cas 1877-75-4, 4-Methoxyphenoxyacetic acid

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Diradicals Photogeneration from Chloroaryl-Substituted Carboxylic Acids
With the aim of generating new, thermally inaccessible diradicals, potentially able to induce a double-strand DNA cleavage, the photochemistry of a set of chloroaryl-substituted carboxylic acids in polar media was investigated. The photoheterolytic cleavage of the Ar?Cl bond occurred in each case to form the corresponding triplet phenyl cations. Under basic conditions, the photorelease of the chloride anion was accompanied by an intramolecular electron-transfer from the carboxylate group to the aromatic radical cationic site to give a diradical species. This latter intermediate could then undergo CO2 loss in a structure-dependent fashion, according to the stability of the resulting diradical, or abstract a hydrogen atom from the medium. In aqueous environment at physiological pH (pH=7.3), both a phenyl cation and a diradical chemistry was observed. The mechanistic scenario and the role of the various intermediates (aryl cations and diradicals) involved in the process was supported by computational analysis.
Di Terlizzi, Lorenzo,Protti, Stefano,Ravelli, Davide,Fagnoni, Maurizio
(2022/04/09)

Development of novel phenoxyalkylpiperidines as high-affinity Sigma-1 (σ1) receptor ligands with potent anti-amnesic effect
The sigma-1 (σ1) receptor plays a significant role in many normal physiological functions and pathological disease states, and as such represents an attractive therapeutic target for both agonists and antagonists. Here, we describe a novel series of phenoxyalkylpiperidines based on the lead compound 1-[ω-(4-chlorophenoxy)ethyl]-4-methylpiperidine (1a) in which the degree of methylation at the carbon atoms alpha to the piperidine nitrogen was systematically varied. The affinity at σ1 and σ2 receptors and at Δ8-Δ7 sterol isomerase (SI) ranged from subnanomolar to micromolar Ki values. While the highest-affinity was displayed at the σ1, the increase of the degree of methylation in the piperidine ring progressively decreased the affinity. The subnanomolar affinity 1a and 1-[ω-(4-methoxyphenoxy)ethyl]-4-methylpiperidine (1b) displayed potent anti-amnesic effects associated with σ1 receptor agonism, in two memory tests. Automated receptor–small-molecule ligand docking provided a molecular structure-based rationale for the agonistic effects of 1a and 1b. Overall, the class of the phenoxyalkylpiperidines holds potential for the development of high affinity σ1 receptor agonists, and compound 1a, that appears as the best in class (exceeding by far the activity of the reference compound PRE-084) deserves further investigation.
Abatematteo, Francesca S.,Mosier, Philip D.,Niso, Mauro,Brunetti, Leonardo,Berardi, Francesco,Loiodice, Fulvio,Contino, Marialessandra,Delprat, Benjamin,Maurice, Tangui,Laghezza, Antonio,Abate, Carmen
(2021/12/14)

Design, synthesis and biological evaluation of oxime lacking Psammaplin inspired chemical libraries as anti-cancer agents
In this study, we attempted the chemical simplification of Psammaplin (PsA), while retaining its activity in vitro. Inspired by the previous Structure Activity Relationship (SAR) studies on various PsA analogues and relying on the fact that oxime is metabolically unstable, we initially designed and synthesized a diverse library of PsA analogues and evaluated for cytotoxic activity. Among 32 compounds of Psammaplin analogues synthesized, the compound 10b was almost equally active as parent Psammaplin in vitro.
Ali, Kasim,Chaturvedi, Priyank,Datta, Dipak,Kumar M, Srinivas Lavanya,Meena, Sanjeev,Panda, Gautam
(2020/10/02)

Sulfuryl Fluoride Mediated Synthesis of Amides and Amidines from Ketoximes via Beckmann Rearrangement
A metal-free and redox-neutral method for Beckmann rearrangement employing inexpensive and readily available SO2F2 gas is described. The reported transformation proceeds at ambient temperature and is compatible with a wide range of sterically and electronically diverse aromatic, heteroaromatic, aliphatic and lignin-like oximes providing amides in good to excellent yields. The reaction proceeds through the formation of an imidoyl fluoride intermediate that can also be used for the synthesis of amidines.
Gurjar, Jitendra,Fokin, Valery V.
supporting information
p. 10402 - 10405
(2020/07/25)

Design and synthesis of α-phenoxy-N-sulfonylphenyl acetamides as Trypanosoma brucei Leucyl-tRNA synthetase inhibitors
Human African trypanosomiasis (HAT), caused by the parasitic protozoa Trypanosoma brucei, is one of the fatal diseases in tropical areas and current medicines are insufficient. Thus, development of new drugs for HAT is urgently needed. Leucyl-tRNA synthetase (LeuRS), a recently clinically validated antimicrobial target, is an attractive target for development of antitrypanosomal drugs. In this work, we report a series of α-phenoxy-N-sulfonylphenyl acetamides as T. brucei LeuRS inhibitors. The most potent compound 28g showed an IC50 of 0.70 μM which was 250-fold more potent than the starting hit compound 1. The structure-activity relationship was also discussed. These acetamides provided a new scaffold and lead compounds for the further development of clinically useful antitrypanosomal agents.
Xin, Weixiang,Li, Zezhong,Wang, Qing,Du, Jin,Zhu, Mingyan,Zhou, Huchen
(2019/11/26)

Design and Synthesis of Novel 4-Hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one Derivatives for Use as Herbicides and Evaluation of Their Mode of Action
In order to develop a novel herbicide containing the β-triketone motif, a series of 4-hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one derivatives were designed and synthesized. The bioassay results showed that compound II15 had good pre-emergent herbicidal activity even at a dosage of 187.5 g ha-1. Moreover, compound II15 showed a broader spectrum of weed control when compared with a commercial herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), and displayed good crop safety to Triticum aestivum L. and Zea mays Linn. when applied at 375 g ha-1 under pre-emergence conditions, which indicated its great potential as a herbicide. More importantly, studying the molecular mode of action of compound II15 revealed that the novel triketone structure is a proherbicide of its corresponding phenoxyacetic acid auxin herbicide, which has a herbicidal mechanism similar to that of 2,4-D. The present work indicates that the 4-hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one motif may be a potential lead structure for further development of novel auxin-type herbicides.
Lei, Kang,Li, Pan,Yang, Xue-Fang,Wang, Shi-Ben,Wang, Xue-Kun,Hua, Xue-Wen,Sun, Bin,Ji, Lu-Sha,Xu, Xiao-Hua
p. 10489 - 10497
(2019/10/02)

PRMT5 INHIBITORS AND USES THEREOF
Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
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(2019/04/05)

ROLES OF MODULATORS OF INTERSECTIN-CDC42 SIGNALING IN ALZHEIMER'S DISEASE
Methods of treating Alzheimer's disease and other neurodegenerative and/or neurocognitive and/or neurodevelopmental diseases are described. The methods comprise the administration of compounds that modulate an activity of cell division control protein 42 (Cdc42), such as the interaction between Cdc42 and intersectin (ITSN). Exemplary modulator compounds include thioureas, disulfonamides of fused aromatic systems (e.g., benzofuran), and acyl hydrazones, among others. Some of the modulator compounds act as activators of Cdc42, while others act as inhibitors. In some cases, the modulator compound has dual functionality and the ability of the modulator compound to act as an inhibitor or activator depends on whether or not Cdc42 is already activated in a particular disease stage or biological environment by an upstream activating signal of Cdc42.
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Paragraph 0272; 0275; 0278

(2019/04/14)

Novel pyrazolone derivatives and corresponding europium(III) complexes: Synthesis and properties research
A series of pyrazolone derivatives ligands L1?7 were successfully synthesized and validated by 1H NMR and MS, corresponding europium complexes [EuL1?7(NO3)2]NO3·EtOAc were synthesized. Physico-chemistry properties of title complexes were determined by Elemental analysis, Molar conductance, UV absorption spectra, IR spectra and Thermogravimetric analysis. The title complexes exhibit characteristic red fluorescence of Eu3+. The effect of various substituent groups in ligands on the of title Eu3+ complexes is ordered: Cl > -Br > -OCH3 > -F > -CH3 > -H > -NO2, and [EuL6(NO3)2]NO3·EtOAc containing Cl possesses the strongest fluorescence intensity, so does fluorescence quantum yield. The electrochemical properties indicate that energy gap Eg and LUMO energy level are huge affected by substituent groups, and variation trends of LUMO energy level affected by diverse substituent groups are also different. The prepared title europium complexes have potential application prospects in the fields of photoelectric functional materials and life sciences.
Li, Dewei,Xiong, Suhao,Guo, Tiantong,Shu, Dehua,Xiao, Haihua,Li, Guizhi,Guo, Dongcai
p. 28 - 35
(2018/05/24)

Synthesis and luminescence properties of novel 8-hydroxyquinoline derivatives and their Eu(III) complexes
Six novel 8-hydroxyquinoline derivatives were synthesized using 2-methyl-8-hydroxyquinoline and para-substituted phenol as the main starting materials, and were characterized by 1H nuclear magnetic resonance (NMR), mass spectrometry (MS), ultraviolet (UV) light analysis and infra-red (IR) light analysis. Their complexes with Eu(III) were also prepared and characterized by elemental analysis, molar conductivity, UV light analysis, IR light analysis, and thermogravimetric–differential thermal analysis (TG–DTA). The results showed that the ligand coordinated well with Eu(III) ions and had excellent thermal stability. The structure of the target complex was EuY1–6(NO3)3.2H2O. The luminescence properties of the target complexes were investigated, the results indicated that all target complexes had favorable luminescence properties and that the introduction of an electron-donating group could enhance the luminescence intensity of the corresponding complexes, but the addition of an electron-withdrawing group had the opposite effect. Among all the target complexes, the methoxy-substituted complex (–OCH3) had the highest fluorescence intensity and the nitro-substituted complex (–NO2) had the weakest fluorescence intensity. The results showed that 8-hydroxyquinoline derivatives had good energy transfer efficiency for the Eu(III) ion. All the target complexes had a relatively high fluorescence quantum yield. The fluorescence quantum yield of the complex EuY3(NO3)3.2H2O was highest among all target complexes and was up to 0.628. Because of excellent luminescence properties and thermal stabilities of the Eu(III) complexes, they could be used as promising candidate luminescent materials.
Wu, Yongqiang,Guo, Tiantong,Shu, Dehua,Zhang, Wu,Luan, Fangfei,Shi, Ling,Guo, Dongcai
p. 855 - 862
(2018/07/13)

Synthesis and properties of coumarin derivatives and their terbium complexes
A series of coumarin derivatives obtained from salicylaldehyde and phenol were synthesized. Their corresponding terbium complexes were prepared and characterized by elemental analysis, EDTA titrations, molar conductivity, UVvis spectra, IR spectra, and thermal analysis. The luminescent properties and electrochemical properties of the terbium complexes were also investigated. The results showed that all the terbium complexes exhibited characteristic emissions of terbium ions. The introduction of electron-donating groups can improve the luminescent properties, decrease the HOMO and LUMO energy levels of the terbium complex, while electron-withdrawing groups can weaken the luminescent properties, and increase the HOMO and LUMO energy levels of terbium complex.
Meng, Defen,Xu, De,Li, Dong,Dai, Ming,Li, Guizhi,Guo, Dongcai
p. 5269 - 5280
(2016/06/01)

Synthesis and Biological Activity of Ethyl 4-Alkyl-2-(2-(substituted phenoxy)acetamido)thiazole-5-carboxylate
(Chemical Equation Presented) A series of novel ethyl 4-(methyl or trifluoromethyl)-2-(2-(substituted phenoxy)acetamido)thiazole-5-carboxylates 7a, 7b, 7c, 7d, 7e and 8f, 8g, 8h, 8i, 8j, 8k, 8l, 8m, 8n, 8o, 8p, 8q, 8r were synthesized, and their structures were confirmed by IR, 1H-NMR, MS spectra and elemental analysis. The results of preliminary bioassays show that some of the title compounds exhibit moderate to good herbicidal activities. Compared with the fluorine free compounds 7a, 7b, and 7e, the compounds bearing fluorine 8g, 8j, and 8q showed higher herbicidal activities with 70-100% inhibition against Capsella bursa-pastoris, Amaranthus restroflexus, and Eclipta prostrata at the dosage of 150 g/ha, which indicated that the trifluoromethyl on the thiazole ring was beneficial for the herbicidal activity. Furthermore, compounds 8f, 8g, 8h, 8i, 8j, 8k, 8l, 8m, 8n, 8o, 8p, 8q, 8r were tested for fungicidal activity against Pseudoperonospora cubensis at 500 μg/mL. Compounds 8f and 8q showed the best fungicidal activity with more than 80% inhibition.
Mo, Wenyan,Shi, Yanxia,He, Junbo,Li, Baoju,Peng, Hao,He, Hongwu
p. 183 - 187
(2016/02/10)

A methyl benzofuranacetic [...] biological probe and its preparation method and application
The invention discloses a benzofuran quinoline type biological probe and a preparation method thereof, and application of the benzofuran quinoline type biological probe in detecting a G-quadruplex structure and in the mechanism of action of cryptolepine and G-quadruplex, wherein the biological probe is high in fluorescence intensity and excellent in fluorescence property, and can be applied to specially detecting the G-quadruplex structure and researching the mechanism of action of a cryptolepine derivative and the G-quadruplex. The invention relates to the research whether the cryptolepine derivative acts on the telomere G-quadruplex or the C-MYCG-quadruplex in the promoter region, or on other G-quadruplex structures in vivo; the detection method has the advantages of simple, convenient and quick operation, good selectivity and obvious visualization; the shortcomings of unavailable in-vivo detection, high price, high requirement equipment, relatively complex technical operations and the like of other detection methods are overcome.
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Paragraph 0076; 0077

(2017/02/02)

An Efficient One-Pot Synthesis of 2-(Aryloxyacetyl)cyclohexane-1,3-diones as Herbicidal 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors
4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is an important target for new bleaching herbicides discovery. As a continuous work to discover novel crop selective HPPD inhibitor, a series of 2-(aryloxyacetyl)cyclohexane-1,3-diones were rationally designed and synthesized by an efficient one-pot procedure using N,N′-carbonyldiimidazole (CDI), triethylamine, and acetone cyanohydrin in CH2Cl2. A total of 58 triketone compounds were synthesized in good to excellent yields. Some of the triketones displayed potent in vitro Arabidopsis thaliana HPPD (AtHPPD) inhibitory activity. 2-(2-((1-Bromonaphthalen-2-yl)oxy)acetyl)-3-hydroxycyclohex-2-en-1-one, II-13, displayed high, broad-spectrum, and postemergent herbicidal activity at the dosage of 37.5-150 g ai/ha, nearly as potent as mesotrione against some weeds. Furthermore, II-13 showed good crop safety against maize and canola at the rate of 150 g ai/ha, indicating that II-13 might have potential as a herbicide for weed control in maize and canola fields. II-13 is the first HPPD inhibitor showing good crop safety toward canola.
Wang, Da-Wei,Lin, Hong-Yan,He, Bo,Wu, Feng-Xu,Chen, Tao,Chen, Qiong,Yang, Wen-Chao,Yang, Guang-Fu
p. 8986 - 8993
(2016/12/09)

Synthesis and biological evaluation of aryloxyacetamide derivatives as neuroprotective agents
A series of new aryloxyacetamide derivatives 10a-s and 14a-m are designed and synthesized. Their protective activities against the glutamate-induced cell death were investigated in differentiated rat pheochromocytoma cells (PC12 cells). Most compounds exhibited neuroprotective effects, especially for 10m, 10r, 14b and 14c, which showed potential protection of PC12 cells at three doses (0.1, 1.0, 10 μM). MTT assay, Hoechst 33342/PI double staining, and high content screening (HCS) revealed that pretreatment of the cells with 10m, 10r, 14b and 14c has significantly decreased the extent of cell apoptosis in a dose-dependent manner. The results of western blot analysis demonstrated these compounds suppressed apoptosis of glutamate-induced PC12 cells via caspase-3 pathway. These compounds can be lead compounds for further discovery of neuroprotective agents for treating cerebral ischemic stroke. Basic structure-activity relationships are also presented.
Zhong, Yan,Xu, Yi,Zhang, Ai-Xia,Li, Xiao-Feng,Xu, Zhao-Ying,Li, Ping,Wu, Bin
p. 2526 - 2530
(2016/07/07)

Finding new elicitors that induce resistance in rice to the white-backed planthopper Sogatella furcifera
Herein we report a new way to identify chemical elicitors that induce resistance in rice to herbivores. Using this method, by quantifying the induction of chemicals for GUS activity in a specific screening system that we established previously, 5 candidate elicitors were selected from the 29 designed and synthesized phenoxyalkanoic acid derivatives. Bioassays confirmed that these candidate elicitors could induce plant defense and then repel feeding of white-backed planthopper Sogatella furcifera.
He, Xingrui,Yu, Zhaonan,Jiang, Shaojie,Zhang, Peizhi,Shang, Zhicai,Lou, Yonggen,Wu, Jun
supporting information
p. 5601 - 5603
(2015/11/17)

Synthesis, Characterization and Properties of Novel Coumarin Derivatives and Their Europium Complexes
Seven novel coumarin derivatives derived from salicylaldehyde and phenol were synthesized and characterized by 1H NMR and 13C NMR spectra, mass spectra, infrared spectra and elemental analysis. Their corresponding Eu(III) complexes having general formula EuL1-7(NO3)3·2H2O were successfully prepared and characterized by elemental analysis, EDTA titrimetric, molar conductivity, UV-Vis, FT-IR and thermal performance studies. The luminescence properties, fluorescence quantum yields and the electrochemical properties of the title complexes were investigated. The results showed that the title complexes exhibited characteristic emissions of europium ions and possessed relatively good fluorescence quantum yields. The luminescence intensity of the complex with bromine-substituted group is the strongest among all the title complexes. The introduction of electron-withdrawing groups can increase the luminescence properties and fluorescence quantum yields, decrease the HOMO and LUMO energy levels of the title europium complexes, but electron-withdrawing group conversely. And these title complexes may possibly be useful for studying in luminescent materials field.
Yan, Dong,Li, Dong,Cheng, Guang,Yang, Zehui,Shi, Ling,Guo, Dongcai
p. 849 - 859
(2015/08/24)

Synthesis and luminescence properties of pyrazolone derivatives and their terbium complexes
Seven novel pyrazolone derivatives were synthesized and characterized by 1H NMR and 13C NMR spectra, mass spectra, infrared spectra and elemental analysis. Their terbium complexes were prepared and characterized by elemental analysis, EDTA titrimetric analysis, UV/vis spectra, infrared spectra and molar conductivity, as well as thermal analysis. The fluorescence properties and fluorescence quantum yields of the complexes were investigated at room temperature. The results indicated that pyrazolone derivatives had good energy-transfer efficiency for the terbium ion. All the terbium complexes emitted green fluorescence characteristic of terbium ions, possessed strong fluorescence intensity, and showed relatively high fluorescence quantum yields. Cyclic voltammograms of the terbium complexes were studied and the highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) energy levels of these complexes were estimated.
Xiao, Haihua,Jiang, Xi,Li, Dong,Wu, Limin,Zhang, Wu,Guo, Dongcai
p. 677 - 685
(2015/12/04)

Synthesis and fluorescence properties of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazol derivatives and their terbium complexes
Eight novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazol derivatives have been designed and synthesized, and their corresponding Tb3+ complexes were also prepared successfully. The fluorescence properties and fluorescence quantum yields of the target complexes were investigated, the results showed that the ligands were an efficient sensitizer for Tb3+ luminescence, and the target complexes exhibited characteristic fluorescence emissions of Tb3+ ion. The fluorescence intensity of the complex substituted by chlorine was stronger than that of other complexes. The substituents' nature has a great effect upon the electrochemical properties of the target complexes. The results showed that the introduction of the electron-withdrawing groups tended to decrease the oxidation potential and highest occupied molecular orbital energy levels of the target Tb3+ complexes; however, introduction of the electron-donating groups can increase the corresponding complexes' oxidation potential and highest occupied molecular orbital energy levels.
Zhang, Wu,Chai, Yuchao,Li, Kangyun,Chen, Yanwen,Yan, Dong,Guo, Dongcai
p. 1113 - 1122
(2015/02/19)

Catalyst-free photoredox addition-cyclisations: Exploitation of natural synergy between aryl acetic acids and maleimide
Suitably functionalised carboxylic acids undergo a previously unknown photoredox reaction when irradiated with UVA in the presence of maleimide. Maleimide was found to synergistically act as a radical generating photoxidant and as a radical acceptor, negating the need for an extrinsic photoredox catalyst. Modest to excellent yields of the product chromenopyrroledione, thiochromenopyrroledione and pyrroloquinolinedione derivatives were obtained in thirteen preparative photolyses. In situ NMR spectroscopy was used to study each reaction. Reactant decay and product build-up were monitored, enabling reaction profiles to be plotted. A plausible mechanism, whereby photo-excited maleimide acts as an oxidant to generate a radical ion pair, has been postulated and is supported by UV/Vis. spectroscopy and DFT computations. The radical-cation reactive intermediates were also characterised in solution by EPR spectroscopy. UVA photolyses of aryloxy-, arylthio- and arylamino-acetic acids with maleimide yield oxa-, thia- and aza-tricyclo pyrroledione derivatives in the absence of a photoredox catalyst (see scheme). An intriguing mechanism has been proposed and has been supported and supplemented by NMR monitoring experiments, DFT computations and UV/Vis and EPR spectroscopy.
Manley, David W.,Mills, Andrew,O'Rourke, Christopher,Slawin, Alexandra M. Z.,Walton, John C.
supporting information
p. 5492 - 5500
(2014/05/20)

In silico and pharmacological screenings identify novel serine racemase inhibitors
d-Serine is a coagonist of the N-methyl-d-aspartate (NMDA)-type glutamate receptor and its biosynthesis is catalyzed by serine racemase (SR). The overactivation of the NMDA receptor has been implicated in the development of neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors of SR have potential against these pathological states. Here, we have developed novel inhibitors of SR by in silico screening and in vitro enzyme assay. The newly developed inhibitors have lower IC50 value comparing with that of malonate, one of the standard SR inhibitor. The structural features of novel inhibitors suggest the importance of central amide structure having a phenoxy substituent in their structure for the SR inhibitory activity. The present findings suggest the importance and rational development of new drugs for diseases of NMDAR overactivation.
Mori, Hisashi,Wada, Ryogo,Li, Jie,Ishimoto, Tetsuya,Mizuguchi, Mineyuki,Obita, Takayuki,Gouda, Hiroaki,Hirono, Shuichi,Toyooka, Naoki
supporting information
p. 3732 - 3735
(2014/09/03)

Synthesis, characterization and properties of 1,2,4-triazolo[3,4-b][1,3,4] thiadiazole derivatives and their europium complexes
Eight novel 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives and their corresponding Eu(III) complexes were synthesized and characterized. From the spectral studies it has been concluded that the title Eu(III) complexes display six coordination. The investigation of the luminescence properties of the title complexes showed that the ligands favor energy transfers to the emitting energy level of europium ions. The title Eu(III) complexes exhibited characteristic emissions of europium ions, and possessed strong luminescence intensities, good fluorescence quantum yields, and the highest fluorescence quantum yield is up to 0.522. Furthermore, the luminescence intensity of the complex with chlorine-substituted group is the strongest than that of other complexes. The exploration of the electrochemical properties of the title complexes shows that the introduction of electron-donating groups can increase the HOMO energy levels, LUMO energy levels and the oxidation potential of the complexes, however, the result of introduction of electron-withdrawing groups was just opposite.
Yan, Dong,Xiang, Yu,Li, Kangyun,Chen, Yanwen,Yang, Zehui,Guo, Dongcai
p. 487 - 495
(2014/07/21)

Design, synthesis and molecular docking of amide and urea derivatives as Escherichia coli PDHc-E1 inhibitors
By targeting the ThDP binding site of Escherichia coli PDHc-E1, two new 'open-chain' classes of E. coli PDHc-E1 inhibitors, amide and urea derivatives, were designed, synthesized, and evaluated. The amide derivatives of compound 6d, with 4-NO2 in the benzene ring, showed the most potent inhibition of E. coli PDHc-E1. The urea derivatives displayed more potent inhibitory activity than the corresponding amide derivatives with the same substituent. Molecular docking studies confirmed that the urea derivatives have more potency due to the two hydrogen bonds formed by two NH of urea with Glu522. The docking results also indicate it might help us to design more efficient PDHc-E1 inhibitors that could interact with Glu522.
He, Jun-Bo,Ren, Yan-Liang,Sun, Qiu-Shuang,You, Ge-Yun,Zhang, Li,Zou, Peng,Feng, Ling-Ling,Wan, Jian,He, Hong-Wu
p. 3180 - 3186
(2014/06/09)

Synthesis, Structure, and Properties of the 2-[5-(Aryloxyacetyl)-Amino-1,3,4-Thiadiazol-2-Ylthio] Propionate Derivatives
A series of novel 2-[5-(aryloxyacetyl)-amino-1,3,4-thiadiazol-2-ylthio] propionate derivatives were synthesized in high yield, and their structures were characterized by IR, 1H NMR, 13C NMR, and elemental analysis, coupled with one selected single-crystal X-ray structure determination. The herbicidal activities of target compounds were assessed. The preliminary bioassay results showed that some compounds exhibited moderate to strong herbicidal symptoms in preemergence and postemergence tests. At 150 g/ha, S. tritici. show tolerance, while E. crus-galli L., E. Dahuricus, A. retroflexus, and C. glaucum L. were killed or severely injured. The activity of some compounds was comparable to the commercial herbicide 2,4-D. A suitable electron-withdrawing substituent at the 2-and/or 4-position of the phenyl ring was essential for high herbicidal activity. Moreover, the antifungal activities of the compounds have also been studied. The compounds were found to possess broad-spectrum antifungal activity.
Hu, Bing,Zhai, Yue-Yuan,Zhang, Ling,Zhang, You-Ming,Wei, Tai-Bao
p. 1337 - 1345
(2015/10/29)

PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.
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(2014/07/08)

Selective, potent blockade of the IRE1 and ATF6 pathways by 4-phenylbutyric acid analogues
Background and Purpose 4-Phenylbutyric acid (4-PBA) is a chemical chaperone that eliminates the accumulation of unfolded proteins in the endoplasmic reticulum (ER). However, its chaperoning ability is often weak and unable to attenuate the unfolded protein response (UPR) in vitro or in vivo. To develop more potent chemical chaperones, we synthesized six analogues of 4-PBA and evaluated their pharmacological actions on the UPR. Experimental Approach NRK-52E cells were treated with ER stress inducers (tunicamycin or thapsigargin) in the presence of each of the 4-PBA analogues; the suppressive effects of these analogues on the UPR were assessed using selective indicators for individual UPR pathways. Key Results 2-POAA-OMe, 2-POAA-NO2 and 2-NOAA, but not others, suppressed the induction of ER stress markers GRP78 and CHOP. This suppressive effect was more potent than that of 4-PBA. Of the three major UPR branches, the IRE1 and ATF6 pathways were markedly blocked by these compounds, as indicated by suppression of XBP1 splicing, inhibition of UPRE and ERSE activation, and inhibition of JNK phosphorylation. Unexpectedly, however, these agents did not inhibit phosphorylation of PERK and eIF2α triggered by ER stress. These compounds dose-dependently inhibited the early activation of NF-κB in ER stress-exposed cells. 2-POAA-OMe and 2-POAA-NO2 also inhibited ER stress-induced phosphorylation of Akt. Conclusion and Implications The 4-PBA analogues 2-POAA-OMe, 2-POAA-NO2 and 2-NOAA strongly inhibited activation of the IRE1 and ATF6 pathways and downstream pathogenic targets, including NF-κB and Akt, in ER stress-exposed cells. These compounds may be useful for therapeutic intervention in ER stress-related pathological conditions.
Zhang, Hui,Nakajima, Shotaro,Kato, Hironori,Gu, Liubao,Yoshitomi, Tatsuya,Nagai, Kaoru,Shinmori, Hideyuki,Kokubo, Susumu,Kitamura, Masanori
p. 822 - 834
(2013/10/22)

Aryloxyacetic esters structurally related to α-Asarone as potential antifungal agents
A series of aryloxyacetic ester analogues 8-13 was synthesized based on the potential pharmacophores of the antifungal agents α-Asarone (1) and 2-5. Their antifungal activity was tested in vitro for their growth inhibitory activities against pathogenic fungi. The in vitro antifungal evaluation of these alkyl and aryl esters shows that derivatives 10 displayed the highest antifungal and fungicidal activities against Cryptococcus neoformans and C. gattii. These results support the idea that the phenoxyacetic frame is a potent pharmacophore for the design of potential antifungal drugs. Graphical Abstract: [Figure not available: see fulltext.]
Jimenez, Fabiola,Cruz, Maria Del Carmen,Zuniga, Clara,Martinez, Maria A.,Chamorro, German,Diaz, Francisco,Tamariz, Joaquin
experimental part
p. 33 - 57
(2010/10/20)

Aza-Michael addition of acrylonitrile with 2-aryloxymethylbenzimidazole derivatives under microwave irradiation
A simple, rapid, and highly efficient method has been developed for the aza-Michael addition of acrylonitrile to 2-aryl-oxymethylbenzimidazole derivatives in the presence of anhydrous potassium carbonate under microwave irradiation. A series novel of 1-cyanoethyl-2-aryloxymethylbenzimidazole derivatives have been prepared and characterised by 1H NMR, 13C NMR, IR spectra and elemental analysis.
Wei, Tai-Bao,Hua, Mao-Tang,Shi, Hai-Xiong,Liu, Yong,Zhang, You-Ming
scheme or table
p. 452 - 454
(2010/12/24)

Design, synthesis and in vitro antibacterial/antifungal evaluation of novel 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7(1-piperazinyl)quinoline-3-carboxylic acid derivatives
A series of 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7(1-piperazinyl)quinoline-3-carboxylic acid (norfloxacin) derivatives were prepared according to the principle of combinating bioactive substructures and tested for their activities against five plant pathogenic bacteria and three fungi in vitro. The preliminary bioassays indicated that almost all synthesized target compounds retained the antibacterial activities of norfloxacin and had some antifungal activities as carboxylic acid amide compounds. The activities of compounds 1 and 22 against Xanthomonas oryzae were better than norfloxacin and all tested compounds had better antibacterial activities as compared to the agricultural streptomycin sulfate (a commercial bactericide) against X. oryzae, Xanthomonas axonopodis and Erwinia aroideae. Additionally, compounds 2 and 20 displayed good antifungal activities against Rhizoctonia solani and their inhibition of growth reached 83% and 94% respectively at the concentration of 200 mg/L.
Yu, Zhiyi,Shi, Guanying,Sun, Qiu,Jin, Hong,Teng, Yun,Tao, Ke,Zhou, Guoping,Liu, Wei,Wen, Fang,Hou, Taiping
scheme or table
p. 4726 - 4733
(2010/01/06)

Synthesis and anti-inflammatory activity of 2-aryloxy methyl oxazolines
A series of potential biologically active 2-aryloxy methyl oxazolines 3a-n have been synthesized from substituted hydroxybenzenes 1a-n with good chemical yield. The compounds 3a-n were screened for their anti-inflammatory, ulcerogenic, cyclooxygenase activities and also for their acute toxicity. The potency of the compounds was compared with that of the standard drugs, aspirin and phenyl butazone. The outcome indicates that compounds 3b (48.2%), 3h (48.5%) and 3l (46.5%) offered significant anti-inflammatory activity with low ulcerogenic activity than the standard drugs.
Khanum, Shaukath Ara,Khanum, Noor Fatima,Shashikanth
body text
p. 4597 - 4601
(2009/04/06)

THIADIAZOLE DERIVATIVES, INHIBITORS OF STEAROYL-COA DESATURASE
The present invention relates to substituted thiadiazole compounds of the formula (I) and pharmaceutically acceptable salts thereof, to pharmaceutical compositions containing them and their use in medicine. In particular, the invention relates to compounds for modulating SCD activity.
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Page/Page column 46

(2008/12/07)

Antimalarial activity enhancement in hydroxymethylcarbonyl (HMC) isostere-based dipeptidomimetics targeting malarial aspartic protease plasmepsin
Plasmepsin (Plm) is a potential target for new antimalarial drugs, but most reported Plm inhibitors have relatively low antimalarial activities. We synthesized a series of dipeptide-type HIV protease inhibitors, which contain an allophenylnorstatine-dimethylthioproline scaffold to exhibit potent inhibitory activities against Plm II. Their activities against Plasmodium falciparum in the infected erythrocyte assay were largely different from those against the target enzyme. To improve the antimalarial activity of peptidomimetic Plm inhibitors, we attached substituents on a structure of the highly potent Plm inhibitor KNI-10006. Among the derivatives, we identified alkylamino compounds such as 44 (KNI-10283) and 47 (KNI-10538) with more than 15-fold enhanced antimalarial activity, to the sub-micromolar level, maintaining their potent Plm II inhibitory activity and low cytotoxicity. These results suggest that auxiliary substituents on a specific basic group contribute to deliver the inhibitors to the target Plm.
Hidaka, Koushi,Kimura, Tooru,Ruben, Adam J.,Uemura, Tsuyoshi,Kamiya, Mami,Kiso, Aiko,Okamoto, Tetsuya,Tsuchiya, Yumi,Hayashi, Yoshio,Freire, Ernesto,Kiso, Yoshiaki
scheme or table
p. 10049 - 10060
(2009/04/07)

Polymeric salen-Ti(IV) or V(V) complex catalyzed asymmetric synthesis of O-acetylcyanohydrins from KCN, Ac2O and aldehydes
Polymeric salen-Ti(IV) and V(V) complexes were employed in the enantioselective O-acetyl cyanation of aldehydes with potassium cyanide and acetic anhydride. The crosslinked polymeric salen-Ti(IV) catalyst exhibited good activities and enantioselectivities, up to 91% ee with 99% conversion was obtained at -20°C with 1 mol% of catalyst (based on bimetallic catalytic unit). Moreover, six consecutive recyclings with the easily recovered crosslinked polymeric catalyst showed no obvious decrease in either activity or enantioselectivity. Linear polymeric salen-V(V) catalyst showed good catalytic efficiency too, up to 94% ee with 99% conversion was obtained at -42°C with 5 mol% of catalyst. Graphical Abstract.
Huang, Wei,Song, Yuming,Wang, Jing,Cao, Guoying,Zheng, Zhuo
p. 10469 - 10477
(2007/10/03)

NOVEL SPIRO KETONE AND CARBOXYLIC ACID DERIVATIVES AS SPECIFIC INHIBITORS FOR (PO3H2) SER/(PO3H2)THR-PRO-SPECIFIC PEPTIDYL-PROLYL-CIS/TRANS-ISOMERASES
The invention provides new spiro and carboxylic acid derivatives, pharmaceutically compositions comprising them and their use for the preparation of pharmaceutical compositions.
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Page/Page column 17

(2010/02/07)

Electrochemically-induced spirolactonization of α-(methoxyphenoxy)alkanoic acids into quinone ketals
Anodic oxidation of two series of α-(2)- and α-(4-methoxyphenoxy)alkanoic acids were studied both at the analytical and preparative scales in order to delineate mechanistic aspects of electrochemically induced spirolactonization and to develop synthetically useful orthoquinone bis- and monoketals. Although α-monomethylated carboxylic acids and acetic acid derivatives do not undergo any spiroannulation, α-dimethylated carboxylic acids furnished spirolactones in high yields. A gem-dimethyl effect is invoked to explain these differences in cyclization capacity. Electrooxidation conditions can be selected to furnish either quinone spirolactone bis- or monoketals. Chemoselective monohydrolysis of bisketals can also be accomplished in a stepwise fashion to furnish the corresponding spirolactone monoketals, but the ortho compound unfortunately dimerized in situ via a Diels-Alder process. An ECEC pathway is proposed to rationalize the observed spirolactonizations on the basis of cyclic voltammetry analyses.
Deffieux, Denis,Fabre, Isabelle,Courseille, Christian,Quideau, Stephane
p. 4458 - 4465
(2007/10/03)

Oxidation of non-phenolic β-O-aryl-lignin model dimers catalysed by lignin peroxidase. Comparison with the oxidation induced by potassium 12-tungstocobalt(III)ate
The H2O2-promoted oxidations of the non-phenolic β-O-aryl-lignin model dimers 1-(3,4-dimethoxyphenyl)-2-phenoxyethanol (1) and 2-(4-methoxyphenoxy)-1-phenylethanol (2) catalysed by LiP at pH = 4.0 have been studied. The oxidation of 1 mainly leads to the corresponding ketone, indicating that the prevailing reaction of the intermediate radical cation 1 +. is Cα-H deprotonation. The oxidation of 2 forms 2-(4-methoxyphenoxy)2-phenylethanol (7, an isomer of 2), 2-phenyl-1,4-dioxaspiro[4.5]deca-6,9-dien-8-one (8) and products coming from the cleavage of the C-C bond γ to the more electron rich ring. The formation of all these products can be rationalised by assuming that the main reaction of the intermediate 2+. is a nucleophilic attack of the alcoholic OH group on the ring bearing the positive charge. This leads to a spirocyclohexadienyl radical, which either is then oxidised to the dioxaspirodecadienone 8 or undergoes ring opening to give an alkoxyl radical from which the isomer of 2 and the C-C bond cleavage products may form. Support for this mechanism has been provided by a study of the oxidation of 4-MeOC6H4OCH2CD2OH and by comparing the results with those obtained when the alkoxyl radical 4-MeOC6H4OCH2CD2O. was generated from 4-MeOC6H4OCH2CD2OOtBu. The oxidation of 1 induced by the genuine one-electron oxidant potassium 12-tungstocobalt(III)ate at pH = 4.0 confirms the results obtained with LiP. However, under the same conditions, no fragmentation products were observed in the oxidation of 2, probably due to a fast oxidation, by potassium 12-tungstocobalt(III)ate, of the spirocyclohexadienyl radical.
Baciocchi, Enrico,Bietti, Massimo,Gerini, Maria Francesca,Lanzalunga, Osvaldo,Mancinelli, Simona
p. 1506 - 1511
(2007/10/03)

Kinetics and mechanism of thermal gas-phase elimination of 2-aryloxyacetic acid
Rates of thermal gas-phase elimination of eleven 2-aryloxyacetic acid have been measured over a 45°C temperature range for each compound. Hammett correlation of the present kinetic data with the literature σ0 values of the given substituents gave a reaction ρ constant of 0.69 at 600 K; this is more than that for the gas-phase elimination parameter of 2-aryloxypropanoic acid (ρ = 0.26) and consistent with a transition state with some charge separation, suggesting a partial formation of carbocation. The implications of this observation for the thermal gas-phase elimination of α-aryloxycarboxylic acids are considered.
Al-Awadi, Nouria A.,Kumar, Ajith,Chuchani, Gabriel,Herize, Armando
p. 612 - 616
(2007/10/03)

Poly(phenylenevinylene) analogs with ring substituted polar side chains and their use in the formation of hydrogen bonding based self-assembled multilayers
Poly(arylenevinylene) homopolymers and copolymers with polar hydroxy and carboxy moieties attached to the aromatic phenyl ring were prepared. The copolymers and the related homopolymers are copoly[5-(2-hydroxyethoxy)-2-methoxy-1,4-phenylenevinylene/1,4- phenylenevinylene], co(PHydroxyV-PV), and copoly(5-carboxymethoxy-2-methoxy-1,4-phenylenevinylene/1,4-phenylenevinylene), co(PCarboxyV-PV). For co(PHydroxyV-PV) the photoluminescence and electroluminescence spectra can be adjusted over a range of 100 nm as a function of the percentage of the hydroxy substituted phenyl ring. For co(PCarboxyV-PV) the observed spectral features are a function of the pH from which the final conjugated polymer was prepared. The optical density and photoluminescence of co(PCarboxyV-PV) films prepared from solutions at pH = 12 were significantly blue-shifted compared to polymers prepared from pH = 2 solutions at up to 30% substitution at the phenyl ring. The presence of the polar side chain was used to form self-assembled multilayer films, poly(ethyleneimine)/poly(styrenesulfonate)/co(PHydroxyV-PV), based on hydrogen bonding interactions rather than electrostatic forces. The luminescence spectra in the layered systems were blue-shifted compared to the spin coated films.
Benjamin, Iris,Hong, Haiping,Avny, Yair,Davidov, Dan,Neumann, Ronny
p. 919 - 924
(2007/10/03)

Environmentally desirable synthesis without use of organic solvent. Synthesis of aryloxyacetic acids
A process using only water as solvent is described for the synthesis of aryloxyacetic acids under microwave irradiation.
Villemin, Didier,Hammadi, Mohamed
p. 4337 - 4341
(2007/10/03)

Juvenile hormone like substances: Part XI - Synthesis and biological activities of some juvenile hormone a alogues containing hydroxamate feature
A large number of juvenile hormone analogues (3 to 9) containing hydroxamate function have been synthesized. Preliminary biological screening investigations on one representative, (2,5-dioxo-3-aza-4-oxa-7-methyloctanyl)oxybenzene (3a) reveal a positive juvenile hormonal activity and chemosterilizing effect against potato tuber moth Phthorimaea opercuiella.
Mahajan,Pai, Yogender,Anand, Shalu
p. 333 - 338
(2007/10/03)

Bi(III)-mandelate/DMSO : A New Oxidizing System for the Catalyzed C-C Cleavage of Epoxides
Bi(III)-mandelate was found to be an effective catalyst for the oxidative C-C bond cleavage of epoxides and their transformation into carboxylic acids in anhydrous DMSO medium.
Zevaco, Thomas,Dunach, Elisabet,Postel, Michele
p. 2601 - 2604
(2007/10/02)

Synthesis and plant growth retardant activity of trialkylammonium iodides containing an aromatic ether moiety
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Sharma,Rani,Talwar,Kalsi
p. 135 - 137
(2007/10/02)

Synthesis and Nematicidal Activity of Phenoxypropionic Acid Derivatives
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Hayashi, Masatoshi,Wada, Kojiro,Munakata, Katsura
p. 2653 - 2656
(2007/10/02)

Applicability of Hammett Equation to Insulated Systems - Kinetics of Alkaline Hydrolysis of meta- and para-Substituted Methyl Phenoxyacatates
The kinetics of alkaline hydrolysis of some meta- and para-substituted methyl phenoxyacetates have been determined in 85percent (wt/wt) methanol-water at 10 deg C, 15 deg C, and 20 deg C.The activation parameters have been evaluated from Arrhenius plots and the isokinetic temperature has been analysed.The applicability of Hammett equation to the above reaction has been discussed.The interesting behaviour of halogeno substituents is also discussed.
Gurumurthy, R.,Balakrishnan, N.
p. 154 - 156
(2007/10/02)