- Imaging the static dielectric constant in vitro and in living cells by a bioconjugable GFP chromophore analog
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A fluorescent probe structurally similar to the GFP chromophore is demonstrated to report the local static dielectric constant. This probe can be chemically functionalized for selective targeting at the intracellular level. The Royal Society of Chemistry
- Signore, Giovanni,Abbandonato, Gerardo,Storti, Barbara,Stoeckl, Martin,Subramaniam, Vinod,Bizzarri, Ranieri
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Read Online
- Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)
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Histone Deacetylases (HDACs) are among the most attractive and interesting targets in anticancer drug discovery. The clinical relevance of HDAC inhibitors (HDACIs) is testified by four FDA-approved drugs for cancer treatment. However, one of the main drawbacks of these drugs resides in the lack of selectivity against the different HDAC isoforms, resulting in severe side effects. Thus, the identification of selective HDACIs represents an exciting challenge for medicinal chemists. HDACIs are composed of a cap group, a linker region, and a metal-binding group interacting with the catalytic zinc ion. While the cap group has been extensively investigated, less information is available about the effect of the linker on isoform selectivity. To this aim, in this work, we explored novel linker chemotypes to direct isoform selectivity. A small library of 25 hydroxamic acids with hitherto unexplored linker chemotypes was prepared. In vitro tests demonstrated that, depending on the linker type, some candidates selectively inhibit HDAC1 over HDAC6 isoform or vice versa. Docking calculations were performed to rationalize the effect of the novel linker chemotypes on biologic activity. Moreover, four compounds were able to increase the levels of acetylation of histone H3 or tubulin. These compounds were also assayed in breast cancer MCF7 cells to test their antiproliferative effect. Three compounds showed a significant reduction of cancer proliferation, representing valuable starting points for further optimization.
- Linciano, Pasquale,Benedetti, Rosaria,Pinzi, Luca,Russo, Fabiana,Chianese, Ugo,Sorbi, Claudia,Altucci, Lucia,Rastelli, Giulio,Brasili, Livio,Franchini, Silvia
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- Enantioselective Access to Chiral 2-Substituted 2,3-Dihydrobenzo[1,4]dioxane Derivatives through Rh-Catalyzed Asymmetric Hydrogenation
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Rh-catalyzed asymmetric hydrogenation of various benzo[b][1,4]dioxine derivatives was successfully developed to prepare chiral 2-substituted 2,3-dihydrobenzo[1,4]dioxane derivatives using ZhaoPhos and N-methylation of ZhaoPhos ligands with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess (ee), turnover number (TON) = 24 000). Moreover, this asymmetric hydrogenation methodology, as the key step with up to 10 000 TON, was successfully applied to develop highly efficient synthetic routes for the construction of some important biologically active molecules, such as MKC-242, WB4101, BSF-190555, and (R)-doxazosin·HCl.
- Yin, Xuguang,Huang, Yi,Chen, Ziyi,Hu, Yang,Tao, Lin,Zhao, Qingyang,Dong, Xiu-Qin,Zhang, Xumu
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supporting information
p. 4173 - 4177
(2018/07/29)
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- Halogen bonding enhances activity in a series of dual 5-HT6/D2 ligands designed in a hybrid bioisostere generation/virtual screening protocol
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A novel hybrid bioisostere generation/virtual screening method combined with narrowing of chemical space through similarity to compounds that are active at the second target was successfully applied for the development of structurally new dual 5-HT6/D2 receptor ligands. Consequently, a series of derivatives of the found hit 1d (N-[2-(dimethylamino)ethyl]-N-(2-phenylethyl)aniline) was synthesized. The most active 5-HT6/D2 ligands also showed affinity for 5-HT7R and 5-HT2AR. The para-chloroaniline derivative was identified as a potent dual 5-HT6/5-HT7 receptor antagonist (Ki = 24 nM and Kb = 30 nM, Ki = 4 nM and Kb = 1.4 nM, respectively). In the case of halogen-containing compounds, interesting structure-activity relationships were observed at 5-HT6, D2 and 5-HT7 receptors, and the ligand-receptor complexes were subsequently examined using a molecular modelling approach that combined quantum-polarized ligand docking (QPLD) and Molecular-Mechanics-Generalized-Born/Surface Area (MM/GBSA) free-energy calculation, which permitted the identification of putative halogen binding pockets.
- Staroń, Jakub,Warszycki, Dawid,Kurczab, Rafa?,Sata?a, Grzegorz,Bugno, Ryszard,Hogendorf, Adam,Bojarski, Andrzej J.
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p. 54918 - 54925
(2016/07/06)
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- Containing 1,4-benzodioxane structure of the pyrazoline derivatives and the preparation and use thereof
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The invention relates to pyrazoline derivatives comprising a 1,4-benzodioxan structure. The derivatives are characterized in that the derivatives have a general formula as the following. R1, R3, and R3 in the formula are as the following. The pyrazoline d
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Paragraph 0036-0038
(2016/12/01)
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- Ultrasound-assisted synthesis and biological evaluation of 1,4-benzodioxane-2-carboxyl-amino acids and Peptides
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A series of peptides containing 1,4-benzodioxane nucleus were attempted to synthesize by conventional as well as green techniques like microwave-assisted and sonication, using dicyclohexylcarbodiimide (DCC) as a coupling reagent and triethylamine as a bas
- Malipeddi, Himaja,Gowda, Visruth,Das, Moonjit
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p. 113 - 118
(2019/01/16)
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- Synthesis and antibacterial activity of cinnamaldehyde acylhydrazone with a 1,4-benzodioxan fragment as a novel class of potent ss-Ketoacyl-acyl carrier protein synthase III (FabH) inhibitor
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Fatty acid biosynthesis is essential for bacterial survival. ss-Ketoacyl-acyl carrier protein (ACP) synthase III (FabH), is a particularly attractive antibacterial target, since it is central to the initiation of fatty acid biosynthesis. Three series of 2
- Song, Xiaoda,Yang, Yushun,Zhao, Jing,Chen, Yangjian
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p. 1110 - 1118
(2014/12/11)
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- Chemoenzymatic synthesis of piperoxan, prosympal, dibozane, and doxazosin
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The synthesis of both enantiomers of 1,4-benzodioxan-2-carboxylic acid 1, a key synthetic intermediate for the therapeutic agents piperoxan, prosympal, dibozane, and doxazosin was achieved with good yields and high enantioselectivities via the Arthrobacter sp. lipase catalyzed kinetic resolution of ester (±)-17a. The influence of the co-solvents and the immobilization of the lipase upon kinetic resolution demonstrated that immobilized whole cells, in the presence of n-butanol as a co-solvent, resulted in the optimal resolution of the substrate (ee ~99%, E = 535) at 258 mmol (50 g/L) substrate concentration.
- Rouf, Abdul,Gupta, Pankaj,Aga, Mushtaq A.,Kumar, Brijesh,Chaubey, Asha,Parshad, Rajinder,Taneja, Subhash C.
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supporting information
p. 1615 - 1623
(2013/02/22)
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- Discovery of novel 1,4-benzodioxane containing thiazolidinone derivatives as potential antihepatotoxic agent
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In continuance of our search for newer antihepatotoxic agents some novel thiazolidinone derivatives containing 1,4-benzodioxane ring system were synthesized starting from 2,3-dihydro-1,4-benzodioxane-2-carbohydrazide. The synthesized compounds were evalua
- Khalilullah, Habibullah,Khan, Shamshir,Ahsan, Mohamed Jawed,Ahmed, Bahar
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experimental part
p. 575 - 582
(2012/05/19)
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- Design, modification and 3D QSAR studies of novel 2,3-dihydrobenzo[b][1,4] dioxin-containing 4,5-dihydro-1H-pyrazole derivatives as inhibitors of B-Raf kinase
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Two series of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H-pyrazole derivatives C1-C15 and D1-D15 have been synthesized and evaluated for their B-Raf inhibitory and anti-proliferation activities. Compound C14 ((3-(4-bromophenyl)-5-(2-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2,3- dihydrobenzo[b][1,4]dioxin-6-yl)methanone) showed the most potent biological activity against B-RafV600E (IC50 = 0.11 μM) and WM266.4 human melanoma cell line (GI50 = 0.58 μM), being comparable with the positive control Erlotinib and more potent than our previous best compound, while D10 ((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)(5-(3- fluorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)methanone) performed the best in the D series (IC50 = 1.70 μM; GI50 = 1.45 μM). The docking simulation was performed to analyze the probable binding models and poses and the QSAR model was built for reasonable design of B-Raf inhibitors in future. The introduction of 2,3-dihydrobenzo[b][1,4]dioxin structure reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity.
- Yang, Yu-Shun,Li, Qing-Shan,Sun, Shuai,Zhang, Yan-Bin,Wang, Xiao-Liang,Zhang, Fei,Tang, Jian-Feng,Zhu, Hai-Liang
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p. 6048 - 6058
(2012/11/07)
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- Synthesis and antihepatotoxic activity of 2-(substituted-phenyl)-5-(2,3- dihydro-1,4-benzodioxane-2-yl)-1,3,4-oxadiazole derivatives
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Novel 1,3,4-oxadizole derivatives containing the 1,4-dioxane ring system were synthesised starting from 2,3-dihydro-1,4-benzodioxane-2-carbohydrazide. The synthesised compounds were evaluated for antihepatotoxic activity against CCl4-induced hepatotoxicity in rats. Some compounds demonstrated a significant antihepatotoxic activity comparable to the standard drug Silymarin.
- Ahmed, Bahar,Habibullah,Khan, Shamshir
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experimental part
p. 216 - 221
(2011/10/18)
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- Process for the preparation of ethyl 2,3-dihydrobenzo[1,4]dioxin-2-carboxylate
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The present invention relates to an improved process for the preparation of ethyl 2,3-dihydrobenzo[1,4]dioxin-2-carboxylate. More particularly the present invention provides a process for the preparation of ethyl 2,3-dihydrobenzo[1,4]dioxin-2-carboxylate in hydrocarbon solvent in the presence of a base and catalytic amount of a phase transfer catalyst.
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- Practical chemical and enzymatic technologies for (S)-1,4-benzodioxan-2-carboxypiperizine intermediate in the synthesis of (S)-doxazosin mesylate
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(S)-1,4-Benzodioxan-2-carboxypiperazine (S)-2, the key chiral intermediate for the synthesis of (S)-doxazosin, was prepared utilizing two approaches: (i) enzymatic resolution of ethyl 1,4-benzodioxan-2-carboxylate with an esterase (Serratia) followed by amide formation; (ii) direct resolution of 1,4-benzodioxan-2-carboxypiperazine 2 with D-tartaric acid. An efficient process for the conversion of (S)-2 to (S)-doxazosin mesylate was developed (80% yield, 99.9% e.e.).
- Fang,Grover, Paul,Han, Zhengxu,McConville, Fran X.,Rossi, Richard F.,Olsson, Damase J.,Kessler, Donald W.,Wald, Stephen A.,Senanayake, Chris H.
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p. 2169 - 2174
(2007/10/03)
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- Substituted heterocyclic compounds, method for preparing and compositions containing same
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The invention relates to compounds of formula (I): wherein: R1, R2and R3are as defined in the description, X is as defined in the description, Y represents an oxygen atom, a sulphur atom, a C(H)qgroup, SO or SO2, n is equal to from 0 to 5, A represents a NR5R6group, and medicinal products containing the same which are useful in treating or in preventing melatoninergic disorders.
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- Studies in the cycloproparene series: 3,8-dioxa-1H-cyclopropa[b]anthracene
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The application of known methodology has provided 2,3-dimethylidene-2,3-dihydro-1,4-benzodioxin (12) as the essential precursor for preparation of the cyclopropa-fused dibenzodioxin 3,8-dioxa-1H-cyclopropa[b]anthracene (14). Cycloproparene (14) is both unstable and acid-sensitive, and readily dimerizes to a mixture of the dihydrotetraoxaheptacene (15) and its heptaphene analogue (16).
- Cooney, Mark J.,Halton, Brian
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p. 533 - 538
(2007/10/03)
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