- Design, synthesis, and biological evaluation of rutacecarpine derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease
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A series of 3-amino-substituted rutacecarpine derivatives were synthesized to identify novel multitarget-directed ligands (MTDLs) for the treatment of Alzheimer's disease (AD). Biological evaluation showed that most of the synthesized compounds inhibited butyrylcholinesterase (BuChE) and exerted antioxidant effects. Among the synthesized compounds, 6n was subjected to further biological evaluation. Lineweaver–Burk plotting and molecular modeling illustrated that 6n bound simultaneously to the peripheral anionic site (PAS) and catalytic sites (CAS) of BuChE. Furthermore, 6n modulated Aβ aggregation; chelated biometals; presented good absorption, distribution, metabolism, excretion, and toxicity properties; and showed remarkable neuroprotective activity. Previous research has shown that the optimized compound 6n has considerable potential for development as an MTDL for the treatment of AD.
- Wu, Mingfei,Ma, Jie,Ji, Lijun,Wang, Min,Han, Jianfei,Li, Zeng
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Read Online
- Compound herbicide based on dichloro quinolinic acid
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The invention discloses a compound herbicide based on quinclorac, which comprises 20 - 30 parts of quinclorac. Dichloromethane 3-8 parts, synergist 10 - 20 parts, wetting agent 1.5 - 4.5 parts, dispersing agent 1-3 parts, defoaming agent 0.5 - 2.5 parts and water 50 - 70 parts. The synergist inhibits the growth of cells by hindering the synthesis of the protein, and the sprouts of monocotyledonous plants are obtained through young buds of plants. The lower endoderm of the dicotyledonous plant is absorbed and conducted upwards, the seeds and roots absorb conduction, the absorption amount is low, the conduction speed is slow, the growth of young buds and roots is inhibited.
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Paragraph 0015; 0031; 0037; 0041; 0047; 0051; 0057
(2021/11/21)
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- Green synthesis of novel phosphonate derivatives using ultrasonic irradiation
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[Figure not available: see fulltext.] A novel and efficient procedure for the generation of quinazolinone phosphonate derivatives employing the reaction of euparin, isatin or its derivatives, primary amines, dialkyl acetylenedicarboxylates, trimethyl phosphite or triphenyl phosphite, and acidic solution of hydrogen peroxide in aqueous media at ambient temperature under ultrasonic irradiation was developed. Without ultrasonic irradiation, the reaction does not proceed and agitation of the reaction mixture is difficult. Some advantages of this procedure are: short time of reaction, high yields of products, easy isolation of products.
- Sharafian, Shirin,Hossaini, Zinatossadat,Rostami-Charati, Faramarz,Khalilzadeh, Mohammad A.
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p. 1283 - 1291
(2020/11/19)
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- Fluorescent biaryl uracils with C5-dihydro- And quinazolinone heterocyclic appendages in PNA
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There has been much effort to exploit fluorescence techniques in the detection of nucleic acids. Canonical nucleic acids are essentially nonfluorescent; however, the modification of the nucleobase has proved to be a fruitful way to engender fluorescence. Much of the chemistry used to prepare modified nucleobases relies on expensive transition metal catalysts. In this work, we describe the synthesis of biaryl quinazolinone-uracil nucleobase analogs prepared by the condensation of anthranilamide derivatives and 5-formyluracil using inexpensive copper salts. A selection of modified nucleobases were prepared, and the effect of methoxy- or nitro- group substitution on the photophysical properties was examined. Both the dihydroquinazolinone and quinazolinone modified uracils have much larger molar absorptivity (~4-8×) than natural uracil and produce modest blue fluorescence. The quinazolinone-modified uracils display higher quantum yields than the corresponding dihydroquinazolinones and also show temperature and viscosity dependent emission consistent with molecular rotor behavior. Peptide nucleic acid (PNA) monomers possessing quinazolinone modified uracils were prepared and incorporated into oligomers. In the sequence context examined, the nitro-substituted, methoxy-substituted and unmodified quinazolinone inserts resulted in a stabilization (?Tm = +4.0/insert; +2.0/insert; +1.0/insert, respectively) relative to control PNA sequence upon hybridization to complementary DNA. All three derivatives responded to hybridization by the “turn-on” of fluorescence intensity by ca. 3-to-4 fold and may find use as probes for complementary DNA sequences.
- Heidari, Ali,Ghorbani-Choghamarani, Arash,Hajjami, Maryam,Hudson, Robert H.E.
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- Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita
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A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0 mg L?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0 mg L?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.
- Chen, Xiulei,Zhou, Zhen,Li, Zhong,Xu, Xiaoyong
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p. 194 - 200
(2019/09/13)
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- 3-aminosulfonamide substituted rutaecarpine derivative as well as preparation method and application thereof
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The invention discloses a 3-aminosulfonamide substituted rutaecarpine derivative as well asa preparation method and application thereof, and belongs to the technical field of pharmaceutical chemistry.The 3-aminosulfonamide substituted rutaecarpine derivative has very high inhibition performance and very high inhibition selectivity to butyrylcholinesterase, and the inhibition ability to butyrylcholinesterase is 20 times higher than the inhibitory activity to acylcholinesterase, suggesting that the compound can be developed into a medicament for treating Alzheimer's disease.
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Paragraph 0011
(2019/06/07)
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- Chiral Phosphoric Acids in Metal–Organic Frameworks with Enhanced Acidity and Tunable Catalytic Selectivity
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Chiral phosphoric acids are incorporated into indium-based metal–organic frameworks (In-MOFs) by sterically preventing them from coordination. This concept leads to the synthesis of three chiral porous 3D In-MOFs with different network topologies constructed from three enantiopure 1,1′-biphenol-phosphoric acid derived tetracarboxylate linkers. More importantly, all the uncoordinated phosphoric acid groups are periodically aligned within the channels and display significantly enhanced acidity compared to the non-immobilized acids. This facilitates the Br?nsted acid catalysis of asymmetric condensation/amine addition and imine reduction. The enantioselectivities can be tuned (up to '99 % ee) by varying the substituents to achieve a nearly linear correlation with the concentrations of steric bulky groups in the MOFs. DFT calculations suggest that the framework provides a chiral confined microenvironment that dictates both selectivity and reactivity of chiral MOFs.
- Chen, Xu,Jiang, Hong,Li, Xu,Hou, Bang,Gong, Wei,Wu, Xiaowei,Han, Xing,Zheng, Fanfan,Liu, Yan,Jiang, Jianwen,Cui, Yong
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supporting information
p. 14748 - 14757
(2019/09/12)
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- Synthesis and nematicidal evaluation of 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker against Meloidogyne incognita
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To explore new skeleton with nematicidal activity, a series of novel 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker were synthesized and varied fragments were also introduced to increase structure diversity of the new skeleton. Their inhibitory activities in vivo were evaluated against Meloidogyne incognita. The newly prepared compounds A6, A8, A21, A28 and A38 exhibited more than 50% inhibition at the concentration of 20 mg/L. Especially compound A6 displayed 71.4% inhibition against Meloidogyne incognita at the concentration of 20 mg/L. The nematicidal activities varied significantly depending on the types and positions of the substituents, which provided guidance for further structure modification.
- Chen, Xiulei,Jia, Haowu,Li, Zhong,Xu, Xiaoyong
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supporting information
p. 1207 - 1213
(2019/03/29)
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- Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: Preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives
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A convenient two-step synthesis of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate derivatives has been developed starting from commercially available 2-aminobenzoic acids. In step 1, the anthranilic acids are smoothly converted to isatoic anhydrides using solid triphosgene in THF. In step 2, the anhydride electrophiles are reacted with the sodium enolate of ethyl acetoacetate, generated from sodium hydroxide, in warm N,N-dimethylacetamide resulting in the formation of substituted quinolines. A degradation–buildup strategy of the ethyl ester at the 3-position allowed for the construction of the α-hydroxyacetic acid residue required for the synthesis of key arylquinolines involved in an HIV integrase project.
- Jentsch, Nicholas G.,Hume, Jared D.,Crull, Emily B.,Beauti, Samer M.,Pham, Amy H.,Pigza, Julie A.,Kessl, Jacques J.,Donahue, Matthew G.
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p. 2529 - 2536
(2018/10/21)
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- Palladium-Catalyzed Cyclization Reaction of o-Iodoanilines, CO2, and CO: Access to Isatoic Anhydrides
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Isatoic anhydrides, a class of valuable synthetic intermediates and RNA structure probing reagents, are usually prepared with highly toxic phosgene or stoichiometric oxidants. Herein we report a highly selective palladium-catalyzed cyclization reaction for the efficient synthesis of isatoic anhydrides from readily available o-iodoanilines, CO2, and CO. The reaction proceeds under mild conditions and is redox-neutral. Both CO2 and CO are indispensable C1 building blocks for this catalytic reaction.
- Zhang, Wen-Zhen,Zhang, Ning,Sun, Yu-Qian,Ding, Yu-Wei,Lu, Xiao-Bing
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p. 8072 - 8076
(2017/12/08)
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- A method for preparing [...] (by machine translation)
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The present invention discloses a afloqualone preparation method, which comprises: adopting an isatin anhydride as a starting raw material, carrying out nitration, reduction and acetylation to synthesize a key intermediate N-(2-amino-5-acetylaminobenzoyl)o-toluidine, and then carrying out aminolysis, cyclization, fluorine exchange and deprotection to obtain the target product afloqualone. The afloqualone preparation method has characteristics of cheap and easily-available raw materials, production cost reduction, elimination of use of highly-toxic and highly-harmful reagent fluoroacetyl chloride in the existing literature method, safety and environmental protection. In addition, tetrabutyl ammonium bromide is adopted as the phase transfer catalyst of the fluorine exchange reaction so as to substantially improve the conversion rate of the fluorine exchange reaction, and the total yield of the target product afloqualone prepared from the starting raw material isatin anhydride can be more than 60.0%.
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Paragraph 0033-0035
(2017/02/28)
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- Synthesis and Nematicidal Activities of 1,2,3-Benzotriazin-4-one Derivatives against Meloidogyne incognita
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A series of novel 1,2,3-benzotriazin-4-one derivatives were synthesized by the reaction of 3-bromoalkyl-1,2,3-benzotriazin-4-ones with potassium salt of 2-cyanoimino-4-oxothiazolidine in the presence of potassium iodide. Nematicidal assays in vivo showed that some of them exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita, up to 100% at the concentration of 10.0 mg L-1, which indicated that 1,2,3-benzotriazin-4-one derivatives might be potential for novel promising nematicides. The nematicidal activity was influenced by the combination of substituent type, substituted position, and linker length in the molecule. The inhibition rate data at the concentrations of 5.0 and 1.0 mg L-1 for the compounds with high inhibitory activities were also provided. When tested in vitro, none of them showed direct inhibition against M. incognita. The investigation of a significant difference between in vivo and in vitro data is in progress.
- Wang, Gaolei,Chen, Xiulei,Deng, Yayun,Li, Zhong,Xu, Xiaoyong
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p. 6883 - 6889
(2015/08/18)
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- Process for Preparing Primary Intermediates for Dyeing Keratin Fibers
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A process has been developed for preparing 2-methoxymethyl-1,4-benzenediamine (IV-a), other compounds of formula (IV), and the salts thereof, all of which may be used as primary intermediates in compositions for dyeing keratin fibers.
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Paragraph 0044
(2014/05/08)
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- A simple heterocyclic fusion reaction and its application for expeditious syntheses of rutaecarpine and its analogs
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In the search for new inhibitors of cholinesterases, a simple heterocyclic fusion reaction of isatoic anhydride 8 and 3,4-dihydroisoquinoline 22 was discovered which involves a spontaneous dehydrogenation upon heating. Applying the reaction, the bioactive natural alkaloid rutaecarpine and several substituted derivatives out of tryptamines and anthranilic acids or isatoic anhydrides, respectively, can be synthesized without tedious chromatographic purification. This provides simple and fast access to larger amounts of compounds with this privileged structure in medicinal chemistry.
- Huang, Guozheng,Roos, Dominika,Stadtmüller, Patricia,Decker, Michael
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supporting information
p. 3607 - 3609
(2014/06/23)
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- Design, synthesis and biological evaluation of E-ring modified evodiamine derivatives as novel antitumor agents
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A series of novel E-ring modified evodiamine derivatives were designed and synthesized as antitumor agents. Their capacity to interfere with the catalytic activity of topoisomerase I and II was evaluated by the relaxation assay. In vitro antitumor activity results revealed that compound 12 showed good antitumor activity with a broad spectrum. Its binding modes with topoisomerase I and II were clarified by molecular docking.
- Fang, Kun,Dong, Guo-Qiang,Gong, Hai,Liu, Na,Li, Zhen-Gang,Zhu, Shi-Ping,Miao, Zhen-Yuan,Yao, Jian-Zhong,Zhang, Wan-Nian,Sheng, Chun-Quan
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p. 978 - 982
(2014/08/18)
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- Palladium-catalyzed carbonylation of o-iodoanilines for synthesis of isatoic anhydrides
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A novel palladium-catalyzed oxidative double carbonylation of o-iodoanilines for the synthesis of isatoic anhydrides has been developed. The reaction employs readily available o-iodoanilines as the starting materials and proceeds under mild conditions. For extension, palladium-catalyzed oxidative carbonylation of anthranilic acids was developed for the synthesis of substituted isatoic anhydrides in high to excellent yields.
- Gao, Sha,Chen, Ming,Zhao, Mi-Na,Du, Wei,Ren, Zhi-Hui,Wang, Yao-Yu,Guan, Zheng-Hui
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p. 4196 - 4200
(2014/05/20)
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- Biotin-conjugated N-methylisatoic anhydride: A chemical tool for nucleic acid separation by selective 2′-hydroxyl acylation of RNA
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An isatoic anhydride derivative conjugated to a biotin and a disulfide linker was specifically designed for the separation of nucleic acids. Starting from a DNA-RNA mixture, a selective 2′-hydroxyl acylation of RNAs followed by capture with streptavidin-coated magnetic beads and cleavage of the disulfide led to elution of RNAs. the Partner Organisations 2014.
- Ursuegui,Chivot,Moutin,Burr,Fossey,Cailly,Laayoun,Fabis,Laurent
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supporting information
p. 5748 - 5751
(2014/05/20)
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- Facile assembly of two 6-membered fused N-heterocyclic rings: A rapid access to novel small molecules via Cu-mediated reaction
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A rapid, versatile and one-pot Cu-mediated domino reaction has been developed for facile assembly of two six membered fused N-heterocyclic rings leading to novel small molecules as potential inhibitors of PDE4. The Royal Society of Chemistry.
- Adepu, Raju,Sunke, Rajnikanth,Meda, Chandana L. T.,Rambabu,Krishna, G. Rama,Reddy, C. Malla,Deora, Girdhar Singh,Parsa, Kishore V. L.,Pal, Manojit
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supporting information
p. 190 - 192
(2013/02/22)
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- A phosgene and peroxide-free one-pot tandem synthesis of isatoic anhydrides involving anthranilic acid, boc anhydride and 2-chloro-N-methyl pyridinium iodide
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A phosgene and peroxide-free approach for the synthesis of isatoic anhydrides has been described. The synthesis involves the carbamate formation with boc anhydride followed by in situ cyclization to afford the isatoic anhydride. The importance of this synthetic strategy is in the ease of operation, scalability and preparation from readily available raw materials.
- Verma, Chhaya,Sharma, Somesh,Pathak, Arunendra
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supporting information
p. 6897 - 6899
(2019/04/10)
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- Is the 2,3-carbon-carbon bond of indole really inert to oxidative cleavage by Oxone?-Synthesis of isatoic anhydrides from indoles
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A recent report has indicated that the oxidizing agent Oxone does not possess the ability to cleave the 2,3-carbon-carbon bond of indole. Work in our laboratory shows that this is not the case. Indole and a variety of aryl ring substituted derivatives readily react to form synthetically important isatoic anhydrides.
- Nelson, Amber C.,Kalinowski, Emily S.,Czerniecki, Nikolas J.,Jacobson, Taylor L.,Grundt, Peter
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supporting information
p. 7455 - 7457
(2013/11/06)
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- Effective synthesis of 1,5-disubstituted 2,1-benzisothiazol-3(1H)-ones
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A convenient and effective synthesis of novel 1,5-disubstituted 2,1-benzisothiazol-3(1H)-one derivatives is described. The approach involves nitration of inexpensive isatoic anhydride followed by its conversion to 5-nitro-2,1-benzisothiazol-3(1H)-ones in excellent yield and alkylation at the 1-position. The 5-amino group was further derivatized.
- Kharul, Rajendra K.,Prajapati, Pinkal N.,Thorave, Amol A.,Shah, Hardik A.,Dhar, Arghya,Joshi, Darshan A.,Jain, Mukul R.,Patel, Pankaj R.,Pancholi
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experimental part
p. 3265 - 3279
(2011/09/16)
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- Substituent activity relationship studies on new azolo benzoxazepinyl oxazolidinones
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In an effort to discover potent antibacterials based on the entropically favored 'bioactive conformation' approach, a series of novel tricyclic molecules mimicking the conformationally constrained structure of Linezolid is reported. Based on the initial tricyclic molecule 1, the benzazepine derivative 2 was designed where the tricyclic structure had more flexibility around C-N bond compared to 1. While, the molecule 2 was less active, the molecule 3 showed promising antibacterial activity presumably after having obtained rigidity due to pyrrole ring. The syntheses, SAR studies, and evaluation of 3 as a lead compound are reported.
- Das, Jagattaran,Sitaram Kumar,Subrahmanyam,Sastry,Prasad Narasimhulu,Laxman Rao,Kannan,Roshaiah,Awasthi, Riti,Patil, Santosh N.,Sarnaik,Rao Mamidi,Selvakumar,Iqbal, Javed
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p. 8032 - 8042
(2007/10/03)
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- PIPERIDINE DERIVATIVES HAVING CCR3 ANTAGONISM
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The invention provides low molecular compounds having activity which inhibits binding of CCR3 ligands to CCR3 on target cells, i.e. CCR3 antagonists. The invention also provides compounds represented by formula (I) below, pharmaceutically acceptable acid adducts thereof, or pharmaceutically acceptable C1-C6 alkyl adducts thereof, as well as pharmaceutical compositions comprising them as effective ingredients, which are useful for treatment or prevention of diseases associated with CCR3, such as asthma and allergic rhinitis.
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- Syntheses of gem-dinitro heterocyclic compounds, their ring-opening reactions and transformations into indoles, indazoles and benzoxazinones
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The synthesis of some novel 3,3,5,7-tetranitrooxindoles and 4,4- dinitropyrazol-5-ones and their behaviour towards various nucleophiles and electrophiles are reported. Reactions with hydroxide ions or secondary amines produced salts of e.g. 2-amino-3,5-dinitrophenyldinitromethane, which subsequently could be further transformed into indazoles, indoles or benzoxazinones depending upon substrate and conditions used. Mechanisms are discussed.
- Bergman, Jan,Bergman, Solveig,Brimert, Thomas
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p. 10447 - 10466
(2007/10/03)
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