- Synthesis of new piperazinyl-pyrrolo[1,2-: A] quinoxaline derivatives as inhibitors of Candida albicans multidrug transporters by a Buchwald-Hartwig cross-coupling reaction
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Two series of piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives were prepared via a Buchwald-Hartwig cross-coupling reaction and then evaluated for their ability to inhibit the drug efflux activity of CaCdr1p and CaMdr1p transporters of Candida albicans overexpressed in a Saccharomyces cerevisiae strain. In the initial screening of twenty-nine piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives, twenty-three compounds behaved as dual inhibitors of CaCdr1p and CaMdr1p. Only four compounds showed exclusive inhibition of CaCdr1p or CaMdr1p. Further biological investigations were developed and for example, their antifungal potential was evaluated by measuring the growth of control yeast cells (AD1-8u-) and efflux pump-overexpressing cells (AD-CDR1 and AD-MDR1) after exposition to variable concentrations of the tested compounds. The MIC80 values of nineteen compounds ranging from 100 to 901 μM for AD-CDR1 demonstrated that relative resistance index (RI) values were between 8 and 274. In comparison, only seven compounds had RI values superior to 4 in cells overexpressing Mdr1p. These results indicated substrate behavior for nineteen compounds for CaCdr1p and seven compounds for CaMdr1p, as these compounds were transported via MDR transporter overexpressing cells and not by the AD1-8u- cells. Finally, in a combination assay with fluconazole, two compounds (1d and 1f) have shown a synergistic effect (fractional inhibitory concentration index (FICI) values ≤ 0.5) at micromolar concentrations in the AD-MDR1 yeast strain overexpressing CaMdr1p-protein, indicating an excellent potency toward chemosensitization.
- Guillon, Jean,Nim, Shweta,Moreau, Stéphane,Ronga, Luisa,Savrimoutou, Solène,Thivet, Elisabeth,Marchivie, Mathieu,Di Pietro, Attilio,Prasad, Rajendra,Le Borgne, Marc
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- Simple and green synthesis of benzimidazoles and pyrrolo[1,2-: A] quinoxalines via Mamedov heterocycle rearrangement
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A method for the synthesis of coupling compounds of benzimidazoles and pyrrolo[1,2-a]quinoxalines via Mamedov Heterocycle Rearrangement is reported here. This method was conducted at room temperature and only solvent (HOAc) was required. A series of 4-(1H-benzo[d]imidazol-2-yl)pyrrolo[1,2-a]quinoxaline derivatives were obtained in moderate to good yields.
- Li, Shichen,Feng, Lei,Ma, Chen
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supporting information
p. 9320 - 9323
(2021/06/14)
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- PEG-400 as a carbon synthon: Highly selective synthesis of quinolines and methylquinolines under metal-free conditions
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A metal-free, peroxide-free, and efficient procedure for the highly selective synthesis of quinolines and methylquinolines was reported. The main feature of this method was that the same substrate can produce quinolines and methylquinolines, respectively, under different reaction conditions. PEG-400 was used as both a reactant and solvent in this reaction. The utility of the designed procedure was also demonstrated by the derivatization of the products to bioactive compounds. This journal is
- Ding, Chengcheng,Feng, Kaili,Li, Shichen,Ma, Chen
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supporting information
p. 5542 - 5548
(2021/08/16)
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- Synthesis of oxazolidinones through ring-opening and annulation of vinylene carbonate with 2-pyrrolyl/indolylanilines under Rh(iii) catalysis
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Herein, we have developed a rhodium-catalyzed C-H functionalization and subsequent intramolecular ring-opening/cyclization of vinylene carbonate with 2-pyrrolyl/indolylanilines, which leads to oxazolidinones in moderate to good yields. In this transformation, vinylene carbonate only eliminates one oxygen atom rather than -CO3 or CO2. Furthermore, some control experiments are conducted to elucidate the reaction mechanism. This journal is
- Hu, Fang-Peng,Zhang, Xue-Guo,Wang, Meng,Wang, He-Song,Huang, Guo-Sheng
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supporting information
p. 11980 - 11983
(2021/12/01)
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- Pyrrolyl group-containing compound, polymer, mixture, composition, and organic electronic device
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The invention discloses a pyrrolyl-containing compound, a high polymer, a mixture, a composition and an organic electronic device. The pyrrolyl-containing compound contains a structure represented bya general formula (1), forms a condensed ring with other functional units through a pyrrolyl group, and is adjusted in the aspects of molecular stability and transmission performance. The pyrrolyl-containing compound disclosed by the invention is used in an OLED, particularly used as a light emitting layer material, and can provide higher device performance.
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Paragraph 0168-0173; 0180-0185
(2020/11/26)
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- Tin(ii) chloride dihydrate/choline chloride deep eutectic solvent: Redox properties in the fast synthesis of: N -arylacetamides and indolo(pyrrolo)[1,2- a] quinoxalines
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In this contribution a physicochemical, IR and Raman characterization for the tin(ii) chloride dihydrate/choline chloride eutectic mixture is reported. The redox properties of this solvent were also studied by cyclic voltammetry finding that it can be successfully used as an electrochemical solvent for electrosynthesis and electroanalytical processes and does not require negative potentials as verified by the reduction of nitrobenzene. The potential use of this eutectic mixture as a redox solvent was further explored in obtaining aromatic amines and N-arylacetamides starting from a wide variety of nitroaromatic compounds. In addition, a fast synthetic strategy for the construction of a series of indolo(pyrrolo)[1,2-a]quinoxalines was developed by reacting 1-(2-nitrophenyl)-1H-indole(pyrrole) with aldehydes. This simple protocol offers a straightforward method for the construction of the target quinoxalines in short reaction times and high yields where the key step involves a tandem one-pot reductive cyclization-oxidation.
- Bejarano, Oscar Rodríguez,Ochoa-Puentes, Cristian,Pe?a-Solórzano, Diana,Trujillo, Sergio Alfonso
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p. 40552 - 40561
(2020/11/18)
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- Pyrrolo[1,2-a]quinoxalines: Insulin Mimetics that Exhibit Potent and Selective Inhibition against Protein Tyrosine Phosphatase 1B
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PTP1B dephosphorylates insulin receptor and substrates to modulate glucose metabolism. This enzyme is a validated therapeutic target for type 2 diabetes, but no current drug candidates have completed clinical trials. Pyrrolo[1,2-a]quinoxalines substituted at positions C1–C4 and/or C7–C8 were found to be nontoxic to cells and good inhibitors in the low- to sub-micromolar range, with the 4-benzyl derivative being the most potent inhibitor (0.24 μm). Some analogues bearing chlorine atoms at C7 and/or C8 kept potency and showed good selectivity compared to TCPTP (selectivity index '40). The most potent inhibitors behaved as insulin mimetics by increasing glucose uptake. The 4-benzyl derivative inhibited insulin receptor substrate 1 and AKT phosphorylation. Molecular docking and molecular dynamics simulations supported a putative binding mode for these compounds to the allosteric α3/α6/α7 pocket, but inconsistent results in enzyme inhibition kinetics were obtained due to the high tendency of these inhibitors to form stable aggregates. Computational calculations supported the druggability of inhibitors.
- García-Marín, Javier,Griera, Mercedes,Sánchez-Alonso, Patricia,Di Geronimo, Bruno,Mendicuti, Francisco,Rodríguez-Puyol, Manuel,Alajarín, Ramón,de Pascual-Teresa, Beatriz,Vaquero, Juan J.,Rodríguez-Puyol, Diego
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supporting information
p. 1788 - 1801
(2020/09/15)
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- Catalyst-Controlled Chemodivergent Annulation to Indolo/Pyrrolo-Fused Diazepine and Quinoxaline
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Catalyst-controlled chemodivergent annulation between o-indolo anilines and diazo compounds has explored for the synthesis of indolo-fused diazepine and quinoxaline. Under the Rh(III) catalyst, reaction proceeded through the free amine assisted C2?H activation followed by amidation leading to the diazepino[1,7-a]indole in a highly selective manner. While with Ru(II) catalyst, reaction involves formation Ru?carbene complex followed by ?NH2 group insertion and cascade cyclization via metallo-ene type reaction, β-hydride elimination to furnish the indolo[1,2-a]quinoxaline as the predominating product. This strategy directs modular approach towards the construction of unique indolo-fused diazepine/quinoxaline as well as pyrrolo-fused diazepine/quinoxaline scaffolds in excellent yields. (Figure presented.).
- Dhole, Sandip,Chiu, Wei-Jung,Sun, Chung-Ming
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supporting information
p. 2916 - 2925
(2019/04/26)
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- Optimization of Drug Candidates That Inhibit the D-Loop Activity of RAD51
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RAD51 is the central protein in homologous recombination (HR) repair, where it first binds ssDNA and then catalyzes strand invasion via a D-loop intermediate. Additionally, RAD51 plays a role in faithful DNA replication by protecting stalled replication forks; this requires RAD51 to bind DNA but may not require the strand invasion activity of RAD51. We previously described a small-molecule inhibitor of RAD51 named RI(dl)-2 (RAD51 inhibitor of D-loop formation #2, hereafter called 2 h), which inhibits D-loop activity while sparing ssDNA binding. However, 2 h is limited in its ability to inhibit HR in vivo, preventing only about 50 % of total HR events in cells. We sought to improve upon this by performing a structure–activity relationship (SAR) campaign for more potent analogues of 2 h. Most compounds were prepared from 1-(2-aminophenyl)pyrroles by forming the quinoxaline moiety either by condensation with aldehydes, then dehydrogenation of the resulting 4,5-dihydro intermediates, or by condensation with N,N′-carbonyldiimidazole, chlorination, and installation of the 4-substituent through Suzuki–Miyaura coupling. Many analogues exhibited enhanced activity against human RAD51, but in several of these compounds the increased inhibition was due to the introduction of dsDNA intercalation activity. We developed a sensitive assay to measure dsDNA intercalation, and identified two analogues of 2 h that promote complete HR inhibition in cells while exerting minimal intercalation activity.
- Budke, Brian,Tueckmantel, Werner,Miles, Kelsey,Kozikowski, Alan P.,Connell, Philip P.
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supporting information
p. 1031 - 1040
(2019/04/30)
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- Unexpected activated carbon-catalyzed pyrrolo[1,2-a]quinoxalines synthesis in water
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An interesting and recyclable activated carbon/water catalytic system for efficient synthesis of pyrrolo[1,2-a]quinoxaline derivatives was developed. The intramolecular C–N and C–C bond can be easily constructed in water under mild condition. This reaction features a broad substrate scope, a good tolerance to water and air, metal-free, additive-free and redox reagent-free.
- Sun, Qi,Liu, Liyan,Yang, Yu,Zha, Zhenggen,Wang, Zhiyong
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supporting information
p. 1379 - 1382
(2019/05/04)
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- A new pathway to pyrrolo[1,2-a]quinoxalines via solvent-free one-pot strategy utilizing FeMoSe nanosheets as efficient recyclable synergistic catalyst
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FeMoSe nanocatalyst was synthesized using solvothermal approach from readily available precursors, namely Mo(CO)6, FeSO4 and Se, and characterized by spectroscopic and microscopic analyses. The FeMoSe material offered high catalytic
- To, Tuong A.,Nguyen, Chuc T.,Tran, My H.P.,Huynh, Thai Q.,Nguyen, Tung T.,Le, Nhan T.H.,Nguyen, Anh D.,Tran, Phong D.,Phan, Nam T.S.
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p. 163 - 173
(2019/08/02)
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- Metal-Free Synthesis of Pyrrolo[1,2- a ]quinoxalines Mediated by TEMPO Oxoammonium Salts
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We herein describe a novel TEMPO oxoammonium salt initiated Pictet-Spengler reaction of imines, generated in situ from carbonyl compounds and pyrrole- or indole-containing substrates, to afford 4,5-dihydropyrrolo[1,2- a ]quinoxalines or 5,6-dihydroindolo[1,2- a ]quina-oxalines in good to excellent yields. Moreover, a one-pot synthesis of a biologically important quinoxaline is achieved via a cyclization-dehydrogenation process using one equivalent of the oxoammonium salt.
- Huo, Heng-Rui,Tang, Xiang-Ying,Gong, Yue-Fa
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p. 2727 - 2740
(2018/06/20)
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- Synthesis and antimalarial activity of new enantiopure aminoalcoholpyrrolo[1,2-a]quinoxalines
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Background: We prepared a novel series of enantiopure mefloquine analogues with pyrrolo[ 1,2-a]quinoxaline core in order to fight Plasmodium falciparum resistant strain. Objectives: To observe the influence of pyrrolo[1,2-a]quinoxaline core versus quinoline core on the antimalarial activity. Method: Four enantiopure aminoalcoholpyrrolo[1,2-a]quinoxalines 2 were synthetized via Sharpless asymmetric dihydroxylation reaction in eight steps. Their antimalarial activity was evaluated on two Plasmodium falciparum strains 3D7 and W2 with a SYBR Green I fluorescence-based method and their cytotoxicity was measured on four cell lines HepG2, THP-1, CHO and HFF. Results: IC50 values of the four compounds 2 were close to the micromolar against the two P. falciparum strains. They were more active against P. falciparum strain W2 vs. P. falciparum strain 3D7. (R)-enantiomers were always more active than their (S)-counterpart whatever the strain. Selectivity indexes of compounds 2 were lower than 100. Conclusion: A novel series of enantiopure aminoalcohols with pyrrolo[1,2-a]quinoxaline core were synthesized in eight steps. They displayed IC50 values close to the micromolar against two P. falciparum strains 3D7 and W2. Although, In this series, 2,8-bistrifluoromethylquinoline was a best core than pyrrolo[1,2-a]quinoxaline for an optimal antimalarial activity, the pyrroloquinoxaline 2b showed an interesting antimalarial activity.
- Jonet, Alexia,Guillon, Jean,Mullié, Catherine,Cohen, Anita,Bentzinger, Guillaume,Schneider, Jérémy,Taudon, Nicolas,Hutter, Sebastien,Azas, Nadine,Moreau, Stephane,Savrimoutou, Solene,Agnamey, Patrice,Dassonville-Klimpt, Alexandra,Sonnet, Pascal
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p. 293 - 303
(2018/05/23)
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- Synthesis, Characterization, and Properties of Bis-BN Ullazines
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A series of bis-BN ullazine derivatives, including the parent species, were synthesized in a small number of steps from commercially available materials. X-ray crystallographic analysis revealed that bis-BN ullazines have rigid and planar frameworks. Most of the bis-BN ullazines are stable toward air and moisture. In addition, the absorption and emission bands of these ullazines are blue-shifted, compared to those of their carbonaceous ullazine analogs.
- Li, Chenglong,Liu, Yuming,Sun, Zhe,Zhang, Jinyun,Liu, Meiyan,Zhang, Chen,Zhang, Qian,Wang, Hongjuan,Liu, Xuguang
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supporting information
p. 2806 - 2810
(2018/05/29)
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- Design, synthesis and antimalarial activity of novel bis{N-[(pyrrolo[1,2-a]quinoxalin-4-yl)benzyl]-3-aminopropyl}amine derivatives
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Novel series of bis- and tris-pyrrolo[1,2-a]quinoxaline derivatives 1 were synthesized and tested for in vitro activity upon the intraerythrocytic stage of W2 and 3D7 Plasmodium falciparum strains. Biological results showed good antimalarial activity with IC50 in the μM range. In attempting to investigate the large broad-spectrum antiprotozoal activities of these new derivatives, their properties toward Leishmania donovani were also investigated and revealed their selective antiplasmodial profile. In parallel, the in vitro cytotoxicity of these molecules was assessed on the human HepG2 cell line. Structure–activity relationships of these new synthetic compounds are discussed here. The bis-pyrrolo[1,2-a]quinoxalines 1n and 1p were identified as the most potent antimalarial candidates with selectivity index (SI) of 40.6 on W2 strain, and 39.25 on 3D7 strain, respectively. As the telomeres of the parasite could constitute an attractive target, we investigated the possibility of targeting Plasmodium telomeres by stabilizing the Plasmodium telomeric G-quadruplexes through a FRET melting assay by our new compounds.
- Guillon, Jean,Cohen, Anita,Gueddouda, Nassima Meriem,Das, Rabindra Nath,Moreau, Stéphane,Ronga, Luisa,Savrimoutou, Solène,Basmaciyan, Louise,Monnier, Alix,Monget, Myriam,Rubio, Sandra,Garnerin, Timothée,Azas, Nadine,Mergny, Jean-Louis,Mullié, Catherine,Sonnet, Pascal
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p. 547 - 563
(2017/11/10)
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- N-Picolinamides as ligands for Ullmann-type C-N coupling reactions
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The use of N-phenyl-2-pyridincarboxamide-1-oxide as a ligand with Cu2O in Ullmann type C-N bond formations between aryl halides and N-heteroaryls in common solvents, such as MeCN, DMF, and DMSO at 82-120 °C has been successfully demonstrated. The ligand is effective when only 4% equiv is used relative to the substrate. The reaction provided the corresponding products in coupling of electron-rich, electron poor, and ortho-substituted aryl halides, including ortho aryl-chlorides, in good to very good yields. N-arylation is selectively preferred at the benzyl position when ortho-halide benzyl bromide is reacted with one equivalent of pyrazole. However, di-N-arylation is achieved in very high yields when 2.5 equiv of pyrazole is used, providing a stoichiometric control over the coupling reaction.
- Damkaci, Fehmi,Alawaed, Abdulkhaliq,Vik, Erik
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supporting information
p. 2197 - 2200
(2016/05/02)
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- Harnessing the pyrroloquinoxaline scaffold for FAAH and MAGL interaction: Definition of the structural determinants for enzyme inhibition
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This paper describes the development of piperazine and 4-aminopiperidine carboxamides/carbamates supported on a pharmacogenic pyrroloquinoxaline scaffold as inhibitors of the endocannabinoid catabolizing enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Structure-activity relationships and molecular modelling studies allowed the definition of the structural requirements for dual FAAH/MAGL inhibition and led to the identification of a small set of derivatives (compounds 5e, i, k, m) displaying a balanced inhibitory profile against both enzymes, with compound 5m being the frontrunner of the subset. Favorable calculated physico-chemical properties suggest further investigation for specific analogues.
- Brindisi, Margherita,Brogi, Simone,Maramai, Samuele,Grillo, Alessandro,Borrelli, Giuseppe,Butini, Stefania,Novellino, Ettore,Allarà, Marco,Ligresti, Alessia,Campiani, Giuseppe,Di Marzo, Vincenzo,Gemma, Sandra
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p. 64651 - 64664
(2016/07/23)
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- Design, Synthesis and Antimalarial Activity of Some New minoalcoholpyrrolo[ 1,2-A]quinoxaline Derivatives
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Following our search for antimalarial compounds, novel series of piperazinylalcohol pyrrolo 1,2-A]quinoxaline derivatives 1-2 were synthesized from 2-nitroaniline or 2-Amino-3 nitrophenol and tested for in vitro activity upon the intraerythrocytic stage of W2 and 3D7 Plasmodiu falciparum strains. Biological results showed good antimalarial activity with IC50 ranging fro 0.3 to 21.1 M. In attempting to investigate the large broad-spectrum antiprotozoal activities of thes pyrrolo[1,2-A]quinoxaline derivatives, their properties toward the promastigote form of Leishmani donovani were also investigated and revealed their selective antiplasmodial profile. In parallel, the i vitro cytotoxicity of these molecules was assessed on the human HepG2 cell line. Structure-Activit relationships of these new synthetic compounds are here discussed.
- Guillon, Jean,Moreau, Stéphane,Ronga, Luisa,Basmacyian, Louise,Cohen, Anita,Rubio, Sandra,Bentzinger, Guillaume,Savrimoutou, Solène,Azas, Nadine,Mullié, Catherine,Sonnet, Pascal
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p. 932 - 942
(2016/11/02)
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- Efficient synthesis of pyrrolo[1,2-: A] quinoxalines catalyzed by a Br?nsted acid through cleavage of C-C bonds
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An efficient and convenient one-pot domino reaction for the direct synthesis of pyrrolo[1,2-a]quinoxalines has been developed. This approach utilizes an imine formation reaction, SEAr reaction and cleavage of C-C bonds catalyzed by a Br?nsted acid. β-Diketones and β-keto esters are both well tolerated to give the corresponding products in moderate to excellent yields.
- Xie, Caixia,Feng, Lei,Li, Wanli,Ma, Xiaojun,Ma, Xinkun,Liu, Yihan,Ma, Chen
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supporting information
p. 8529 - 8535
(2016/09/28)
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- Synthesis, antifungal activity and QSAR of some novel carboxylic acid amides
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A series of novel aromatic carboxylic acid amides were synthesized and tested for their activities against six phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to good activity. Among them N-(2-(1H-indazol-1-yl)phenyl)-2-(trifluoromethyl)benzamide (3c) exhibited the highest antifungal activity against Pythium aphanidermatum (EC50 = 16.75 μg/mL) and Rhizoctonia solani (EC50 = 19.19 μg/mL), compared to the reference compound boscalid with EC50 values of 10.68 and 14.47 μg/mL, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were employed to develop a three-dimensional quantitative structure-activity relationship model for the activity of the compounds. In the molecular docking, a fluorine atom and the carbonyl oxygen atom of 3c formed hydrogen bonds toward the hydroxyl hydrogens of TYR58 and TRP173.
- Du, Shijie,Lu, Huizhe,Yang, Dongyan,Li, Hong,Gu, Xilin,Wan, Chuan,Jia, Changqing,Wang, Mian,Li, Xiuyun,Qin, Zhaohai
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p. 4071 - 4087
(2015/05/13)
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- Synthesis, antifungal activity and structure-activity relationships of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides
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A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.
- Du, Shijie,Tian, Zaimin,Yang, Dongyan,Li, Xiuyun,Li, Hong,Jia, Changqing,Che, Chuanliang,Wang, Mian,Qin, Zhaohai
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p. 8395 - 8408
(2015/05/20)
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- Gold(I)/chiral br??nsted acid catalyzed enantioselective hydroamination-hydroarylation of alkynes: The effect of a remote hydroxyl group on the reactivity and enantioselectivity
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The catalytic enantioselective hydroamination-hydroarylation of alkynes under the catalysis of (R3P)AuMe/(S)-3,3a?2-bis(2,4,6-triisopropylphenyl)-1,1a?2-bi-naphthyl-2,2a?2-diyl hydrogenphosphate ((S)-TRIP) is reported. The alkyne was reacted with a range of pyrrole-based aromatic amines to give pyrrole-embedded aza-heterocyclic scaffolds bearing a quaternary carbon center. The presence of a hydroxyl group in the alkyne tether turned out to be very crucial for obtaining products in high yields and enantioselectivities. The mechanism of enantioinduction was established by carefully performing experimental and computational studies.
- Shinde, Valmik S.,Mane, Manoj V.,Vanka, Kumar,Mallick, Arijit,Patil, Nitin T.
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supporting information
p. 975 - 979
(2015/02/05)
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- Ligand-free copper nanoparticle promoted N-arylation of azoles with aryl and heteroaryl iodides
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A relatively mild, efficient, and inexpensive method for the nucleophilic aromatic substitution of the N-H heterocycles with various aryl and heteroaryl iodides using copper nanoparticles (Cu-NP) is reported. The coupling reaction has been successfully ac
- Pai, Gita,Chattopadhyay, Asoke P.
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supporting information
p. 941 - 944
(2015/03/03)
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- New ligands for copper-catalyzed C-N coupling reactions at gentle temperature
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Pyridin-2-ol-N-oxide was designed as an efficient ligand for the coupling reaction of aryl iodides, aryl bromides and aryl chlorides, respectively, with primary amines, cyclic secondary amines or N-containing heterocycles at room or moderate temperature. The catalytic system showed great functional groups tolerance and excellent selective reactivity.
- Su, Jinyue,Qiu, Yatao,Jiang, Sheng,Zhang, Dayong
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supporting information
p. 685 - 688
(2014/10/15)
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- Ligand-free copper nanoparticle promoted N-arylation of azoles with aryl and heteroaryl iodides
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A relatively mild, efficient, and inexpensive method for the nucleophilic aromatic substitution of the N-H heterocycles with various aryl and heteroaryl iodides using copper nanoparticles (Cu-NP) is reported. The coupling reaction has been successfully ac
- Pai, Gita,Chattopadhyay, Asoke P.
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supporting information
p. 941 - 944
(2014/02/14)
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- H8-BINOL chiral imidodiphosphoric acids catalyzed enantioselective synthesis of dihydroindolo-/-pyrrolo[1,2- a ]quinoxalines
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The first enantioselective synthesis of 5,6-dihydroindolo[1,2-a]quinoxalines is achieved by using a newly developed H8-BINOL-type imidodiphosphoric acid catalyst with low catalyst loading through efficient Pictet-Spengler-type reactions of indolyl anilines with ketones. This methodology also generates phenyl-4,5-dihydropyrrolo[1,2-a]quinoxalines with high yields and excellent enantioselectivities. Moreover, this method was utilized to synthesize an HIV-1 inhibitor with high yield and good enantioselectivity through a one-step procedure.
- Fan, Yan-Sen,Jiang, Yi-Jun,An, Dong,Sha, Di,Antilla, Jon C.,Zhang, Suoqin
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supporting information
p. 6112 - 6115
(2015/01/09)
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- Design, synthesis and biological evaluation of novel 4- alkapolyenylpyrrolo[1,2-a]quinoxalines as antileishmanial agents - Part III
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A series of new 4-alkapolyenylpyrrolo[1,2-a]quinoxaline derivatives, original and structural analogues of alkaloid chimanine B and of previously described 4-alkenylpyrrolo[1,2-a]quinoxalines, was synthesized in good yields using efficient palladium-catalyzed Suzuki-Miyaura cross-coupling reactions. These new compounds were tested for in vitro antiparasitic activity upon three Leishmania spp. strains. Biological results showed activity against the promastigote forms of L. major, L. mexicana and L. donovani with IC50 ranging from 1.2 to 14.7 μM. In attempting to investigate if our pyrrolo[1,2-a]quinoxaline derivatives are broad-spectrum antiprotozoal compounds activities toward one Trypanosoma brucei brucei strain and the W2 and 3D7 Plasmodium falciparum strains were also investigated. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Structure-activity relationships of these new synthetic compounds are here discussed.
- Ronga, Luisa,Del Favero, Marco,Cohen, Anita,Soum, Claire,Le Pape, Patrice,Savrimoutou, Solène,Pinaud, No?l,Mullié, Catherine,Daulouede, Sylvie,Vincendeau, Philippe,Farvacques, Natacha,Agnamey, Patrice,Pagniez, Fabrice,Hutter, Sébastien,Azas, Nadine,Sonnet, Pascal,Guillon, Jean
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p. 378 - 393
(2014/06/09)
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- Synthesis and in vitro evaluation of 4-trichloromethylpyrrolo[1,2-A] quinoxalines as new antiplasmodial agents
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Thanks to a preliminary in vitro screening of several CCl 3-substituted-nitrogen containing heterocycles belonging to our chemical library, the 2-trichloromethylquinoxaline scaffold appeared to be of potential interest for developing new antiplasmodial agents. Then, combining these experimental results to the antimalarial properties reported for various pyrrolo[1,2-A]quinoxaline derivatives, an original series of fifteen 7-substituted-4-trichoromethylpyrrolo[1,2-A]quinoxalines was synthesized in a 4 to 5 reaction steps pathway. All molecules were evaluated in vitro toward both their antiplasmodial activity on the K1 multi-resistant Plasmodium falciparum strain and their cytotoxicity on the HepG2 human cell line. Thus, 3 hit molecules were identified, displaying IC50 values in the micromolar range and low cytotoxicity values, reaching good selectivity indexes, in comparison with the reference drugs chloroquine and doxycycline. Structure-activity relationship studies showed that the pyrrolo[1,2-A] quinoxaline scaffold can support selective antiplasmodial activity when substituted at position 4 by a CCl3 group. However, substitution at position 7 of the same scaffold is neither beneficial for cytotoxicity nor favourable for the solubility in the biological media.
- Primas, Nicolas,Suzanne, Peggy,Verhaeghe, Pierre,Hutter, Sébastien,Kieffer, Charline,Laget, Michèle,Cohen, Anita,Broggi, Julie,Lancelot, Jean-Charles,Lesnard, Aurélien,Dallemagne, Patrick,Rathelot, Pascal,Rault, Sylvain,Vanelle, Patrice,Azas, Nadine
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- Discovery of pyrrolo-benzo-1,4-diazines as potent Nav1.7 sodium channel blockers
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A series of pyrrolo-benzo-1,4-diazine analogs have been synthesized and displayed potent Nav1.7 inhibitory activity and moderate selectivity over Nav1.5. The syntheses, structure-activity relationships, and selected pharmacokinetic data of these analogs are described. Compound 41 displayed anti-nociceptive efficacy in the rat CFA pain model at 100 mpk oral dosing.
- Ho, Ginny D.,Tulshian, Deen,Bercovici, Ana,Tan, Zheng,Hanisak, Jennifer,Brumfield, Stephanie,Matasi, Julius,Heap, Charles R.,Earley, William G.,Courneya, Brandy,Jason Herr,Zhou, Xiaoping,Bridal, Terry,Rindgen, Diane,Sorota, Steve,Yang, Shu-Wei
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p. 4110 - 4113
(2014/11/07)
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- Squaric acid catalyzed simple synthesis of N-substituted pyrroles in green reaction media
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An operationally simple and efficient protocol for squaric acid catalyzed synthesis of N-substituted pyrroles via the reaction of 2,5- dimethoxytetrahydrofuran and 2,5-hexandione with aryl amines in green reaction media (water, deep eutectic solvent, and polyethylene glycol) under ultrasound irradiation or thermal conditions in good to excellent yields has been developed.
- Azizi, Najmadin,Davoudpour, Anahita,Eskandari, Farshid,Batebi, Ehlham
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p. 405 - 409
(2013/05/09)
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- A recyclable magnetic nanoparticles supported antimony catalyst for the synthesis of N-substituted pyrroles in water
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A new magnetic nanoparticle-supported antimony catalyst was prepared and evaluated as a recoverable catalyst for Clauson-Kaas reaction. The reaction proceeds efficiently in aqueous medium to give the corresponding N-substituted pyrroles in high yield. The immobilized catalyst could be easily recovered by magnetic separation and recycled for six times without significant loss of its catalytic activity.
- Ma, Fei-Ping,Li, Pei-He,Li, Bao-Le,Mo, Li-Ping,Liu, Ning,Kang, Hui-Jun,Liu, Ya-Nan,Zhang, Zhan-Hui
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- Two Component Recyclable Heterogeneous Catalyst, Process for Preparation Thereof and its Use for Preparation of Amines
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The invention describes the development of highly efficient, recyclable two component system, CuAl-hydrotalcite/rac 1,1′-Binaphthalene-2,2′-diol catalytic system for the N-alkylation of electron deficient aryl chlorides in presence of potassium carbonate as a base at room temperature in 3-6 h, wherein the process is provided for the preparation of various secondary amines via C—N coupling reaction of aliphatic amines(aliphatic open chain, acyclic, benzyl amines and heterocyclic amines) with various aryl chlorides.
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Page/Page column 8
(2012/01/13)
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- Ligands for copper-catalyzed C-N bond forming reactions with 1 Mol% CuBr as catalyst
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Several new ligands were designed to promote copper-catalyzed Ullman C-N coupling reactions. In this group, 8-hydroxyquinolin-N-oxide was found to serve as a superior ligand for CuBr-catalyzed coupling reactions of aryl iodides, bromides, and chlorides with aliphatic amines and N-heterocycles under a low catalyst loading (1% [Cu] mol). Reactions with the inexpensive catalytic system display a high functional group tolerance as well as excellent chemoselectivity.
- Yang, Kai,Qiu, Yatao,Li, Zheng,Wang, Zhaoyang,Jiang, Sheng
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experimental part
p. 3151 - 3159
(2011/06/23)
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- New strategy for the synthesis of N-aryl pyrroles: Cu-catalyzed C-N cross-coupling reaction of trans-4-hydroxy-l-proline with aryl halides
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trans-4-Hydroxy-l-proline is used for the first time as an effective nucleophilic coupling partner with aryl halides mediated by copper iodide with Cs2CO3 as the base and DMSO as the solvent. Utilizing this protocol cross-coupling of trans-4-hydroxy-l-proline with a wide variety of substituted aryl halides to produce N-aryl pyrroles in moderate to good yields.
- Reddy, V. Prakash,Kumar, A. Vijay,Rao, K. Rama
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experimental part
p. 777 - 780
(2011/03/21)
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- Unique chemoselective Clauson-Kass reaction of substituted aniline catalyzed by MgI2 etherate
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Clauson-Kass reaction of various substituted aniline, primary aryl amide, and sufonyl amide with 2,5-dimethoxytetrahydrofuran was realized in the presence of 10 mol % of MgI2 etherate in a mild, efficient, and highly chemoselective manner. Iodide counterion and solvents (i.e., MeCN) played the critical roles for the unique reactivity of this catalytic system.
- Zhang, Xingxian,Shi, Junchen
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experimental part
p. 898 - 903
(2011/03/19)
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- Scandium triflate-catalysed synthesis of N-substituted pyrroles from amine and 2,5-dimethoxytetrahydrofuran
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The Clauson-Kass pyrrole synthesis catalysed by scandium triflate afforded N-substituted 2- and 3-unsubstituted pyrroles with yields ranged from good to excellent. Aromatic amines, heteroaomatic amines, 4-methylbenzenesulfonamide and 2-chlorobenzamide are good substrates in this transformation.
- Zuo, Bing,Chen, Jiuxi,Liu, Miaochang,Ding, Jinchang,Wu, Huayue,Su, Weike
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experimental part
p. 14 - 16
(2009/09/25)
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- New ferrocenic pyrrolo[1,2-a]quinoxaline derivatives: Synthesis, and in vitro antimalarial activity
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Following our search for antimalarial compounds, novel series of ferrocenic pyrrolo[1,2-a]quinoxaline derivatives 1-2 were synthesized from various substituted nitroanilines and tested for in vitro activity upon the erythrocytic development of Plasmodium falciparum strains with different chloroquine-resistance status. The pyrrolo[1,2-a]quinoxalines 1 were prepared in 6-8 steps through a regioselective palladium-catalyzed monoamination by coupling 4-chloropyrrolo[1,2-a]quinoxalines with 1,3-bis(aminopropyl)piperazine or -methylamine using Xantphos as the ligand. The ferrocenic bispyrrolo[1,2-a]quinoxalines 2 were prepared by reductive amination of previously described bispyrrolo[1,2-a]quinoxalines 9 with ferrocene-carboxaldehyde, by treatment with NaHB(OAc)3. The best results were observed with ferrocenic pyrrolo[1,2-a]quinoxalines linked by a bis(3-aminopropyl)piperazine. Moreover, it was observed that a methoxy group on the pyrrolo[1,2-a]quinoxaline nucleus and no substitution on the terminal N-ferrocenylmethylamine function enhanced the pharmacological activity. Selected compounds 1b, 1f-h, 1l and 2a were tested for their ability to inhibit β-haematin formation, the synthetic equivalent of hemozoin, by using the HPIA (heme polymerization inhibitory activity) assay. Of the tested compounds, only 2a showed a β-haematin formation inhibition, but no inhibition of haem polymerization was observed with the other selected ferrocenic monopyrrolo[1,2-a]quinoxaline derivatives 1b, 1f-h and 1l, as the IC50 values were superior to 10 equivalents.
- Guillon, Jean,Moreau, Stephane,Mouray, Elisabeth,Sinou, Veronique,Forfar, Isabelle,Fabre, Solene Belisle,Desplat, Vanessa,Millet, Pascal,Parzy, Daniel,Jarry, Christian,Grellier, Philippe
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body text
p. 9133 - 9144
(2009/04/11)
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- PHENYL PYRROLE AMINOGUANIDINE DERIVATIVES
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The present invention relates to phenyl pyrrole aminoguanidine derivatives of the general formula (I): (I) including tautomeric forms thereof, wherein n is 1, 2 or 3; or a pharmaceutically acceptable salt thereof. The present invention further relates to
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Page/Page column 37
(2008/06/13)
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- Synthesis of omeprazole analogues and evaluation of these as potential inhibitors of the multidrug efflux pump NorA of Staphylococcus aureus
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A series of 11 pyrrolo[1,2-α]quinoxaline derivatives, 1a to 1k, sharing structural analogies with omeprazole, a eukaryotic efflux pump inhibitor (EPI) used as an antiulcer agent, was synthesized. Their inhibitory effect was evaluated using Staphylacoccus aureus strain SA-1199B overexpressing NorA. By determinations of the MIC of norfloxacin in the presence of these EPIs devoid of intrinsic antibacterial activity and used at 128 μg/ml, and by the checkerboard method, compound 1e (MIC decrease, 16-fold; fractional inhibitory concentration index [ΣFIC], 0.18) appeared to be more active than compounds 1b to 1d, reserpine, and omeprazole (MIC decrease, eightfold; ΣFIC, 0.31), followed by compounds 1a and 1f (MIC decrease, fourfold; ΣFIC, 0.37) and 1g to 1k (MIC decrease, twofold; ΣFIC, 0.50 to 0.56). By time-kill curves combining norfloxacin (1/4 MIC) and the most efficient EPIs (128 μg/ml), compound 1e persistently restored the bactericidal activity of norfloxacin (inoculum reduction, 3 log10 CFU/ml at 8 and 24 h), compound If led to a delayed but progressive decrease in the number of viable cells, and compounds 1b to 1d and omeprazole acted synergistically (inoculum reduction, 3 log10 CFU/ml at 8 h but further regrowth), while compound 1a and reserpine slightly enhanced norfloxacin activity. The bacterial uptake of norfloxacin monitored by high-performance liquid chromatography confirmed that compounds 1a to 1f increased antibiotic accumulation, as did reserpine and omeprazole. Since these EPIs did not disturb the Δψ and ΔpH, they might directly interact with the pump. A structure-activity relationships study identified the benzimidazole nucleus of omeprazole as the main structural element involved in efflux pump inhibition and highlighted the critical role of the chlorine substituents in the stability and efficiency of compounds 1e to 1f. However, further pharmacomodulation is required to obtain therapeutically applicable derivatives. Copyright
- Vidaillac, Celine,Guillon, Jean,Arpin, Corinne,Forfar-Bares, Isabelle,Ba, Boubakar B.,Grellet, Jean,Moreau, Stephane,Caignard, Daniel-Henri,Jarry, Christian,Quentin, Claudine
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p. 831 - 838
(2007/10/03)
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- Synthesis, analytical behaviour and biological evaluation of new 4-substituted pyrrolo[1,2-a]quinoxalines as antileishmanial agents
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An original series of 4-substituted pyrrolo[1,2-a]quinoxaline derivatives, new structural analogues of Galipea species quinoline alkaloids, was synthesized from various substituted 2-nitroanilines via multistep heterocyclizations and tested for in vitro antiparasitic activity upon Leishmania amazonensis and Leishmania infantum strains. Structure-activity relationships enlighten the importance of the 4-substituted alkenyl side chain on the pyrrolo[1,2-a]quinoxaline moiety to modulate the antileishmanial activity.
- Guillon, Jean,Forfar, Isabelle,Mamani-Matsuda, Maria,Desplat, Vanessa,Saliege, Marion,Thiolat, Denis,Massip, Stephane,Tabourier, Anais,Leger, Jean-Michel,Dufaure, Benoit,Haumont, Gilbert,Jarry, Christian,Mossalayi, Djavad
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p. 194 - 210
(2008/02/01)
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- Method for arylating aza-heterocycles with activated aromatic compounds in the presence of caesium carbonate
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The invention concerns a process for the preparation of N-aryl-aza-heterocycles of the general formula I by reaction of aza-heterocycles with activated aryl halides with use of caesium carbonate without addition of further catalysts at room temperature.
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Page column 8
(2008/06/13)
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- Synthesis, Antimalarial Activity, and Molecular Modeling of New Pyrrolo[1,2-a]quinoxalines, Bispyrrolo[1,2-a]quinoxalines, Bispyrido[3,2-e]pyrrolo[1,2-a]pyrazines, and Bispyrrolo[1,2-a]thieno[3,2-e]pyrazines
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Three pyrrolo[1,2-a]quinoxalines, 15 bispyrrolo[1,2-a]quinoxalines, bispyrido[3,2-e]pyrrolo[1,2-a]pyrazines, and bispyrrolo[1,2-a]thieno[3,2-e]pyrazines were synthesized from various substituted nitroanilines or nitropyridines and tested for their in vitro activity upon the erythrocytic development of Plasmodium falciparum strains with different chloroquine-resistance status. Bispyrrolo[1,2-a]quinoxalines showed superior antimalarial activity with respect to monopyrrolo[1,2-a]quinoxalines. The best activity was observed with bispyrrolo[1,2-a]quinoxalines linked by a bis(3-aminopropyl)piperazine. Moreover, it was observed that the presence of a methoxy group on the pyrrolo[1,2-a]quinoxaline nucleus increased the pharmacological activity. Drug effects upon β-hematin formation were assayed and showed similar or higher inhibitory activities than CQ. A possible mechanism of interaction implicating binding of pyrroloquinoxalines to β-hematin was supported by molecular modeling.
- Guillon, Jean,Grellier, Philippe,Labaied, Mehdi,Sonnet, Pascal,Léger, Jean-Michel,Déprez-Poulain, Rébecca,Forfar-Bares, Isabelle,Dallemagne, Patrick,Lema?tre, Nicolas,Péhourcq, Fabienne,Rochette, Jacques,Sergheraert, Christian,Jarry, Christian
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p. 1997 - 2009
(2007/10/03)
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- Reductive one batch synthesis of N-substituted pyrrolidines from primary amines and 2,5-dimethoxytetrahydrofuran
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The construction of the pyrrolidine ring about a nitrogen of a primary amine by a reductive condensation reaction using 2,5- dimethoxytetrahydrofuran and sodium borohydride in acidic water medium is described. The reaction is fast, affords good to excellent yields and appears insensitive to electron effects and severe steric hindrance; it is found to be compatible with a large variety of aryl substituents, including nitro and oxo groups. The reaction allows the introduction of two deuterium atoms, with label conservation, in both the α-positions of the pyrrolidine ring by the use of sodium borodeuteride instead of sodium borohydride.
- Verardo, Giancarlo,Dolce, Anna,Toniutti, Nicoletta
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- Synthesis of new pyrrolo[l,2-a]quinoxalines: Potential non-peptide glucagon receptor antagonists
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Synthesis of new pyrrolo[1,2-a]quinoxaline derivatives was achieved starting from various nitroanilines or orthophenyle-nediamines. Their affinity towards glucagon receptors was evaluated. Elsevier, Paris.
- Guillon, Jean,Dallemagne, Patrick,Pfeiffer, Bruno,Renard, Pierre,Manechez, Dominique,Kervran, Alain,Rault, Sylvain
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p. 293 - 308
(2007/10/03)
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- Synthesis and antituberculosis activity of new phenylpyrrolo[1,2-a] quinoxalinylpyrrole carboxylic acid derivatives
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During the course of our work on the synthesis and screening of new drugs for tuberculosis, we have identified three new phenylpyrrolo[1,2-a]quinoxalinylpyrrole carboxylic acid derivatives which inhibited in-vitro Mycobacterium tuberculosis H37Rv; 97-98% inhibition at 12.5 μg mL-1.
- Guillon,Dumoulin,Dallemagne,Reynolds,Rault
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- Spiro(pyrrolo (1,2-A)quinoxalines)
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Spiro[pyrrolo(1,2-a)quinoxalines] and their physiologically tolerable acid addition salts possessing anticonvulsant and central nervous system depressant properties, and a process for their preparation are described.
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