- Synthesis, inhibition properties against xanthine oxidase and molecular docking studies of dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives
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This study focused on synthesis various dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives under the conditions of green chemistry without the use of solvent and catalysts. Their inhibition properties were also investigated on xanthine oxidase (XO) activity. All dimethanol and dicarboxylate derivatives exhibited significant inhibition activities with IC50 values ranging from 0.71 to 2.25 μM. Especially, (1-(3-bromobenzyl)-1H-1,2,3-triazole-4,5-diyl)dimethanol (5c) and dimethyl 1-(4-chlorobenzyl)-1H-1,2,3-triazole-4,5-dicarboxylate (6 g) compounds were found to be the most promising derivatives on the XO enzyme inhibition with IC50 values 0.71 and 0.73 μM, respectively. Moreover, the double docking procedure was to evaluate compound modes of inhibition and their interactions with the protein (XO) at atomic level. Surprisingly, the docking results showed a good correlation with IC50 [correlation coefficient (R2 = 0.7455)]. Also, the docking results exhibited that the 5c, 6f and 6 g have lowest docking scores ?4.790, ?4.755, and ?4.730, respectively. These data were in agreement with the IC50 values. These results give promising beginning stages to assist in the improvement of novel and powerful inhibitor against XO.
- Yagiz, Güler,Noma, Samir Abbas Ali,Altundas, Aliye,Al-khafaji, Khattab,Taskin-Tok, Tugba,Ates, Burhan
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- Design, synthesis and biological evaluation of low molecular weight CXCR4 ligands
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The chemokine receptor CXCR4/stromal cell-derived factor-1 (SDF-1: CXCL12) signaling axis represents a crucial drug target due to its relevance to several diseases such as HIV-1 infection, cancer, leukemia, and rheumatoid arthritis. With the aim of enhancing the binding affinity and anti-HIV activity of a potent CXCR4 ligand as a lead, 23 low molecular weight compounds containing dipicolylamine (Dpa) and cyclam cationic moieties with varying spacers and spatial positioning were designed, synthesized and biologically evaluated. All of the synthesized compounds screened at 1.0 μM in the NanoBRET assay system exhibited >70% inhibition of the binding of a competitive probe TAMRA-Ac-TZ14011 (10 nM) to CXCR4 in the presence of zinc (II) ion. Furthermore, selected compounds 3, 8, 9, 19 and 21 with spatial distances between the next carbon to Dpa and the next carbon to cyclam within the range of 6.5–7.5 ? showed potent binding affinity selective for CXCR4 with IC50 values of 1.6, 7.9, 5.7, 3.5 and 4.5 nM, respectively, with corresponding high anti-HIV activity with EC50s of 28, 13, 21, 28 and 61 nM, respectively, in the presence of zinc (II) ion. Some compounds with remarkably more potent CXCR4-binding affinity than that of an initial lead were obtained. These compounds interact with different but overlapping amino acid residues of CXCR4. The present studies have developed new low molecular weight CXCR4 ligands with high CXCR4-binding and anti-HIV activities, which open avenue into the development of more potent CXCR4 ligands.
- Sakyiamah, Maxwell M.,Kobayakawa, Takuya,Fujino, Masayuki,Konno, Makoto,Narumi, Tetsuo,Tanaka, Tomohiro,Nomura, Wataru,Yamamoto, Naoki,Murakami, Tsutomu,Tamamura, Hirokazu
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supporting information
p. 1130 - 1138
(2019/02/16)
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- THERAPEUTIC COMPOUNDS AND METHODS TO TREAT INFECTION
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Disclosed herein are compounds of formula I: or a salt thereof and compositions comprising a compound of formula I or a pharmaceutically acceptable salt thereof. Also disclosed herein are methods for treating or preventing a bacterial infection in an animal comprising administering to the animal a compound of formula I or a pharmaceutically acceptable salt thereof, alone or in combination with a bacterial efflux pump inhibitor.
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Paragraph 0422-0423
(2019/02/13)
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- Halogenation through Deoxygenation of Alcohols and Aldehydes
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An efficient reagent system, Ph3P/XCH2CH2X (X = Cl, Br, or I), was very effective for the deoxygenative halogenation (including fluorination) of alcohols (including tertiary alcohols) and aldehydes. The easily available 1,2-dihaloethanes were used as key reagents and halogen sources. The use of (EtO)3P instead of Ph3P could also realize deoxy-halogenation, allowing for a convenient purification process, as the byproduct (EtO)3Pa?O could be removed by aqueous washing. The mild reaction conditions, wide substrate scope, and wide availability of 1,2-dihaloethanes make this protocol attractive for the synthesis of halogenated compounds.
- Chen, Jia,Lin, Jin-Hong,Xiao, Ji-Chang
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supporting information
p. 3061 - 3064
(2018/05/28)
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- Silver-Catalyzed Decarboxylative Bromination of Aliphatic Carboxylic Acids
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The silver-catalyzed Hunsdiecker bromination of aliphatic carboxylic acids is described. With Ag(Phen)2OTf as the catalyst and dibromoisocyanuric acid as the brominating agent, various aliphatic carboxylic acids underwent decarboxylative bromination to provide the corresponding alkyl bromides under mild conditions. This method not only is efficient and general but also enjoys wide functional group compatibility. An oxidative radical mechanism involving Ag(II) intermediates is proposed.
- Tan, Xinqiang,Song, Tao,Wang, Zhentao,Chen, He,Cui, Lei,Li, Chaozhong
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supporting information
p. 1634 - 1637
(2017/04/11)
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- Generation of α-imino gold carbenes through gold-catalyzed intermolecular reaction of azides with ynamides
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The generation of α-imino gold carbenes via gold-catalyzed intermolecular reaction of azides and ynamides is disclosed. This new methodology allows for highly regioselective access to valuable 2-aminoindoles and 3-amino-β-carbolines in generally good to excellent yields. A mechanistic rationale for this tandem reaction, especially for the observed high regioselectivity, is supported by DFT calculations.
- Shu, Chao,Wang, Yong-Heng,Zhou, Bo,Li, Xin-Ling,Ping, Yi-Fan,Lu, Xin,Ye, Long-Wu
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supporting information
p. 9567 - 9570
(2015/08/18)
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- A scalable procedure for light-induced benzylic brominations in continuous flow
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A continuous-flow protocol for the bromination of benzylic compounds with N-bromosuccinimide (NBS) is presented. The radical reactions were activated with a readily available household compact fluorescent lamp (CFL) using a simple flow reactor design based on transparent fluorinated ethylene polymer (FEP) tubing. All of the reactions were carried out using acetonitrile as the solvent, thus avoiding hazardous chlorinated solvents such as CCl4. For each substrate, only 1.05 equiv of NBS was necessary to fully transform the benzylic starting material into the corresponding bromide. The general character of the procedure was demonstrated by brominating a diverse set of 19 substrates containing different functional groups. Good to excellent isolated yields were obtained in all cases. The novel flow protocol can be readily scaled to multigram quantities by operating the reactor for longer time periods (throughput 30 mmol h-1), which is not easily possible in batch photochemical reactors. The bromination protocol can also be performed with equal efficiency in a larger flow reactor utilizing a more powerful lamp. For the bromination of phenylacetone as a model, a productivity of 180 mmol h -1 for the desired bromide was achieved.
- Cantillo, David,De Frutos, Oscar,Rincon, Juan A.,Mateos, Carlos,Oliver Kappe
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supporting information
p. 223 - 229
(2014/01/17)
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- One-pot transformation of methylarenes into aromatic aldehydes under metal-free conditions
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On the basis of studies of the transformation of benzylic bromides into the corresponding aromatic aldehydes by treatment with N-methylmorpholine N-oxide, various methylarenes were treated either with DBDMH in the presence of AIBN in acetonitrile at reflux (Method A) or with NBS in CCl4 under irradiation with a tungsten lamp at 30 °C (Method B), followed by treatment with N-methylmorpholine N-oxide to provide aromatic aldehydes in good yields. These methods could be adopted in one-pot transformations of methylarenes into aromatic aldehydes under conditions free of less toxic reagents and transition metals. Copyright
- Tabata, Masayuki,Moriyama, Katsuhiko,Togo, Hideo
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p. 3402 - 3410
(2014/06/09)
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- Antitrypanosomal lead discovery: Identification of a ligand-efficient inhibitor of Trypanosoma cruzi CYP51 and parasite growth
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Chagas disease is caused by the intracellular protozoan parasite Trypanosomal cruzi, and current drugs are lacking in terms of desired safety and efficacy profiles. Following on a recently reported high-throughput screening campaign, we have explored initial structure-activity relationships around a class of imidazole-based compounds. This profiling has uncovered compounds 4c (NEU321) and 4j (NEU704), which are potent against in vitro cultures of T. cruzi and are greater than 160-fold selective over host cells. We report in vitro drug metabolism and properties profiling of 4c and show that this chemotype inhibits the T. cruzi CYP51 enzyme, an observation confirmed by X-ray crystallographic analysis. We compare the binding orientation of 4c to that of other, previously reported inhibitors. We show that 4c displays a significantly better ligand efficiency and a shorter synthetic route over previously disclosed CYP51 inhibitors, and should therefore be considered a promising lead compound for further optimization.
- Andriani, Grasiella,Amata, Emanuele,Beatty, Joel,Clements, Zeke,Coffey, Brian J.,Courtemanche, Gilles,Devine, William,Erath, Jessey,Juda, Cristin E.,Wawrzak, Zdzislaw,Wood, Jodianne T.,Lepesheva, Galina I.,Rodriguez, Ana,Pollastri, Michael P.
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p. 2556 - 2567
(2013/05/09)
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- Direct oxidative conversion of methylarenes into aromatic nitriles
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A variety of methylarenes were successfully converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with NBS or DBDMH in the presence of a catalytic amount of AIBN or BPO, followed by the reaction with molecular iodine in aq NH3 in a one-pot procedure. The present reaction is a useful and practical transition-metal-free method for the preparation of aromatic nitriles from methylarenes.
- Tsuchiya, Daisuke,Kawagoe, Yuhsuke,Moriyama, Katsuhiko,Togo, Hideo
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supporting information
p. 4194 - 4197
(2013/09/12)
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- Direct and selective benzylic oxidation of alkylarenes via C-H abstraction using alkali metal bromides
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A direct benzylic oxidation of alkylarenes via C-H bond abstraction was developed using alkali metal bromides and oxidants under mild conditions. This reaction proceeded with excellent selectivity by thermal oxidation or photooxidation to provide a broad range of carbonyl compounds containing electron-deficient aryl carbonyl compounds in high yields.
- Moriyama, Katsuhiko,Takemura, Misato,Togo, Hideo
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supporting information; experimental part
p. 2414 - 2417
(2012/06/18)
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- N-Halosuccinimide/SiCl4 as general, mild and efficient systems for the α-monohalogenation of carbonyl compounds and for benzylic halogenation
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Combinations of N-halosuccinimide and tetrachlorosilane in acetonitrile were found to be efficient systems for the selective α-monohalogenation of carbonyl compounds as well as for benzylic halogenation under mild conditions.
- Salama, Tarek A.,Novák, Zoltán
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experimental part
p. 4026 - 4029
(2011/08/09)
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- Benzylic bromination of toluene derivatives with boron tribromide
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A facile method for the benzylic bromination of toluene derivatives was developed. Various substituted toluenes were brominated with boron tribromide as bromine source in carbon tetrachloride at room temperature, affording their corresponding benzyl bromides in good yields.
- Chen, Hongbiao,Shen, Litao,Lin, Yuanbin
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experimental part
p. 998 - 1003
(2010/05/18)
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- Novel Compounds, Their Preparation and Use
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Novel compounds of the general formula (I), the use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds may be useful in the treatment and/or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR), in particular the PPARδ subtype.
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Page/Page column 11
(2009/01/24)
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- Visible-light-promoted Wohl-Ziegler functionalization of organic molecules with N-bromosuccinimide under solvent-free reaction conditions
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The visible-light-induced transformation of toluenes with N-bromosuccinimide (NBS) under solvent-free reaction conditions (SFRC) was studied. The reaction took place in spite of the very restricted molecular motion; toluenes could be regioselectively converted to benzyl bromides. Selective radical-chain reactions with NBS were carried out in liquid/liquid and in solid/solid systems; furthermore, reactions could be performed in the presence of air. The radical scavenger TEMPO (=2,2,6,6-tetramethylpiperidin-1- yloxy) completely suppressed the side-chain bromination of toluenes with NBS under SFRC. Electron-withdrawing groups decreased the reactivity of the toluenes, and the Hammett reaction constant ρ+ = -1.7 indicated involvement of polar radical intermediates with electrophilic character.
- Jereb, Marjan,Zupan, Marko,Stavber, Stojan
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scheme or table
p. 555 - 566
(2009/09/06)
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- A chemoselective, easy bromination of (hydroxymethyl)phenols
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A simple and chemoselective method for direct bromination of (hydroxymethyl)phenols via reaction with 2,4,6-trichloro[1,3,5]triazine in N,N-dimethylformamide at room temperature is described. The reaction occurs without affecting the phenolic hydroxy group. Georg Thieme Verlag Stuttgart.
- Nieddu, Giammario,De Luca, Lidia,Giacomelli, Giampaolo
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experimental part
p. 3937 - 3940
(2009/05/26)
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- Asymmetric total synthesis of antiochic acid
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(Chemical Equation Presented) The first asymmetric total synthesis of antiochic acid using bioinspired polyene cyclization strategy is described. Both good yield and good asymmetric induction were obtained.
- Zhao, Yu-Jun,Loh, Teck-Peng
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supporting information; experimental part
p. 2143 - 2145
(2009/05/27)
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- Synthesis and structural and photoswitchable properties of novel chiral host molecules: Axis chiral 2,2′-dihydroxy-1,1′-binaphthyl-appended stiff-stilbene
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(Chemical Equation Presented) Novel photoswitchable chiral hosts having an axis chiral 2,2′-dihydroxy-1,1′-binaphthyl (BINOL)-appended stiff-stilbene, trans-(R,R)- and -(S,S)-1, were synthesized by palladium-catalyzed Suzuki-Miyaura coupling and low-valence titanium-catalyzed McMurry coupling as key steps, and they were fully characterized by various NMR spectral techniques. The enantiomers of trans-1 showed almost complete mirror images in the CD spectra, where two split Cotton effects (exciton coupling) were observed in the β-transitions of the naphthyl chromophore at 222 and 235 nm, but no Cotton effect was observed in the stiff-stilbene chromophore at 365 nm. The structures of (R)-10 and trans-(R,R)-1 were confirmed by X-ray structural analysis. The optimized structure of cis-1 by MO calculations has a wide chiral cavity of 7-8 A in diameter, whereas trans-1 cannot form an intramolecular cavity based on the X-ray data. Irradiation of (R,R)-trans-1 with black light (λ = 365 nm) in CH3CN or benzene at 23°C led to the conversion to the corresponding cis-isomer, as was monitored by 1H NMR, UV - vis, and CD spectra. At the photostationary state, the cis-1/ trans-1 ratio was 86/14 in benzene or 75/25 in CH3CN. On the other hand, irradiation of the cis-1/trans-1 (75/25) mixture in CH3CN with an ultra-high-pressure Hg lamp at 23°C (λ = 410 nm) led to the photostationary state, where the cis-1/trans-1 ratio was estimated to be 9/91 on the basis of the 1H NMR spectra. The cis-trans and trans-cis interconversions could be repeated 10 times without decomposition of the C=C double bond. Thus, a new type of photoswitchable molecule has been developed, and trans-1 and cis-1 were quite durable under irradiation conditions. The guest binding properties of the BINOL moieties of trans- and cis-(R,R)-1 with F -, Cl-, and H2PO4- were examined by 1H NMR titration in CDCl3. Similar interaction with F- and Cl- was observed in trans-1 (host/guest = 1/1, Kassoc = (1.0 ± 0.13) × 103 for F - and (4.6 ± 0.72) × 102 M-1 for Cl-) and cis-1 (host/guest = 1/1, Kassoc = (1.0 ± 0.13) × 103 for F- and (5.9 ± 0.69) × 10 M-1 for Cl-), but H2PO4 - interacted differently: the cis-isomer formed the 1/1 complex (Kassoc = (9.38 ± 2.67) × 10 M-1), whereas multistep equilibrium was expected for the trans-isomer.
- Shimasaki, Toshiaki,Kato, Shin-Ichiro,Ideta, Keiko,Goto, Kenta,Shinmyozu, Teruo
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p. 1073 - 1087
(2007/10/03)
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- NOVEL COMPOUNDS, THEIR PREPARATION AND USE
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Novel compounds of the general formula (I), the use of these compounds as phar- maceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds may be useful in the treatment and/or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR), in particular the PPARδ suptype.
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Page/Page column 28
(2010/02/14)
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- Ethyl 2-formamido-2-(4-iodobenzyl)-3-(4-iodophenyl)propionate and ethyl 2-(3-bromobenzyl)-3-(3-bromophenyl)-2-formamidopropionate
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The title compounds, C19H19I2NO3 and C19H19Br2NO3, are derivatives of α-aminoisobutyric acid with halogen substituents at the para and meta positions, respectively. The ethoxycarbonyl and formamide side chains attached to the Cαatom of the molecule adopt extended and folded conformations, respectively. The crystal structures are stabilized by N -H...O, C - H...O, C - Br...O and C - I...O interactions.
- Damodharan, Lakshminarasimhan,Pattabhi, Vasantha,Behera, Manoranjan,Kotha, Sambasivarao
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p. o216-o218
(2007/10/03)
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- Amine derivatives
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The present invention relates to amine derivatives represented by formula (1) or salts thereof. R3represents C1-C3 alkyl, hydroxylated C1-C5 alkyl, C1-C5 acyl; C2-C5 alkenyl, or a halogen atom; and k, l, and m are each an integer of 1 to 4.) Exhibiting excellent antifungal effect, these compounds are highly useful as antifungal agents, antifungal compositions, drugs, etc.
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- A simple and efficient iodination of alcohols on polymer-supported triphenylphosphine
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A simple, mild, and high-yielding procedure for the iodination of allylic, benzylic, and other primary alcohols using a combination of iodine and imidazole on polymer-supported triphenyl phosphine is described.
- Anilkumar, Gopinathan,Nambu, Hisanori,Kita, Yasuyuki
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p. 190 - 191
(2013/09/06)
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- Triazolylated teritiary amine compound or salt thereof
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A triazolylated tertiary amine compound represented by general formula (I) or a salt thereof, having an aromatase inhibitory activity and being useful for preventing and treating breast cancer, mastopathy, endometriosis, prostatomergaly, etc., wherein A represents a single bond, lower alkylene or carbonyl; B represents lower alkyl, aryl, a 5- or 6-membered heterocyclic group, or a bicyclic fused heterocyclic group; D represents aryl, a 5- or 6-membered heterocyclic group, or a bicyclic fused heterocyclic group; and E represents 4H-1,2,4-triazolyl, 1H-1,2,4-triazolyl or 1H-1,2,3-triazolyl.
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- The preparation of heterobiaryl phosphonates via the Stille coupling reaction
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The Stille cross-coupling reaction between various heteroarylstannanes and substituted bromo-benzylphosphonates was used to prepared heterobiaryl phosphonates in moderate to good yields.
- Kennedy, Gordon,Perboni, Alcide D.
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p. 7611 - 7614
(2007/10/03)
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- Generation of allyl- and benzyllithiums from the corresponding halides by the aid of lithium-tellurium exchange reactions
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A variety of allyl- and benzyllithiums were prepared by lithium-tellurium exchange reactions of allylic and benzylic tellurides generated in situ from the corresponding halides.The produced organolithiums were trapped successfully with electrophiles such as aldehydes, ketones, and trimethylchlorosilane.Benzyllithiums having an alkyl, alkoxy,fluoro, chloro, or cyano substituent(s) on their aromatic ring were generated efficiently in THF.Benzylic tellurides bearing a bromo or iodo substituent afforded a mixture of products under similar conditions arising from the competing lithium-halogen exchange and/or the displacement of the halogen atom with organolithiums used, but they were converted selectively to benzyllithiums in ether without affecting halogen substituents on the benzene ring.Several allyllithiums including dilithioisobutene were generated from allylic halides in a similar way via allylic tellurides.Wurtz-type coupling was negligible in any reactions examined. Key words: Tellurium; Lithium; Allyl; Benzyl; Halide
- Kanda, Takahiro,Kato, Shinzi,Sugino, Takushi,Kambe, Nobuaki,Sonoda, Noboru
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