- New benzimidazolium N-heterocyclic carbene precursors and their related Pd-NHC complex PEPPSI-type: Synthesis, structures, DFT calculations, biological activity, docking study, and catalytic application in the direct arylation
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New benzhydryl-5,6-dimethyl-(3-methylbenzyl)benzimidazolium salt as N-heterocyclic carbene precursors and their related new Pd-NHC complex PEPPSI-type with the general formula [PdBr2(NHC)(pyridine)] were prepared and theoretically studied. Quan
- ?zdemir, ?smail,?zdemir, Nam?k,Bensouici, Chawki,Benzerka, Saida,Boulebd, Houssem,Gürbüz, Nevin,Khiri-Meribout, Naima,Sandeli, Abd El-Krim
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- 1,3-Dioxane Functionalized Pd-PEPPSI Catalyst for Direct Arylation of Heteroaromatics
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A series of benzimidazolium salts (1a-d) and their Pd-PEPPSI complexes (pyridine-enhanced precatalyst preparation, stabilization, and initiation) (2a-d) were prepared to catalyze the direct arylation of heteroaromatics (2-acetylthiophene and 2-furaldehyde) with various aryl bromides. The structures of all isolated compounds were elucidated based on spectroscopic methods (1H and 13C NMR, FT-IR and LC-MS spectroscopy). Under optimized reaction conditions, C5-arylated products were obtained in moderate to excellent yields in the direct arylation of heteroaromatics.
- Ulu, ?znur Do?an
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- Synthesis of [PdBr2(benzimidazole-2-ylidene)(pyridine)] complexes and their catalytic activity in the direct C[sbnd]H bond activation of 2-substituted heterocycles
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A series of unsymmetrical 1,3-disubstituted benzimidazolium chlorides, 2a-f, having two nitrogen atoms substituted by various alkyl groups were synthesized as N-heterocyclic carbene (NHC) precursors in high yields. The benzimidazolium salts are readily co
- Lasmari, Sarra,Gürbüz, Nevin,Boulcina, Raouf,?zdemir, Nam?k,?zdemir, ?smail
-
-
- Synthesis of Quinoxaline-Linked Bis(Benzimidazolium) Salts and Their Catalytic Application in Palladium-Catalyzed Direct Arylation of Heteroarenes
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Abstract: In this study, quinoxaline-linked bis(benzimidazolium) salts were synthesized as bis-N-heterocyclic carbene (NHC) precursors. These bis(NHC) precursors were used as multidentate ligands for the construction of bi(hetero)aryls by palladium-cataly
- ?zdemir, ?smail,?ahan, Mehmet Hanifi,Dü?ünceli, Serpil Demir,Kalo?lu, Murat
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- Synthesis, structures, DFT calculations, and catalytic application in the direct arylation of five-membered heteroarenes with aryl bromides of novel palladium-N-heterocyclic carbene PEPPSI-type complexes
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A new series of Pd-catalysts based on an N-heterocyclic carbene PEPPSI-type ligand (PEPPSI = pyridine enhanced precatalyst preparation stabilization and initiation) with the general formula [Pd(ii)Br2(NHC)(pyridine)] was synthesized and fully characterize
- ?zdemir, ?smail,?zdemir, Nam?k,Benzerka, Saida,Boulebd, Houssem,Gürbüz, Nevin,Khiri-Meribout, Naima,el-Krim Sandeli, Abd
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p. 17878 - 17892
(2021/10/12)
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- Carbon–Carbon Bond Formation for the Synthesis of 5-Aryl-2-Substituted Furans Catalyzed by K3[Fe(CN)6]
-
An efficient method for the carbon–carbon bond formation at C-5 position of 2-substituted furans to provide a range of π-diverse 5-aryl-2-substituted furan derivatives in 58–80% yield has been reported. The method employs several advantages such as use of catalytic amount of K3[Fe(CN)6] under mild conditions and short reaction time with high yields. Also, a variety of anilines with a variety of functional groups can be employed for the synthesis of 5-aryl-2-substituted furans. Graphic Abstract: [Figure not available: see fulltext.]
- Ambika,Singh, Pradeep Pratap
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- Synthesis of novel benzimidazoles and benzothiazoles via furan-2-carboxaldehydes, o-phenylenediamines, and 2-aminothiophenol using Cu(II) Schiff-base@SiO2 as a nanocatalyst
-
2-(5-Substituted phenyl)furan-2-carboxaldehyde derivatives were prepared by using an efficient copper(II) complex of tetradentate Schiff-base ligand immobilized onto silica as a heterogeneous nanocatalyst [Cu(II) Schiff-base@SiO2] (5.0?mol%) using anilines, sodium nitrite, and furan-2-carboxaldehyde. Furthermore, attractive di-heteroaryl benzo-fused systems such as benzimidazole and benzothiazole derivatives were synthesized using this nanocatalyst (5.0?mol%) via the reaction of o-phenylenediamines and 2-aminothiophenol with 2-(5-substituted phenyl)furan-2-carboxaldehydes in EtOH. The catalyst was characterized by Fourier transform infrared (FT-IR), field emission scanning electron microscope (FESEM), energy-dispersive X-ray spectroscopy (EDX), X-ray powder diffraction (XRD), and inductively coupled plasma (ICP) techniques. The advantages of the present catalytic system are short reaction times, mild conditions, good to excellent yields, and low amount of nanocatalyst. Moreover, to the best of our knowledge, this is the first time of using the same catalyst in two steps including synthesis of 2-(5-substituted phenyl)furan-2-carboxaldehyde and benzimidazole or benzothiazole derivatives. In addition, the synthesized catalyst was recycled very well and reused several times without significant loss of its catalytic activity.
- Sharghi, Hashem,Mashhadi, Elahe,Aberi, Mahdi,Aboonajmi, Jasem
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- Novel Furan-2-yl-1 H-pyrazoles Possess Inhibitory Activity against α-Synuclein Aggregation
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A series of novel furan-2-yl-1H-pyrazoles and their chemical precursors were synthesized and evaluated for their effectiveness at disrupting α-synuclein (α-syn) aggregation in vitro. The compounds were found to inhibit α-syn aggregation with efficacy comp
- Ryan, Philip,Xu, Mingming,Jahan, Kousar,Davey, Andrew K.,Bharatam, Prasad V.,Anoopkumar-Dukie, Shailendra,Kassiou, Michael,Mellick, George D.,Rudrawar, Santosh
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p. 2303 - 2315
(2020/11/05)
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- Palladium-carbene catalyzed direct arylation of five-membered heteroaromatics
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Due to the industrial importance of bi(hetero)arenes, the synthesis of these compounds by homogeneous Pd-catalyzed direct arylation is an important research topic in modern organic chemistry. In this study, PEPPSI-type, (PEPPSI = Pyridine Enhanced Precatalyst Preparation Stabilization and Initiation), new Pd-catalysts with N-heterocyclic carbene ligand were synthesized, and they were used as catalysts in the synthesis of bi(hetero)arenes by direct arylation process. The structures of Pd-carbene complexes were elucidated by different spectroscopic and analytical techniques such as NMR, FT-IR and elemental analysis. The more detailed structural characterization of one of the complexes was determined by single-crystal X-ray diffraction study. Pd-carbene complexes were used as effective catalysts in the direct arylation of five-membered heteroaromatics such as thiophene, furan and thiazole derivatives with (hetero)aryl bromides for 1 h, in the presence of 1 mol% of catalyst loading, and successful results were obtained.
- ?zdemir, ?smail,?zdemir, Nam?k,Kalo?lu, Murat,Kalo?lu, Nazan,Y?ld?r?m, ?lkay
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- Virtual screening-driven discovery of dual 5-HT6/5-HT2A receptor ligands with pro-cognitive properties
-
A virtual screening campaign aimed at finding structurally new compounds active at 5-HT6R provided a set of candidates. Among those, one structure, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (1, 5-HT6R Ki = 91 nM), was selected as a hit for further optimization. As expected, the chemical scaffold of selected compound was significantly different from all the serotonin receptor ligands published to date. Synthetic efforts, supported by molecular modelling, provided 43 compounds representing different substitution patterns. The derivative 42, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (5-HT6R Ki = 25, 5-HT2AR Ki = 32 nM), was selected as a lead and showed a good brain/plasma concentration profile, and it reversed phencyclidine-induced memory impairment. Considering the unique activity profile, the obtained series might be a good starting point for the development of a novel antipsychotic or antidepressant with pro-cognitive properties.
- Staroń, Jakub,Kurczab, Rafa?,Warszycki, Dawid,Sata?a, Grzegorz,Krawczyk, Martyna,Bugno, Ryszard,Lenda, Tomasz,Popik, Piotr,Hogendorf, Adam S.,Hogendorf, Agata,Dubiel, Krzysztof,Mat?oka, Miko?aj,Moszczyński-P?tkowski, Rafa?,Pieczykolan, Jerzy,Wieczorek, Maciej,Zajdel, Pawe?,Bojarski, Andrzej J.
-
supporting information
(2019/11/28)
-
- Novel N-Substituted oseltamivir derivatives as potent influenza neuraminidase inhibitors: Design, synthesis, biological evaluation, ADME prediction and molecular docking studies
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The discovery of novel potent neuraminidase (NA) inhibitors remains an attractive approach for treating infectious diseases caused by influenza. In this study, we describe the design and synthesis of novel N-substituted oseltamivir derivatives for probing the 150-cavity which is nascent to the activity site of NA. NA inhibitory studies showed that new derivatives demonstrated the inhibitory activity with IC50 values at nM level against NA of a clinical influenza virus strain. Moreover, the in silico ADME predictions showed that the selected compounds had comparable properties with oseltamivir carboxylate, which demonstrated the druggablity of these derivatives. Furthermore, molecular docking studies showed that the most potent compound 6f and 10i could adopt different modes of binding interaction with NA, which may provide novel solutions for treating oseltamivir-resistant influenza. Based on the research results, we consider that compounds 6f and 10i have the potential for further studies as novel antiviral agents.
- Ye, Jiqing,Yang, Xiao,Xu, Min,Chan, Paul Kay-sheung,Ma, Cong
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supporting information
(2019/09/06)
-
- Metal-Free Aerobic Oxidative Selective C-C Bond Cleavage in Heteroaryl-Containing Primary and Secondary Alcohols
-
A transition-metal-free aerobic oxidative selective C-C bond-cleavage reaction in primary and secondary heteroaryl alcohols is reported. This reaction was highly efficient and tolerated various heteroaryl alcohols, generating a carboxylic acid derivative and a neutral heteroaromatic compound. Experimental studies combined with density functional theory calculations revealed the mechanism underlying the selective C-C bond cleavage. This strategy also provides an alternative simple approach to carboxylation reaction.
- Xia, Anjie,Qi, Xueyu,Mao, Xin,Wu, Xiaoai,Yang, Xin,Zhang, Rong,Xiang, Zhiyu,Lian, Zhong,Chen, Yingchun,Yang, Shengyong
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supporting information
(2019/05/07)
-
- Discovery of (5-Phenylfuran-2-yl)Methanamine derivatives as new human sirtuin 2 Inhibitors
-
Human sirtuin 2 (SIRT2), a member of the sirtuin family, has been considered as a promising drug target in cancer, neurodegenerative diseases, type II diabetes, and bacterial infections. Thus, SIRT2 inhibitors have been involved in effective treatment strategies for related diseases. Using previously established fluorescence-based assays for SIRT2 activity tests, the authors screened their in-house database and identified a compound, 4-(5-((3-(quinolin-5-yl)ureido)methyl) furan-2-yl)benzoic acid (20), which displayed 63 ± 5% and 35 ± 3% inhibition against SIRT2 at 100 μM and 10 μM, respectively. The structure-activity relationship (SAR) analyses of a series of synthesized (5-phenylfuran-2-yl)methanamine derivatives led to the identification of a potent compound 25 with an IC50 value of 2.47 μM, which is more potent than AGK2 (IC50 = 17.75 μM). Meanwhile, 25 likely possesses better water solubility (cLogP = 1.63 and cLogS = ?3.63). Finally, the molecular docking analyses indicated that 25 fitted well with the induced hydrophobic pocket of SIRT2.
- Wang, Lijiao,Li, Chao,Chen, Wei,Song, Chen,Zhang, Xing,Yang, Fan,Wang, Chen,Zhang, Yuanyuan,Qian, Shan,Wang, Zhouyu,Yang, Lingling
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- Access to Densely Functionalized Chalcone Derivatives with a 2-Pyridone Subunit via Pd/Cu-Catalyzed Oxidative Furan-Yne Cyclization of N -(2-Furanylmethyl) Alkynamides under Air
-
A protocol for synthesis of chalcone derivatives with a 2-pyridone subunit from N-(2-furanylmethyl) alkynamides is reported. This synthesis involves Pd/Cu-catalyzed oxidative furan-yne cyclization at room temperature in air and may proceed via nucleopalladation of the alkyne to form a vinylpalladium intermediate, with a furan ring acting as the nucleophile.
- Yang, Yongjie,Fei, ChengCheng,Wang, Kai,Liu, Bo,Jiang, Dingxin,Yin, Biaolin
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supporting information
p. 2273 - 2277
(2018/04/30)
-
- Small molecule near-infrared boron dipyrromethene donors for organic tandem solar cells
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Three furan fused boron dipyrromethenes (BODIPYs) with a CF3 group on the meso-carbon are synthesized as near-infrared absorbing materials for vacuum processable organic solar cells. The best single junction device reaches a short-circuit curre
- Li, Tian-Yi,Meyer, Toni,Ma, Zaifei,Benduhn, Johannes,Korner, Christian,Zeika, Olaf,Vandewal, Koen,Leo, Karl
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supporting information
p. 13636 - 13639
(2017/11/06)
-
- Antibacterial and antifungal properties of guanylhydrazones
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A series of novel guanylhydrazones were designed, synthesized and characterized. All the compounds were screened for their antibacterial and antifungal activity. Compounds 26 and 27 showed excellent antibacterial activities against Staphylococcus aureus A
- Ajda?i?, Vladimir,Lazi?, Jelena,Moji?evi?, Marija,?egan, Sandra,Nikodinovic-Runic, Jasmina,Opsenica, Igor M.
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p. 641 - 649
(2017/08/09)
-
- Discovery of selective protein arginine methyltransferase 5 inhibitors and biological evaluations
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Protein arginine methyltransferase 5 (PRMT5) is an important protein arginine methyltransferase that catalyzes the symmetric dimethylation of arginine resides on histones or non-histone substrate proteins. It has been thought as a promising target for many diseases, particularly cancer. Despite the potential applications of PRMT5 inhibitors in cancer treatment, very few of PRMT5i have been publicly reported. In this investigation, virtual screening and structure–activity relationship studies were carried out to discover novel PRMT5i, which finally led to the identification of a number of new PRMT5i. The most active compound, P5i-6, exhibited a considerable inhibitory potency against PRMT5 with an IC50 value of 0.57?μm, and a high selectivity for PRMT5 against other tested PRMTs. It displayed a very good antiviability activity against two colorectal cancer cell lines, HT-29 and DLD-1, and one hepatic cancer cell line, HepG2, in a sensitivity assay against 36 different cancer cell lines. Western blot assays indicated that P5i-6 selectively inhibited the symmetric dimethylations of H4R3 and H3R8 in DLD-1 cells. Overall, P5i-6 could be used as a chemical probe to investigate new functions of PRMT5 in biology and also served as a good lead compound for the development of new PRMT5-targeting therapeutic agents.
- Ji, Sen,Ma, Shuang,Wang, Wen-Jing,Huang, Shen-Zhen,Wang, Tian-Qi,Xiang, Rong,Hu, Yi-Guo,Chen, Qiang,Li, Lin-Li,Yang, Sheng-Yong
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p. 585 - 598
(2017/04/06)
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- RESIN COMPOSITION AND MOLDED ARTICLE
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The invention contains a resin and a near infrared fluorescent material which is one type or two or more types of compounds selected from General Formulas (I1) to (I4) and has a maximum fluorescence wavelength of 650 nm or longer. In Formulas, Ra and Rb, Rc and Rd, Rh and Ri, and Rj and Rk form rings together with the nitrogen atom to which Ra, Rc, Rh, and Rj are bonded; Re and Rf represent a halogen atom or an oxygen atom; each of Rl, Rm, Rn, and Ro independently represents a halogen atom, a C1-20 alkyl group, a C1-20 alkoxy group, an aryl group, or a heteroaryl group; Rg, Rr, and Rs represent a hydrogen atom or an electron withdrawing group; and each of Rp and Rq independently represents a hydrogen atom, a halogen atom, a C1-20 alkyl group, a C1-20 alkoxy group, an aryl group, or a heteroaryl group.
- -
-
Paragraph 0257
(2016/10/11)
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- A HIGH-THROUGHPUT ASSAY FOR IDENTIFYING SMALL MOLECULES THAT MODULATE AMP-ACTIVATED PROTEIN KINASE (AMPK)
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The present invention provides an in vitro method for identifying a compound that modulates adenosine monophosphate-activated protein kinase (AMPK) for the manufacture of a diagnostic or therapeutic agent. The present invention further provides an assay for identifying a compound that modulates AMPK.
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Page/Page column 62; 63
(2016/02/29)
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- Synthesis and biological evaluation of 2-phenylimino-5((5-phenylfuran-2-yl)methylene)thiazolidin-4-ones as IKK2 inhibitors
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In a search for novel molecules to treat inflammatory disorders, we identified several compounds with inhibitory action against the IKK2 enzyme using in silico methods. Based on the virtual hit of compounds 1 and 2, a novel series of 2-phenylimino-5((5-phenylfuran-2-yl)methylene)thiazolidin-4-one derivatives was designed, synthesized, and evaluated for IKK2 inhibitory activity. Among the synthesized derivatives, compounds 17f and 19f showed good IKK2 inhibitory potency, which have 4-carboxaminophenyl on the 2-furan ring and a methoxy group on the phenylimino moiety at the 2-position of the core structure. The most potent compound was 2-(2,4-dimethoxyphenyl)imino-5((5(4-carboxaminophenyl)furan-2-yl)methylene)thiazolidin-4-one (19f, IC50 = 0.94 μM), which represents a synergic effect of the two virtual hit compounds against IKK2. We also identified compounds showing inhibitory activities against interleukin (IL)-17, CCK-8, and tumor necrosis factor-alpha (TNF-α), which are NF-κB-dependent pro-inflammatory cytokine mediators.
- Kim, Hee Sook,Shin, Min Jae,Lee, Byungho,Oh, Kwang-Seok,Choo, Hyunah,Pae, Ae Nim,Roh, Eun Joo,Nam, Ghilsoo
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p. 2621 - 2626
(2015/11/16)
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- Synthesis and evaluation of arylfuryl-bis(indolyl)methanes as selective chromogenic and fluorogenic ratiometric receptors for mercury ion in aqueous solution
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A series of arylfuryl-bis(indolyl)methane derivatives were prepared in good yields by electrophilic substitution of indole with furyl aldehydes through a simple and mild hydrogensulfate-catalysed reaction and studied as chemosensors for transition metal cations by performing spectrophotometric and spectrofluorimetric titrations. Selective recognition of Hg2+ was achieved in organic aqueous mixture (CH3CN/H2O, 7:3) for the various receptors, with an easily detectable colour change from colourless to purple and also through a fluorescence quenching, making these compounds suitable for dual chromo- and fluorogenic ratiometric sensing of Hg 2+. The binding stoichiometry between the receptors and Hg 2+ was found to be 1:1. The binding process was also followed by 1H NMR titrations which corroborated the previous findings.
- Batista, Rosa M.F.,Costa, Susana P.G.,Silva, Regina M.P.,Lima, Nuno E.M.,Raposo, M.Manuela M.
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p. 293 - 300
(2014/01/06)
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- Synthesis and antibacterial evaluation of furan derivatives bearing a rhodanine moiety
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Two series of furan derivatives bearing a rhodanine moiety (4a-l and 5a-l) have been synthesized, characterized, and evaluated for their antibacterial activity. The majority of these compounds showed potent levels of inhibitory activity against a variety of different Gram-positive bacteria, including multidrug-resistant clinical isolates, with minimum inhibitory concentration (MIC) values in the range of 2-16 μg/mL. In particular, compound 4l was found to be the most potent of the synthesized compounds against the multidrug-resistant strains, with a MIC value of 2 or 4 μg/mL. None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64 μg/mL. An examination of the cytotoxicities of these agents revealed that they displayed low levels of toxicity toward HeLa cells. All of the compounds synthesized in the current paper were characterized by 1H and 13C NMR, infrared, and mass spectroscopy. Graphical Abstract: Two novel series of furan derivatives bearing a rhodanine moiety were synthesized, and evaluated for their antibacterial activity. Compounds 4l and 5a presented high potency against several multidrug-resistant clinical isolates.[Figure not available: see fulltext.]
- Che, Jian,Zheng, Chang-Ji,Song, Ming-Xia,Bi, Ya-Jing,Liu, Yi,Li, Yin-Jing,Wu, Yan,Sun, Liang-Peng,Piao, Hu-Ri
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p. 426 - 435
(2014/03/21)
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- An efficient continuous flow approach to furnish furan-based biaryls
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Suzuki cross-couplings of 5-formyl-2-furanylboronic acid with activated or neutral aryl bromides were performed under continuous flow conditions in the presence of (Bu)4N+F- and the immobilised t-butyl based palladium cata
- Trinh, Trieu N.,Hizartzidis, Lacey,Lin, Andrew J. S.,Harman, David G.,McCluskey, Adam,Gordon, Christopher P.
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p. 9562 - 9571
(2015/02/19)
-
- 5-substituted-2-furaldehydes: A synthetic protocol utilizing an organozinc route
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Facile synthetic routes for the preparation of a wide range of 5-substituted 2-furaldehydes have been revealed. They were accomplished through either Pd-catalyzed cross-coupling reaction of various aryl- and heteroarylzinc halides with 5-bromo-2-furaldehyde or utilization of a new organozinc reagent, 5-(1,3-dioxolan-2-yl)-2-furanylzinc bromide, which was easily prepared by the direct insertion of highly active zinc to 2-(5-bromofuran-2-yl-1,3-dioxolane. Of special note is the uniqueness of using a new organozinc reagent, representing a first example of the direct synthesis of the corresponding organozinc halide. The subsequent coupling reactions in various types of reaction conditions led to the formation of somewhat different furan derivatives. It is also of significance that all of the cross-coupling reactions were carried out under mild conditions.
- Kim, Seung-Hoi,Rieke, Reuben D.
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p. 1984 - 1993
(2013/04/10)
-
- Synthesis and biological evaluation of nitromethylene neonicotinoids based on the enhanced conjugation
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The neonicotinoids with a nitroconjugated system had excellent bioactivity, which could rival imidacloprid, and has been previously reported. However, the photodegradation and hydrolysis of this series of neonicotinoids was very quick according to our further investigation, which cannot be developed as a pesticide further. The approach to further enhance the conjugation was tried not only to increase the bioactivities but also to improve the stability in water and in the sun. A substituted phenyl group was introduced into the furan ring of compound 3. A total of 13 novel neonicotinoid analogues with a higher conjugation system were designed and synthesized. The target molecular structures have been confirmed on the basis of satisfactory analytical and spectral data. All compounds presented significant insecticidal activities on cowpea aphid (Aphis craccivora), cotton aphid (Aphis gossypii), and brown planthopper (Nilaparvata lugens). The stability test exhibited that the stability of novel analogues in water and under the mercury lamp has been improved significantly in comparison to compound 3.
- Lu, Siyuan,Zhuang, Yingying,Wu, Ningbo,Feng, Yue,Cheng, Jiagao,Li, Zhong,Chen, Jie,Yuan, Jing,Xu, Xiaoyong
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p. 10858 - 10863
(2014/01/06)
-
- Development of a novel class of B-RafV600E-selective inhibitors through virtual screening and hierarchical hit optimization
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Oncogenic mutations in critical nodes of cellular signaling pathways have been associated with tumorigenesis and progression. The B-Raf protein kinase, a key hub in the canonical MAPK signaling cascade, is mutated in a broad range of human cancers and especially in malignant melanoma. The most prevalent B-RafV600E mutant exhibits elevated kinase activity and results in constitutive activation of the MAPK pathway, thus making it a promising drug target for cancer therapy. Herein, we describe the development of novel B-RafV600E selective inhibitors via multi-step virtual screening and hierarchical hit optimization. Nine hit compounds with low micromolar IC 50 values were identified as B-RafV600E inhibitors through virtual screening. Subsequent scaffold-based analogue searching and medicinal chemistry efforts significantly improved both the inhibitor potency and oncogene selectivity. In particular, compounds 22f and 22q possess nanomolar IC 50 values with selectivity for B-RafV600Ein vitro and exclusive cytotoxicity against B-RafV600E harboring cancer cells.
- Kong, Xiangqian,Qin, Jie,Li, Zeng,Vultur, Adina,Tong, Linjiang,Feng, Enguang,Rajan, Geena,Liu, Shien,Lu, Junyan,Liang, Zhongjie,Zheng, Mingyue,Zhu, Weiliang,Jiang, Hualiang,Herlyn, Meenhard,Liu, Hong,Marmorstein, Ronen,Luo, Cheng
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experimental part
p. 7402 - 7417
(2012/10/08)
-
- Mono- and biscouplings using triarylbismuths for the atom-efficient arylations of functionalized furans under palladium catalysis
-
Palladium-catalyzed cross-coupling reactions of functionalized bromofurans with triarylbismuths have been described for the atom-economic synthesis of functionalized arylfuran systems. The coupling reactions using triarylbismuths with various 2-bromofurans and 2,5-dibromofuran underwent smoothly to afford the corresponding 2-arylfurans and 2,5-diarylfurans in high yields in a short reaction time (one hour). Georg Thieme Verlag Stuttgart · New York.
- Rao, Maddali L. N.,Awasthi, Dheeraj K.,Talode, Jalindar B.
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supporting information; experimental part
p. 1907 - 1912
(2012/09/22)
-
- Singlet oxygen generation by novel NIR BODIPY dyes
-
Five novel near-infrared BODIPY dyes were prepared for improved singlet oxygen generation using thiophene and bromine. Theoretical, optical, photostable, and singlet oxygen generation characteristics of these dyes were assessed. Predicted excitation energ
- Awuah, Samuel G.,Polreis, Jason,Biradar, Vidya,You, Youngjae
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scheme or table
p. 3884 - 3887
(2011/09/21)
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- BROAD SPECTRUM ANTIVIRAL AND ANTIPARASITIC AGENTS
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The invention provides compounds represented by the formulae: (I) and (II) where the compounds are useful in treating, for example, viral and/or parasitic infections. Also provided are pharmaceutical compositions comprising the compounds and methods of treatment using the compounds.
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Page/Page column 42
(2011/11/01)
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- A convenient synthesis of 5-aryl- and 5-heteroaryl-2-furaldehydes by the cross-coupling reaction of organozincs
-
An efficient synthetic route for the preparation of 5-heteroaryl- and 5-aryl-2-furaldehydes has been developed. It has been accomplished by the palladium(0)-catalyzed cross-coupling reaction of heteroarylzinc and arylzinc reagents with 5-bromo-2-furaldehyde under very mild conditions.
- Kim, Seung-Hoi,Rieke, Reuben D.
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experimental part
p. 2657 - 2659
(2010/06/19)
-
- CYCLIC CARBOXYLIC ACID RHODANINE DERIVATIVES FOR THE TREATMENT AND PREVENTION OF TUBERCULOSIS
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Disclosed are methods for the prevention or treatment of tuberculosis in a subject infected with Mycobacterium tuberculosis by administering rhodanine derivatives of formula (I), as well as some novel such compounds. Other embodiments are also disclosed.
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Page/Page column 9
(2010/08/22)
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- FLUORESCENT COMPOUND AND LABELING AGENT COMPRISING THE SAME
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A novel fluorescent compound having a high light fastness, high fluorescence quantum yield and sharp absorption spectrum, which emits fluorescence having a wavelength in long wavelength region, as well as its use as a labeling agent, is disclosed. In Form
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Page/Page column 29-30; 35
(2009/03/07)
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- Bright, color-tunable fluorescent dyes in the Vis/NIR region: Establishment of new "tailor-made" multicolor fluorophores based on borondipyrromethene
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A new series of high-performance fluorophores named Keio Fluors (KFL), which are based on borondipyrromethene (BODIPY), are reported. The KFL dyes cover a wide spectral range from the yellow (547 nm) to the near-infrared (NIR, 738 nm) region, and their emission wavelength could be easily and subtly controlled based on simple molecular modifications only, without losing their optical properties. This "tailor-made" synthetic strategy for tuning the emission wavelength enabled the creation of fourteen KFL dyes with well-controlled emission colors (yellow, orange, red, far-red, and NIR). Moreover, these KFL dyes also retain their excellent optical properties, such as spectral bands sharper than quantum dots, high extinction coefficients (140000-316000 M-1 cm-1), and high quantum yields (0.56-0.98), without any critical solvent polarity dependent decrease of their brightness. These advantageous characteristics make the KFL dyes potentially useful as new candidates of fluorescent standard dyes to substitute or to complement existing long-wavelength fluorescent dyes, such as cyanines, oxazines, rhodamines, or other BODIPY dyes.
- Umezawa, Keitaro,Matsui, Akihiro,Nakamura, Yuki,Citterio, Daniel,Suzuki, Koji
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scheme or table
p. 1096 - 1106
(2009/09/29)
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- C-H and C-Si functionalization of furan derivatives: Palladium-catalyzed homocoupling and arylation reactions
-
Palladium-catalyzed arylation reactions of benzofuran derivatives are shown to take place at the carbon - hydrogen bond or carbon - silicon bond adjacent to the oxygen atom. A variety of furan derivatives are obtained in good yields. Georg Thieme Verlag S
- Matsuda, Shigeru,Takahashi, Masabumi,Monguchi, Daiki,Mori, Atsunori
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scheme or table
p. 1941 - 1944
(2010/04/04)
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- Bright, color-tunable fluorescent dyes in the visible-near-infrared region
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The newly synthesized Keio Fluors, which are based on boron-dipyrromethene (BDP), have excellent and useful optical properties: vivid colors and sharp emission in the visible-near-infrared region (583-738 nm), high quantum yields (Φ: 0.56-0.98), high exti
- Umezawa, Keitaro,Nakamura, Yuki,Makino, Hiroshi,Citterio, Daniel,Suzuki, Koji
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p. 1550 - 1551
(2008/09/17)
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- Non-thiol farnesyltransferase inhibitors: N-(4-tolylacetylamino-3- benzoylphenyl)-3-arylfurylacrylic acid amides
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We have designed arylfurylacryl-substituted benzophenones as non-thiol farnesyltransferase inhibitors utilizing a novel aryl binding site of farnesyltransferase. These compounds display activity in the low nanomolar range. We have designed arylfurylacryl-
- Mitsch, Andreas,Wi?ner, Pia,Silber, Katrin,Haebel, Peter,Sattler, Isabel,Klebe, Gerhard,Schlitzer, Martin
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p. 4585 - 4600
(2007/10/03)
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- Dantrolene analogues revisited: General synthesis and specific functions capable of discriminating two kinds of Ca2+ release from sarcoplasmic reticulum of mouse skeletal muscle
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The general synthesis of dantrolene analogues with various substituents on its phenyl ring has been developed via palladium-catalyzed cross-coupling reactions, the Stille or Suzuki reaction, as the key step. The effects of synthesized analogues have been evaluated by two kinds of Ca2+ release modes from sarcoplasmic reticulum (SR) of mouse skeletal muscle fibers based on: (1) the measurement of twitch contraction caused by the physiological Ca2+ release (PCR) of intact skeletal muscle and (2) the rate of Ca2+-induced Ca2+ release (CICR) in saponin-treated skinned muscle fibers. Although dantrolene, a lead compound, inhibits both twitch contraction and CICR, some structurally modified analogues exhibit one or the other of these effects. The methoxy congener, GIF-0185, potently inhibits the twitch contraction without affecting the CICR, while GIF-0166 and GIF-0248, the ortho-nitro regioisomer and ortho, ortho-dinitro substituted analogues, respectively, doubly potentiate the CICR exclusively.
- Hosoya, Takamitsu,Aoyama, Hiroshi,Ikemoto, Takaaki,Kihara, Yasutaka,Hiramatsu, Toshiyuki,Endo, Makoto,Suzuki, Masaaki
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p. 663 - 673
(2007/10/03)
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- Efficient coupling of heteroaryl halides with arylboronic acids in the presence of a palladium-tetraphosphine catalyst
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Cis, cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl) cyclopentane: ·1/2[PdCl(C3H5)]2 system catalyses the Suzuki cross-coupling of heteroaryl halides with a range of arylboronic acids with very high ratio substrate/catalyst in good yields. Substrates such as pyridines, quinolines, thiophenes, an indole, pyrimidines or a furane have been used successfully.
- Feuerstein, Marie,Doucet, Henri,Santelli, Maurice
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p. 327 - 336
(2007/10/03)
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- Structure-activity relationships of novel anti-malarial agents part 8. Effect of different central aryls in biarylacryloylaminobenzophenones on antimalarial activity
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Replacement of the 2,5-disubstituted furyl residue present in the known antimalarial agents 8 by other aryl residues resulted in a more or less reduced antimalarial activity in most cases. The only exemption was the 2,4-thienylene compound 11a displaying activity with an IC50 value of 120 nM. In conclusion, the 2,5-furylene compound 8e remains to represent the most active antimalarial agent in this series of farnesyltransferase inhibitors.
- Wiesner,Mitsch,Altenkaemper,Ortmann,Jomaa,Schlitzer, Martin
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p. 854 - 856
(2007/10/03)
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- Synthesis of 5-Pyridyl-2-furaldehydes via palladium-catalyzed cross-coupling with triorganozincates
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(Equation Presented) 5-Pyridyl-and 5-aryl-2-furaldehydes are prepared from furaldehyde diethyl acetal in a four-step, one-pot procedure: (i) deprotonation; (2) Li to Zn transmetalation; (3) Pd-mediated cross-coupling; (4) aldehyde deprotection. Triorganozincate 7 was found to transfer all three groups in the Pd-catalyzed cross-coupling reaction with haloaromatics.
- Gauthier Jr., Donald R.,Szumigala Jr., Ronald H.,Dormer, Peter G.,Armstrong III, Joseph D.,Volante,Reider, Paul J.
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p. 375 - 378
(2007/10/03)
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- Structure-activity relationships of novel anti-malarial agents. Part 4: N-(3-Benzoyl-4-tolylacetylaminophenyl)-3-(5-aryl-2-furyl)acrylic acid amides
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In a previous report, we have described novel anti-malarial compounds based on a 2,5-diaminobenzophenone scaffold. Here, we have invesigated acryloyl derivatives carrying a biaryl structure consisting of a terminal aryl residue and a central 2-furyl ring. Several compounds were obtained in the series of para-substituted phenylfurylacryloyl derivatives that displayed improved anti-malarial activity in comparison to earlier described derivatives. From the structure-activity relationships it can be deduced that there has to be a lipophilic moiety in the para-position of the terminal phenyl residue. Furthermore, there are indications that, alternatively, activity may benefit from the presence of a polar moiety with hydrogen bond acceptor properties.
- Wiesner, Jochen,Mitsch, Andreas,Wissner, Pia,Kraemer, Oliver,Jomaa, Hassan,Schlitzer, Martin
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p. 2681 - 2683
(2007/10/03)
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- Efficient coupling of heteroaryl bromides with arylboronic acids in the presence of a palladium-tetraphosphine catalyst
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The cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C 3H5)]2 system catalyses the Suzuki cross-coupling of heteroaryl bromides with arylboronic acids with a very high substrate/catalyst ratio in good yields. Substrates such as pyridines, quinolines, thiophenes, an indole, a pyrimidine or a furane have been used successfully.
- Feuerstein, Marie,Doucet, Henri,Santelli, Maurice
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p. 5659 - 5662
(2007/10/03)
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- A practical one-pot synthesis of 5-aryl-2-furaldehydes
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A useful one-pot synthesis of 5-aryl-2-furaldehydes via palladium-mediated Suzuki coupling of aryl halides with in situ generated 5-(diethoxymethyl)-2-furylboronic acid is described. The procedure has general applicability, delivers high yields, and is amenable to scale-up.
- McClure,Roschangar,Hodson,Millar,Osterhout
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p. 1681 - 1685
(2007/10/03)
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- Regioselective palladium-catalyzed arylation of 2-furaldehyde.
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An efficient regioselective method for the direct arylation of 2-furaldehyde to provide a range of pi-diverse 5-aryl-2-formylfuran derivatives is described. The method employs functionalized aryl halides and a catalytic amount of palladium(II) chloride under relatively mild conditions.
- McClure,Glover,McSorley,Millar,Osterhout,Roschangar
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p. 1677 - 1680
(2007/10/03)
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- PHOTOCHEMICAL ARYLATION OF FURANS AND THIOPHENES
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The photochemical behaviour of furan and thiophene is discussed with special attention to photoarylation of thiophene.The irradiation of 5-bromofuran-2-carbaldehyde, 41, in benzene gave good yields of the corresponding 5-phenyl derivative 42.The reaction 41--->42 has been studied considering the photochemical behaviour changing both the position of the halogen on the furan ring and the effect of the solvent.Kinetic and spectroscopic data are in agreement with the formation of a transient triplet exciplex in this type of reactions.The use of both the iodo derivative 50 and acetonitrile as solvent allowed the conversion to be optimized.On the contrary, the irradiation of 41 in diethyl ether or in an amine furnished the dehalogenation product 53.Photoarylation can be extended to thiophene derivatives and aromatic or heteroaromatic donors.The reaction also occurs with halothiophenes or thiazoles as donors, or by using halothiophene carboesters as acceptors.On the contrary, halothiophene carbonitriles are unreactive under similar conditions.Some applications to the synthesis of naturally occurring polythiophenes are reported.The target compounds were obtained through photoarylation and subsequent reaction with alkynes in the presence of palladium(0) complexes as catalysts.The role of polythiophenes in the environment is discussed.The hypothesis that the bioactivity of these compounds is related to the capability to be singlet-oxygen sensitizers is supported by the finding that all the bithiophenes synthesized are singlet-oxygen sensitizers.
- D'Auria, Maurizio
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p. 419 - 434
(2007/10/02)
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- AN IMPROVED SYNTHETIC METHOD FOR 5-ARYL-2-FURANCARBALDEHYDE
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An improved synthetic method for the preparation of 5-aryl-2-furancarbaldehyde via a photochemical arylation of 5-iodo-2-furancarbaldehyde is described.
- D'Auria, Maurizio,Antonioletti, Roberto,Mico, Antonella De,Piancatelli, Giovanni
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p. 1575 - 1578
(2007/10/02)
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- CATALYTIC ARYLATION OF FURFURAL BY ARENEDIAZONIUM SALTS
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A series of 5-arylfurfurals were obtained by the reaction of furfural with arenediazonium chlorides in the presence of cupric chloride or ferrous chloride.The optimum reaction conditions depend on the nature of the substituent in the aromatic ring of the
- Obushak, N. D.,Lesyuk, A. I.,Ganushchak, N. I.,Mel'nik, G. M.,Zavalii, P. Yu.
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p. 2093 - 2097
(2007/10/02)
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- CERTAIN ANTIHYPERTENSIVE 1-[2-[3-CARBAMOYL-4-HYDROXYPHENOXY]ALKYLENEAMINO]-HETEROCYCLIC PHENOXY-PROPANOL DERIVATIVES
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The invention relates to novel substituted phenyl ethers of the formula STR1 in which Ar represents a mono-or bi-cyclic carbocyclic aryl radical, or a mono-or bi-cyclic heterocyclic aryl radical bonded to a phenylene radical by way of a ring carbon atom,Ph represents a phenylene radical,n has the value 0 to 1 andalk represents alkylene having from 2 to 5 carbon atoms, the nitrogen atom and the oxygen atom or, if n is 0, the aromatic radical being separated from each other by at least two carbon atoms in the unbranched chain, andR 1 and R. sub.2 each represents, independently of the other, hydrogen or lower alkyl, or together represent lower alkylene, oxa-lower alkylene, thia-lower alkylene, aza-lower alkylene or N-lower alkyl-aza-lower alkylene, and salts thereof, especially pharmaceutically acceptable non-toxic acid addition salts. Such compounds possess, on the one hand, blocking properties towards β-adrenergic receptors and can therefore be used as β-receptor-blockers with or without cardioselectivity for the treatment of Angina pectoris, hypertrophic cardiomyopathy and heart rhythm disorders and also as blood-pressure-reducing agents. On the other hand, such compounds possess β-receptor-stimulating properties and can therefore be used as positively inotropically active agents, especially as cardiotonics, for the treatment of heart muscle insufficiency.
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- 5-Phenyl-2-furamidines: A new chemical class of potential antidepressants
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A series of 5-phenyl-2-furamidines has been synthesized and evaluated for antidepressant activities. Substitution in the phenyl ring with a nitro (4) or an amino (12) group in the ortho-position resulted in an increase in antidepressant activity. Both 4 and 12 antagonized tetrabenazine-induced ptosis in rodents and inhibited norepinephrine (noradrenaline) uptake into crude synaptosomes of whole mouse brain at doses or concentrations comparable to those of the tricyclic antidepressants. However, these compounds did not possess the anticholinergic and antihistaminic activities common to tricyclic antidepressants. In addition, they lacked monoamine oxidase inhibitory activity. The 5-phenyl-2-furamidines represent a new chemical class of antidepressants and may be useful for depressive patients who cannot tolerate the compromising side effects of the tricyclic antidepressants and monoamine oxidase inhibitors.
- Pong,Pelosi Jr.,Wessels,Yu,Burns,White,Anthony Jr.,Ellis,Wright,White Jr.
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p. 1411 - 1416
(2007/10/02)
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