- Oxalohydrazide Ligands for Copper-Catalyzed C?O Coupling Reactions with High Turnover Numbers
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Here, we report a class of ligands based on oxalohydrazide cores and N-amino pyrrole and N-amino indole units that generates long-lived copper catalysts for couplings that form the C?O bonds in biaryl ethers. These Cu-catalyzed coupling of phenols with aryl bromides occurred with turnovers up to 8000, a value which is nearly two orders of magnitude higher than those of prior couplings to form biaryl ethers and nearly an order of magnitude higher than those of any prior copper-catalyzed coupling of aryl bromides and chlorides. This ligand also led to copper systems that catalyze the coupling of aryl chlorides with phenols and the coupling of aryl bromides and iodides with primary benzylic and aliphatic alcohols. A wide variety of functional groups including nitriles, halides, ethers, ketones, amines, esters, amides, vinylarenes, alcohols and boronic acid esters were tolerated, and reactions occurred with aryl bromides in pharmaceutically related structures.
- Ray, Ritwika,Hartwig, John F.
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supporting information
p. 8203 - 8211
(2021/03/08)
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- Nickel-Catalyzed Etherification of Phenols and Aryl Halides through Visible-Light-Induced Energy Transfer
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Notwithstanding some progress in nickel-catalyzed etherification of alkanols and arylhalides, the ability of such a Ni-catalyzed transformation employing phenols to diaryl ethers is unsuccessful due to phenolates with much lower reduction potentials, which suppress the oxidation of nickel(II) intermediates into requisite Ni(III) species. We herein report visible-light-initiated, nickel-catalyzed O-arylation of phenols with arylhalides using t-BuNH(i-Pr) as the base and thioxanthen-9-one as the photosensitizer under visible light. This photocoupling exhibits a broad substrate scope.
- Zhu, Da-Liang,Jiang, Shan,Wu, Qi,Wang, Hao,Li, Hai-Yan,Li, Hong-Xi
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supporting information
p. 8327 - 8332
(2021/10/25)
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- Oxalic amide ligands, and uses thereof in copper-catalyzed coupling reaction of aryl halides
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The present invention provides oxalic amide ligands and uses thereof in copper-catalyzed coupling reaction of aryl halides. Specifically, the present invention provides a use of a compound represented by formula I, wherein definitions of each group are described in the specification. The compound represented by formula I can be used as a ligand in copper-catalyzed coupling reaction of aryl halides for the formation of C—N, C—O and C—S bonds.
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Page/Page column 98
(2020/01/09)
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- Toward a treatment of diabesity: In vitro and in vivo evaluation of uncharged bromophenol derivatives as a new series of PTP1B inhibitors
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Protein tyrosine phosphatase 1B (PTP1B) has been considered as a validated biological target for type 2 diabetes treatment, but past endeavors to develop inhibitors of PTP1B into drugs have been unsuccessful. Two challenging aspects are selective inhibition and cell permeability. A structure-based strategy was employed to develop uncharged bromophenols as a new series of PTP1B inhibitors. The most potent compound 22 (LXQ46) inhibited PTP1B with an IC50 value of 0.190 μM, and showed remarkable selectivity over other protein tyrosine phosphatases (PTPs, 20–200 folds). In the SPR study, increasing concentrations of compound 22 led to concentration-dependent increases in binding responses, indicating that compound 22 could bind to the surface of PTP1B via noncovalent means. By treating insulin-resistant C2C12 myotubes with compound 22, enhanced insulin and leptin signaling pathways were observed. Long-term oral administration of compound 22 reduced the blood glucose level of diabetic BKS db mice. The glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) in BKS db mice showed that oral administration of compound 22 could increase insulin sensitivity. In addition, long-term oral administration of compound 22 could protect mice from obesity, which was not the result of toxicity. Our pharmacokinetics results from the rat-based assays showed that orally administered compound 22 was absorbed rapidly from the gastrointestinal tract, extensively distributed to the tissues, and rapidly eliminated from the body. All these results indicate that compound 22 could serve as a qualified agent to treat type II diabetes.
- Li, Xiangqian,Xu, Qi,Li, Chao,Luo, Jiao,Li, Xiuxue,Wang, Lijun,Jiang, Bo,Shi, Dayong
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supporting information
p. 178 - 185
(2019/02/05)
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- Exploring Tandem Ruthenium-Catalyzed Hydrogen Transfer and SNAr Chemistry
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A hydrogen-transfer strategy for the catalytic functionalization of benzylic alcohols via electronic arene activation, accessing a diverse range of bespoke diaryl ethers and aryl amines in excellent isolated yields (38 examples, 70% average yield), is reported. Taking advantage of the hydrogen-transfer approach, the oxidation level of the functionalized products can be selected by judicious choice of simple and inexpensive additives.
- Polidano, Kurt,Reed-Berendt, Benjamin G.,Basset, Ana?s,Watson, Andrew J. A.,Williams, Jonathan M. J.,Morrill, Louis C.
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p. 6716 - 6719
(2017/12/26)
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- A green approach for arylation of phenols using iron catalysis in water under aerobic conditions
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The first efficient iron-catalyzed coupling of aryl iodides with phenols was developed exclusively with water as solvent. The reaction is performed with low cost and readily available FeCl3·6H2O and DMEDA catalytic system providing diaryl ethers in good to excellent yields. The effectiveness of this reaction was further revealed by compatibility with a wide range of functional groups. Moreover, the procedure is rendered simple as this transformation is carried out in the presence of air. Thus, the protocol represents a facile, economical and eco-friendly procedure to access diaryl ethers.
- Sindhu, Kallikkakam S.,Ujwaldev, Sankuviruthiyil M.,Keerthi Krishnan,Anilkumar, Gopinathan
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p. 146 - 150
(2017/03/17)
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- Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B
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Protein tyrosine phosphatases 1B (PTP1B) is a promising and validated therapeutic target to effectively treat T2DM and obesity. However, the development of charged PTP1B inhibitors was restricted due to their low cell permeability and poor bioavailability. Based on active natural products, two series of uncharged catechol derivatives were identified as PTP1B inhibitors by targeting a secondary aryl phosphate-binding site as well as the catalytic site. The most potent inhibitor 22 showed an IC50 of 0.487?μM against PTP1B and strong selectivity (27-fold) over TCPTP. Kinetic studies were also performed that 22 act as a competitive PTP1B inhibitor. The treatment of C2C12 myotubes with 22 markedly increased the phosphorylation levels of IRβ, Akt and IRS1 phosphorylation. The similarity of its action profiling with that produced by insulin suggested its potential as a new non-insulin-dependent drug candidate.
- Li, Xiang-Qian,Xu, Qi,Luo, Jiao,Wang, Li-Jun,Jiang, Bo,Zhang, Ren-Shuai,Shi, Da-Yong
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p. 348 - 359
(2017/05/17)
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- Palladium(II) thiosemicarbazone complex: Synthesis, structure and application to carbon-oxygen cross-coupling reaction
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A simple route for the synthesis of square-planar palladium(II) 3-methyl-thiophene-2-aldehyde thiosemicarbazone complex is described. The composition of the complex has been established by elemental analysis and spectral methods. The molecular structure was confirmed by single crystal X-ray diffraction study. Further, the complex was used as a potential catalyst for the carbon-oxygen cross-coupling reaction of activating, non-activating and deactivating aryl iodides or aryl bromides with p-cresol.
- Suganthy, Pandimuni Kalpaga,Prabhu, Rupesh Narayana,Sridevi, Venugopal Shanmugham
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- Copper-catalyzed Ullmann-type synthesis of diaryl ethers assisted by salicylaldimine ligands
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A series of salicylaldimine ligands were designed to promote the copper-catalyzed Ullmann cross-coupling reaction. After a screening process, 2-((2-isopropylphenylimino)methyl)phenol was found to serve as a good supporting ligand for this reaction. Employing this Schiff-base ligand as a new supporting ligand, the copper-catalyzed coupling reactions of aryl bromides and aryl iodides with various phenols successfully proceeded in good yields under mild conditions. Various diaryl ethers were obtained with excellent yields in dioxane in the presence of K3PO4 and a catalytic amount of copper(I) salt.
- Qian, Cun-Wei,Lv, Wen-Lin,Zong, Qian-Shou,Wang, Mao-Yuan,Fang, Dong
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p. 337 - 340
(2014/02/14)
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- Chemoselective and ligand-free synthesis of diaryl ethers in aqueous medium using recyclable alumina-supported nickel nanoparticles
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An economical and eco-compatible ligand-free protocol for the synthesis of diaryl ethers has been developed using easily accessible alumina-supported nickel nanoparticles as a stable recyclable heterogeneous catalyst in aqueous medium along with a surfactant (SDS) and a mild base (K2CO3). Various sensitive functional groups like allyl, alkoxycarbonyl, formyl, oxo, chloro, bromo, amine and nitro were tolerated in the aforesaid method. Excellent chemoselectivity was demonstrated through competition experiments.
- Ghatak, Avishek,Khan, Sagar,Roy, Rimi,Bhar, Sanjay
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supporting information
p. 7082 - 7088
(2015/02/02)
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- Ullmann-type coupling reaction using metal-organic framework MOF-199 as an efficient recyclable solid catalyst
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A highly porous metal-organic framework (MOF-199) was synthesized, and characterized by several methods including XRD, SEM, TEM, TGA, FT-IR, AAS, and nitrogen physisorption measurements. The MOF-199 was used as an efficient recyclable solid catalyst for the Ullmann-type reaction between aryl iodides and phenols to form diaryl ethers. High conversions were achieved for the transformation at the catalyst concentration of 5 mol%, in the presence of MeONa as a base. Due to the rare availability and the high cost, Cs 2CO3 should only be used for the case of deactivated aryl iodides or deactivated phenols. The MOF-199 catalyst could be facilely separated from the reaction mixture by simple filtration, and could be reused several times without a significant degradation in catalytic activity. The Ullmann-type reaction could only proceed in the presence of the solid MOF-199 catalyst, and the contribution from leached active species in the liquid phase, if any, was negligible.
- Phan, Nam T.S.,Nguyen, Tung T.,Nguyen, Chi V.,Nguyen, Thao T.
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- Ligand-free copper-catalyzed O-arylation of nitroarenes with phenols
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The first example of ligand-free copper-catalyzed O-arylation of nitroarenes with phenols was developed, achieving unsymmetrical diaryl ethers in moderate to excellent yields. This arylation proceeded smoothly without promotion of the ligands, and displayed great functional group compatibility. Thus, the method represents a new, facile, and cost-effective approach to access unsymmetrical diaryl ethers.
- Chen, Jiuxi,Wang, Xingyong,Zheng, Xingwang,Ding, Jinchang,Liu, Miaochang,Wu, Huayue
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supporting information
p. 8905 - 8907
(2012/10/29)
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- Methenamine as an efficient ligand for copper-catalyzed coupling of phenols with aryl halides
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Employing methenamine as a new supporting ligand, the copper-catalyzed coupling reactions of aryl bromides or aryl iodides with various phenols successfully proceeded in good yields under mild conditions. A series of diaryl ethers were obtained with excellent yields in the presence of K 3PO4 and copper(I) salt. Copyright
- Qian, Cunwei,Zong, Qianshou,Fang, Dong
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experimental part
p. 199 - 203
(2012/03/11)
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- Bis(μ-iodo)bis[(-)-sparteine]-dicopper: A versatile catalyst for direct O-Arylation and O-Alkylation of phenols and aliphatic alcohols with haloarenes
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The easy to prepare dimeric bis(μ-iodo)bis[(-)-sparteine]- dicopper ([CuI{(-)-spa}]2 complex) is shown to be versatile catalyst for O-arylation and O-alkylation with various aryl halides with phenols and aliphatic alcohols respectively, including less reactive aryl chlorides, such as chlorobenzene under mild conditions.
- Satyanarayana, Ponnam,Maheswaran, Hariharasarma,Kantam, Mannepalli Lakshmi,Bhargava, Suresh
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supporting information; experimental part
p. 788 - 790
(2011/08/22)
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- Open air O-arylation reaction of phenols with aryl halides catalyzed by polymer-anchored copper(II) complexes
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Two copper complexes were synthesized from macroporous chloromethylated polystyrene beads. The first one was prepared by sequential attachment of imidazole and copper acetate with chloromethylated polystyrene-divinyl benzene copolymer, and the second one was prepared from 4-vinylpyridine and copper acetate with chloromethylated polystyrene-divinyl benzene copolymer. These catalysts showed excellent catalytic activity in O-arylation reaction of aryl halides with phenol in dimethylsulfoxide using potassium carbonate at 130 °C under open air conditions to give diaryl ethers in high yields. Less reactive aryl bromides and aryl chlorides have also been shown to react with phenols to give good yields of the diaryl ethers. The effects of various parameters such as solvent, catalyst from different copper salt and base on the reaction system were studied. The reaction is applicable to a wide variety of substituted aryl halides and phenols with different steric and electronic properties. These catalysts were recovered by simple filtration, and the reusability experiments showed that these catalysts can be used five times without much loss in the catalytic activity.
- Islam, Manirul,Mondal, Sanchita,Mondal, Paramita,Roy, Anupam Singha,Hossain, Dildar,Mobarak, Manir
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experimental part
p. 1 - 11
(2012/02/01)
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- Tripodal N-heterocyclic carbene complexes of palladium and copper: Syntheses, characterization, and catalytic activity
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The tris-palladium tripodal N-heterocyclic carbene (NHC) complexes (timtebtBu){Pd(ICy)I2}3 (4a), (timteb tBu){Pd(PPh3)I2}3 (5a), and (timtebdipp){Pd(PPh3)I2}3 (5b) (timtebtBu = 1,3,5-{tris(tert-butylimidazol-2-ylidene)methyl}-2,4,6- triethylbenzene, 3a; ICy = 1,3-dicyclohexylimidazol-2-ylidene; timteb dipp = 1,3,5-{tris({2,6-diisopropylphenyl}imidazol-2-ylidene)methyl}- 2,4,6-triethylbenzene, 3b) were prepared by reaction of Pd(II) precursors with either the free carbenes or imidazolium salts. Treatment of [Cu(NCMe) 4]X (X = PF6, BF4) with 3a or 3b produced the tris-copper(I) bridged complexes [(timtebR) Cu3(μ3-O)]X (R = tBu, X = PF6, 6a; R = dipp, X = BF4, 6b). Complexes 4a, 5a, and 6a were structurally characterized. The palladium complexes were tested as catalysts for Suzuki-Miyaura and Sonogashira coupling reactions and the copper species also employed for the Sonogashira reaction, as well as for the Ullmann-type arylation of imidazoles and phenols.
- Ellul, Charles E.,Reed, Graham,Mahon, Mary F.,Pascu, Sofia I.,Whittlesey, Michael K.
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experimental part
p. 4097 - 4104
(2011/01/03)
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- Trinuclear copper(I) complexes with triscarbene ligands: Catalysis of C-N and C-C coupling reactions
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Novel synthetic routes for the preparation of trinuclear copper(I) complexes with triscarbene ligands are presented, which yield higher purity products than the one previously described. The first crystal structure of one of these complexes is reported an
- Biffis, Andrea,Tubaro, Cristina,Scattolin, Elena,Basato, Marino,Papini, Grazia,Santini, Carlo,Alvarez, Eleuterio,Conejero, Salvador
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experimental part
p. 7223 - 7229
(2010/02/15)
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- Efficient catalysis of Ullmann-type arylation reactions by a novel trinuclear copper(I) complex with a chelating tricarbene ligand
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A novel trinuclear copper(I) complex with a chelating tricarbene ligand is shown to be an efficient catalyst for the arylation of different classes of compounds containing N-H or O-H functions. Different kinds of azole rings (pyrazole, imidazole, 1,2,4-triazole) can be arylated with comparable efficiencies at relatively mild temperatures (100 °C). The catalyst activates aryl iodides, bromides and even chlorides for the reaction. An unusually strong influence of the nature of the aryl substituent on the reaction yield is observed. The synthetic protocol can be extended to other substrate classes, such as phenols and amides, although the catalytic efficiency with amides is significantly reduced.
- Tubaro, Cristina,Biffis, Andrea,Scattolin, Elena,Basato, Marino
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p. 4187 - 4195
(2008/09/20)
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- SUBSTITUTED 4-ARYLOXY AND 4-ARYLSULFANYL-PHENYL-2-AMINOTHIAZOLES AS INHIBITORS OF CELL PROLIFERATION
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The invention discloses compounds which are substituted 4-aryloxy and 4-arylsulfanyl-phenyl-2-aminothiazoles with anti-cancer activity. The invention futher discloses methods of preparing compounds of the invention. The invention also discloses methods of inhibiting cell proliferation and tumor growth in a subject by administering compounds of the invention to the subject.
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Page/Page column 30-33
(2008/06/13)
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- A general and efficient protocol for the synthesis of biaryl ethers from aryl silyl ethers using Cs2CO3
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A general and efficient one-step procedure has been developed for the synthesis of biaryl ethers via direct coupling of electron-deficient arylhalides or aryl triflates to aryl t-butyldimethylsilyl (TBS) ethers using Cs 2CO3. The protocol was also applied to electron-rich arylhalides by addition of a catalytic amount of copper(I) iodide. The reaction is rapid and provides good to excellent yields.
- Cui, Sun-Liang,Jiang, Zhi-Yong,Wang, Yan-Guang
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p. 1829 - 1831
(2007/10/03)
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- Copper promoted synthesis of diaryl ethers
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An efficient protocol using copper based reagents for the coupling of aryl halides with phenols to generate diaryl ethers is described. A copper(I) complex, [Cu(CH3CN)4]ClO4, or the readily available copper(II) source, CuCO3·Cu(OH)2· H2O (in combination with potassium phosphate), can be used. Aryl halides and phenols with different steric and electronic demands have been used to assess the efficiency of the procedure. The latter source of copper gives better yields under all conditions.
- Ghosh, Rajshekhar,Samuelson, Ashoka G.
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p. 1390 - 1393
(2007/10/03)
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- Synthesis and evaluation of substituted 4-aryloxy- and 4-arylsulfanyl- phenyl-2-aminothiazoles as inhibitors of human breast cancer cell proliferation
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Several substituted 4-aryloxy- and 4-arylsulfanyl-phenyl-2-aminothiazoles were synthesized and evaluated for cytotoxic activity against estrogen-positive, estrogen-negative, and adriamycin-resistant human breast cancer cell lines. 4-[4′-(3,4-Dichlorophenoxy)-phenyl]-thiazol-2-yl ammonium iodide demonstrated potent activity against both estrogen-positive and negative breast cancer cell lines with low micromolar (μM) GI50 values. In addition, we have identified several 2-aminothiazoles that demonstrated selective potency for the adriamycin-resistant and estrogen-negative breast cancer cell lines. The results suggest that these 2-aminothiazoles represent lead compounds for evaluation in animal models of breast cancer.
- Gorczynski, Michael J.,Leal, Rachel M.,Mooberry, Susan L.,Bushweller, John H.,Brown, Milton L.
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p. 1029 - 1036
(2007/10/03)
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- Cytotoxic and anticonvulsant aryloxyaryl Mannich bases and related compounds
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A series of 1-(4-aryloxyphenyl)-3-diethylamino-1-propanone hydrochlorides 3a-3e and related compounds 3f, 3g and 4a-4d were synthesised. In addition, a group of 4-(4-aryloxyphenyl)-3-(4-aryloxyphenylcarbonyl)-1-ethyl-4-piperidinol hydrochlorides 6a-6e were prepared which incorporated most of the structural features of 3a-3e. All of these compounds displayed cytotoxic properties towards murine L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. A number of these compounds possessed noteworthy potencies towards seven human colon cancer cell lines. Some correlations were noted between the IC 50 values generated in the different screens and the σ, π and molar refractivity constants of the aryl substituents as well as with the volumes and solvent accessible surface areas of various basic groups. Molecular modelling of representative compounds revealed structural features, which may have contributed to the varying potencies noted. In general, the compounds in series 6 were well tolerated when administered to mice. Anticonvulsant properties were demonstrated by a number of compounds in the maximal electroshock (MES) screen when administered intraperitoneally to mice while 4c and 6e afforded protection in the MES test when given orally to rats.
- Vashishtha, Sarvesh C.,Zello, Gordon A.,Nienaber, Kurt H.,Balzarini, Jan,De Clercq, Erik,Stables, James P.,Dimmock, Jonathan R.
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- (Aryloxy)aryl semicarbazones and related compounds: A novel class of anticonvulsant agents possessing high activity in the maximal electroshock screen
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A number of (aryloxy)aryl semicarbazones and related compounds were synthesized and evaluated far anticonvulsant activities. After intraperitoneal injection to mice, the semicarbazones were examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and neurotoxicity (NT) screens. The results indicated that greater protection was obtained in the MES test than the scPTZ screen. Quantitation of approximately one-third of the compounds revealed an average protection index (PI, i.e. TD50/ED50) of approximately 9. After oral administration to rats, a number of compounds displayed significant potencies in the MES screen (ED50 of 1-5 mg/kg) accompanied by very high protection indices. In fact over half the compounds had PI figures of greater than 100, and two were in excess of 300. The compounds were essentially inactive in the scPTZ and NT screens after oral administration to rats. Various compounds displayed greater potencies and PI figures in the mouse intraperitoneal and rat oral screens than three reference clinically used drugs. The data generated supported a binding site hypothesis. Quantitative structure-activity relationships indicated a number of physicochemical parameters which contributed to activity in the MES screen. X-ray crystallography of five compounds suggested the importance of certain interatomic distances and bond angles for activity in the mouse and rat MES screens.
- Dimmock, Jonathan R.,Puthucode, Ramanan N.,Smith, Jennifer M.,Hetherington, Mark,Quail, J. Wilson,Pugazhenthi, Uma,Lechler, Terry,Stables, James P.
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p. 3984 - 3997
(2007/10/03)
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- SYNTHESIS AND REACTIVITY OF ARYLOXYCUMENYL CHLORIDES
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A series of derivatives of aryloxycumenyl chlorides containing substituents (methyl, methoxy, fluorine, and chlorine) at positions 3 and 4 of the aryl ring were synthesized.From the results from their solvolysis in 90 vol. percent aqueous acetone it was concluded that there is strong transfer of the electronic effects through the diphenyl ether system comparable with that in biphenyl.
- Litvinenko, L. M.,Benndorf, V.,Popova, R. S.,Popov, A. F.,Tormosin, I. I.
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p. 680 - 683
(2007/10/02)
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