1 h after the reaction is finished; S3, extracting, washing and drying the reacted solution obtained in step S2 after THE hydrolysis is completed; and S4, performing rotary evaporation on the dichloromethane in a solution product obtained in step S3 to achieve evaporative crystallization in order to obtain a crude extract, wherein the raw material conversion rate reaches 85.20-100%, the yield reaches 69.88-82.02%, and the isomerization rate reaches 1.56-6.09. The zeolite molecular sieve is used for catalyzing the selective nitration reaction of 2-methoxynaphthalene for the first time, the catalytic effect of the ZSM-5 zeolite molecular sieve is the most remarkable, and when the weight of the ZSM-5 catalyst is 0.9 g, the substrate conversion rate is high and reaches 93.98%, the yield is 77.09%, and the isomerization rate reaches 6.05%.
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Paragraph 0038-0088
(2019/12/29)
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- Direct nitration method of electron-enriched aromatic hydrocarbons
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The invention discloses a direct nitration method of electron-enriched aromatic hydrocarbons, and belongs to the field of organic synthesis. The direct nitration method is a novel green free radical nitration method; aromatic hydrocarbons are taken as raw materials, acetonitrile, dichloromethane, chloroform, or acetone is taken as a reaction solvent, at room temperature conditions, the raw materials and green nitration reagent tert-butyl nitrite (TBN) are subjected to free radical nitration so as to obtain nitro-aromatic compounds. According to the direct nitration method, no metal is adoptedin reaction, tert-butyl nitrite is directly adopted in nitration reaction. Electron-donating groups such as OMe are introduced, the electron density of aromatic compounds is increased, the nitration reaction possibility is increased. The using amount of tert-butyl nitrite is reduced; only a product and tert-butyl alcohol are generated, environment pollution is reduced. The direct nitration methodis promising in application prospect in the field of nitro-aromatic compound synthesis, green nitration is realized, and a novel idea is provided for large-scale industrialized nitro-aromatic compoundproduction.
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Paragraph 0087-0089
(2018/10/02)
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- Transetherification of 2,4-dimethoxynitrobenzene by aromatic nucleophilic substitution
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In view of the few reports concerning aromatic nucleophilic substitution reactions featuring an alkoxy group as a leaving group, the aromatic nucleophilic substitution of 2,4-dimethoxy-nitrobenzene was investigated with a bulky t-butoxide nucleophile under microwave irradiation. The transetherification of 2,4-dimethoxynitrobenezene with sodium t-butoxide under specific conditions, namely for 20 min at 110C in 10% dimethoxyethane in toluene, afforded the desired product in 87% yield with exclusive ortho-selectivity. A variety of reaction conditions were screened to obtain the maximum yield. The aromatic nucleophilic substitution of 2,4-dimethoxynitrobenzene with t-butoxide should be carried out under controlled conditions in order to avoid the formation of byproducts, unlike that of dihalogenated activated ben-zenes. Among the formed byproducts, a major compound was elucidated as 2,4-dimethoxy-N-(5-methoxy-2-nitrophenyl)aniline by X-ray crystallography.
- Song, Jiho,Kang, Hae Ju,Lee, Jung Wuk,Wenas, Michelle A.,Jeong, Seung Hwarn,Lee, Taeho,Oh, Kyungsoo,Min, Kyung Hoon
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- TOLL-LIKE RECEPTOR AGONISTS
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Compounds described herein can be used for therapeutic purposes. The compounds can be TLR agonists, such as TLR7 or TLR8 agonists. The compounds can be included in pharmaceutical compositions and used for therapies were being a TLR agonist is useful. The pharmaceutical compositions can include any ingredients, such as carries, diluents, excipients, fillers or the like that are common in pharmaceutical compositions. The compounds can be those illustrated or described herein as well as derivatives thereof, prodrugs thereof, salts thereof, or stereoisomers thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combinations thereof. As such, the compounds can be used as adjuvants in vaccines, as well as for other therapeutic purposes described herein.
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Page/Page column 58; 59
(2015/02/25)
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- Human toll-like receptor 8-selective agonistic activities in 1-alkyl-1 h -benzimidazol-2-amines
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Toll-like receptor (TLR)-8 agonists strongly induce the production of T helper 1-polarizing cytokines and may therefore serve as promising candidate vaccine adjuvants, especially for the very young and the elderly. Earlier structure-based ligand design led to the identification of 3-pentyl-quinoline-2-amine as a novel, human TLR8-specific agonist. Comprehensive structure-activity relationships in ring-contracted 1-alkyl-1H-benzimidazol-2-amines were undertaken, and the best-in-class compound, 4-methyl-1-pentyl-1H-benzo[d]imidazol-2-amine, was found to be a pure TLR8 agonist, evoking strong proinflammatory cytokine and Type II interferon responses in human PBMCs, with no attendant CD69 upregulation in natural lymphocytic subsets. The 1-alkyl-1H-benzimidazol-2-amines represent a novel, alternate chemotype with pure TLR8-agonistic activities and will likely prove useful not only in understanding TLR8 signaling but also perhaps as a candidate vaccine adjuvant.
- Beesu, Mallesh,Malladi, Subbalakshmi S.,Fox, Lauren M.,Jones, Cassandra D.,Dixit, Anshuman,David, Sunil A.
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p. 7325 - 7341
(2014/12/11)
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- PROCESSES FOR PREPARING ISOINDOLINE-1,3-DIONE COMPOUNDS
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Provided herein are processes for preparing an isoindoline- 1.3-dione compound, or an enantiomer or a mixture of enantiomers thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or polymorph thereof.
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Paragraph 00197; 00198
(2014/02/16)
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- Monna, a potent and selective blocker for transmembrane protein with unknown function 16/anoctamin-1
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Transmembrane protein with unknown function 16/anoctamin-1 (ANO1) is a protein widely expressed in mammalian tissues, and it has the properties of the classic calcium-activated chloride channel (CaCC). This protein has been implicated in numerous major physiological functions. However, the lack of effective and selective blockers has hindered a detailed study of the physiological functions of this channel. In this study, we have developed a potent and selective blocker for endogenous ANO1 in Xenopus laevis oocytes (xANO1) using a drug screening method we previously established (Oh et al., 2008). We have synthesized a number of anthranilic acid derivatives and have determined the correlation between biological activity and the nature and position of substituents in these derived compounds. A structure-activity relationship revealed novel chemical classes of xANO1 blockers. The derivatives contain a-NO2 group on position 5 of a naphthyl group-substituted anthranilic acid, and they fully blocked xANO1 chloride currents with an IC 5050 of 0.08 μM for xANO1. Selectivity tests revealed that other chloride channels such as bestrophin-1, chloride channel protein 2, and cystic fibrosis transmembrane conductance regulator were not appreciably blocked by 10~30 μM MONNA. The potent and selective blockers for ANO1 identified here should permit pharmacological dissection of ANO1/CaCC function and serve as potential candidates for drug therapy of related diseases such as hypertension, cystic fibrosis, bronchitis, asthma, and hyperalgesia.
- Oh, Soo-Jin,Hwang, Seok Jin,Jung, Jonghoon,Yu, Kuai,Kim, Jeongyeon,Choi, Jung Yoon,Hartzell, H. Criss,Roh, Eun Joo,Justin Lee
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supporting information
p. 726 - 735
(2013/11/06)
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- Synthesis and characterization of novel starburst phase transfer catalyst
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A new phase transfer catalyst, 3,5-bis[(2-methyl-naphthylene-1 -yl)-phenylamino-phenyl]-butyl-(2methoxy-naphthalene-1 -yl)-phenylammonium bromide (BPBPB) has been synthesized, characterized using spectral analysis and its catalytic activity ascertained. Efficiency of BPBPB is studied using etherification of phenol and compared with tetra butyl ammonium bromide (TBAB). O-Alkylation of naphthol, iV-alkylation of indole and halogen substitution reactions are carried out using BPBPB and its efficiency is compared with reported PTCs. BPBPB gives high yield of product, the time for completion of the reaction is short and is required in a very low concentration. Almost 95% of this catalyst is regenerated and reused.
- Mathew, Siji,Divia,Nair, T.D. Radhakrishnan,Haridas, Karickal R.
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experimental part
p. 1389 - 1393
(2011/01/13)
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- Aromatic nitration in liquid Ag0.51K0.42Na 0.07NO3
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(Figure Presented) Aromatic molecules have a strong affinity for silver(I) and dissolve to a limited extent in Ag0.51K0.42Na 0.07NO3, a low-melting eutectic mixture of silver, potassium, and sodium nitrates. Aromatic nitration in this inorganic ionic liquid leads to products which arise from nonelectrophilic substitution pathways.
- Mascal, Mark,Yin, Lunxiang,Edwards, Ross,Jarosh, Michael
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p. 6148 - 6151
(2008/12/22)
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- Nitration of some aromatic compounds by sodium nitrate in the presence of benzyltriphenylphosphonium peroxodisulfate
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A simple, mild, and regioselective method for the nitration of some aromatic compounds using sodium nitrate in the presence of benzyltriphenylphosphonium peroxodisulfate in acetonitrile as solvent is reported. Mild reaction conditions and good to excellent yields of the products are the noteworthy advantages of the method. Copyright Taylor & Francis Group, LLC.
- Tajik, Hassan,Zolfigol, Mohammad Ali,Albadi, Jalal,Eslami, Ramin
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p. 2771 - 2776
(2008/02/12)
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- 2,3(1H,4H)quinoxalinedione
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2,3(1H,4H)-quinoxalinediones of the formula I STR1 where R1 is hydrogen, an aliphatic radical which has up to 12 carbons and can be substituted by one of the following: phenyl, cyclopentyl, cyclohexyl or --CO--R3, --CO--O--R3 or --CO--NH--R3, where R3 is hydrogen, C1 -C4 -alkyl, phenyl, benzyl or 1-phenylethyl, a cycloaliphatic radical with up to 12 carbons or phenyl, where the cyclic groups in R1 can have up to three of the following substituents: C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy, halogen, nitro, cyano, --CO--O--R3 and --CO--NH--R3 ; R2 is 1-pyrrolyl which can have up to two of the following substituents: C1 -C4 -alkyl, phenyl, phenylsulfonyl, nitro, cyano and --CO--O--R3, --CO--NH--R3, --CH2 --O--R3, --O--R3 and --CH=NO--R3 R radicals are identical or different and are the following: C1 -C4 -alkyl, C1 -C4 -alkoxy, trifluoromethyl, trichloromethyl, trifluoromethoxy, trichloromethoxy, fluorine, chlorine, bromine, iodine, nitro, cyano and --CO--O--R3 and --CO--NH--R3 as well as a fused-on benzene ring; n is 0-3, and 2,3(1H,4H)-quinoxalinediones I' STR2 where R1 has the stated meanings, are suitable as drugs in the treatment of neurodegenerative disorders and neurotoxic disturbances of the central nervous system.
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- Quinoxalines and drugs prepared therefrom
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Quinoxaline-2,3-(1H,4H)-diones of the formula I STR1 and their tautomeric and enantiomeric forms and their physiologically tolerated salts, the variables R, R 1 and R 2 have the meanings specified in claim 1, and are useful for therapeutic treatment of neurodegenerative disorders, neurotoxic disturbances or as antiepileptics, antidepressants and anxiolytics; and drugs composed thereof.
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- Oxidative Derivatisation of Aromatic Ethers
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Reaction of cerium(IV) ammonium nitrate with some naphthyl ethers has been studied as a substitute to traditionally used hydrolytic cleavage method for their identification.One-pot, one-step synthesis of 2,2'-dinitro-1,1'-diethoxy-4,4'-bisnaphthalene; 2,2'-diethoxy-8-nitro-4,4'-bisnaphthalene; 1,8-dinitro-2-methoxynaphthalene; 2-methoxy-8-nitronaphthalene; 1-methoxy-4-nitronaphthalene; 1-ethoxy-4-nitronaphthalene; 4-nitro-1-naphthylbenzoate; 2-methoxy-6-nitronaphthalene; 1-nitro-2-naphthylbenzoate are described.
- Chawla, H. Mohindra,Mittal, Ram S.
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p. 539 - 542
(2007/10/02)
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