- Development of a C2-Symmetric Chiral aza Spirocyclic Diol
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A C2-symmetric chiral spirocyclic diol aza-SPINOL containing a spirooxindole scaffold has been designed, synthesized, and optically resolved. The product could be synthesized on gram scale in an overall yield of 22%. Moreover, elaborations of aza-SPINOL to other chiral ligands as well as the preliminary investigation of the related bisphosphine ligand in the desymmetrization of bisallylic amide were reported.
- Guo, Weicong,Liu, Qinzhe,Jiang, Jijun,Wang, Jun
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Read Online
- Small Molecule Control of Morpholino Antisense Oligonucleotide Function through Staudinger Reduction
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Conditionally activated, caged morpholino antisense agents (cMOs) are tools that enable the temporal and spatial investigation of gene expression, regulation, and function during embryonic development. Cyclic MOs are conformationally gated oligonucleotide analogs that do not block gene expression until they are linearized through the application of an external trigger, such as light or enzyme activity. Here, we describe the first examples of small molecule-responsive cMOs, which undergo rapid and efficient decaging via a Staudinger reduction. This is enabled by a highly flexible linker design that offers opportunities for the installation of chemically activated, self-immolative motifs. We synthesized cyclic cMOs against two distinct, developmentally relevant genes and demonstrated phosphine-triggered knockdown of gene expression in zebrafish embryos. This represents the first report of a small molecule-triggered antisense agent for gene knockdown, adding another bioorthogonal entry to the growing arsenal of gene knockdown tools.
- Chen, James K.,Darrah, Kristie,Deiters, Alexander,Lukasak, Bradley,Tsang, Michael,Wesalo, Joshua
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supporting information
p. 18665 - 18671
(2021/11/16)
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- Cu-Catalyzed Chemoselective Reduction of N-Heteroaromatics with NH3·BH3 in Aqueous Solution
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An efficient catalytic system was successfully developed on reduction of N-heteroaromatics with H3N?BH3 as hydrogen source in CuSO4 solution, featuring excellent chemoselectivity as well as very broad functional group tolerance. Various challenging substrates, such as OH-, NH2-, Cl-, Br-, etc., contained quinolines, quinoxalines, 1,5-naphthyridines and quinazolines were all reduced smoothly. Mechanistic studies suggested that [Cu-H] intermediate might be generated from NH3?BH3, which was believed to form with H3N?BH3 in CuSO4 solution.
- Gao, Chao,Xuan, Qingqing,Song, Qiuling
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supporting information
p. 2504 - 2508
(2021/07/31)
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- NEAR-INFRARED NERVE-SPARING FLUOROPHORES
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Provided are far red to near-infrared nerve-sparing fluorescent compounds, compositions comprising them, and methods of their use in medical procedures.
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Page/Page column 60-61
(2020/02/17)
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- NERVE-SPECIFIC FLUOROPHORE FORMULATIONS FOR DIRECT AND SYSTEMIC ADMINISTRATION
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Nerve-specific fluorophore formulations for direct or systemic administration are described. The formulations can be used in fluorescence-guided surgery (FGS) to aid in nerve preservation during surgical interventions.
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Paragraph 0209-0210
(2020/03/02)
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- 532nm excited rhodamine fluorescent dye and preparation method thereof
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The invention provides 532nm excited rhodamine fluorescent dye and a preparation method thereof. The structure of the 532nm excited rhodamine fluorescent dye is shown as (1), and the fluorescence quantum yield is higher and reaches 0.85 or above in ethanol through modification with different six-membered ring positions at the nitrogen end. Meanwhile, the raw materials used in the invention are cheap and easily available, the synthesis operation is simple, the requirements on experimental conditions are low, and the dye can be widely applied to the field of bioluminescence imaging.
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Paragraph 0055; 0057-0060
(2020/07/15)
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- Sulfonated 4,7-dichlororhodamine dyes and their application
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The invention describes the preparation and use of sulfonated 4,7-dichlororhodamine dyes having the structure: Wherein R1, R4, R5 and R8 are independently hydrogen, —SO3Y where Y is H or a counterion,
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Page/Page column 11-12
(2020/01/12)
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- Ring-restricted N-nitrosated rhodamine as a green-light triggered, orange-emission calibrated and fast-releasing nitric oxide donor
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Nitric oxide (NO) donors are versatile tools for nitric oxide biology. The biological response of NO is dependent on the transient concentration and the sustained duration. N-Nitrosated rhodamines are photo-triggered and photo-calibrated NO donors. We recently discovered that suppression of the dihedral angle between the N-nitroso fragment with the rhodamine scaffold facilitates NO release. Inspired by this discovery, we developed a fast-releasing NO donor (NOD575) suitable for biological applications, e.g., the pulmonary arterial smooth muscle cells (PASMCs).
- He, Haihong,He, Tingting,Zhang, Ziqian,Xu, Xiu,Yang, Huibin,Qian, Xuhong,Yang, Youjun
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supporting information
p. 1497 - 1499
(2018/09/17)
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- Fluorescent probe containing flavone-based drug active molecule, preparation method and applications thereof
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The invention relates to the field of fluorescent probes, and discloses a fluorescent probe containing a flavone-based drug active molecule, a preparation method and applications thereof, wherein thefluorescent probe is represented by a general formula X-
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Paragraph 0078; 0080-0081
(2018/11/04)
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- Design, synthesis and characterization of potent microtubule inhibitors with dual anti-proliferative and anti-angiogenic activities
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Microtubule has been an important target for anticancer drug development. Here we report the discovery and characterization of a series of fused 4-aryl-4H-chromene-based derivatives as highly potent microtubule inhibitors. Among a total of 37 derivatives synthesized, 23 exhibited strong in vitro anti-proliferative activities against A375 human melanoma cells. The relationship between the biological activities of these microtubule inhibitors and their chemical structure variations was analyzed. Studies of compounds 27a, 19a and 9a in parallel with colchicine as the positive control compound in a panel of biological assays revealed that these compounds blocked cell cycle progression, increased apoptosis, and inhibited HUVEC capillary tube formation at low nanomolar concentrations. The most potent compound 27a was also tested in eight additional cancer cell lines besides A375 cells and two non-cancer cells and showed potent and selective activity on these cancer cells. To understand the molecular and structure mechanism of action of these compounds, tubulin polymerization and molecular docking studies were carried out for 27a as the representative. The results were consistent with the mechanism by which 27a interacts with the colchicine binding site on tubulin and disrupts tubulin polymerization. With potent dual actions of microtubule destabilization and vascular disruption described above, this small molecule can serve as a valuable research probe of the function and role of microtubules in human diseases and promising lead for developing new therapeutic agents.
- Zhang, Huijun,Fang, Xiong,Meng, Qian,Mao, Yujia,Xu, Yan,Fan, Tingting,An, Jing,Huang, Ziwei
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supporting information
p. 380 - 396
(2018/08/17)
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- Regioselective and Chemoselective Reduction of Naphthols Using Hydrosilane in Methanol: Synthesis of the 5,6,7,8-Tetrahydronaphthol Core
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A regioselective and chemoselective method for catalytic synthesis of biologically interesting 5,6,7,8-tetrahydronaphthols by reduction of naphthols was described. The side aromatic hydrocarbons in naphthols were site-selectively reduced, using hydrosilanes in methanol, allowing for retaining functional phenol scaffolds intact. It presents a rare example of using low-cost and air-stable hydrosilane for catalytic reduction of unactivated aromatic hydrocarbons under mild conditions. This reaction is scalable and proceeds in high selectivity without the formation of 1,2,3,4-tetrahydronaphthol byproducts with toleration of sensitive functionalities such as bromide, chloride, fluoride, ketone, ester, and amide.
- He, Yuan,Tang, Jinghua,Luo, Meiming,Zeng, Xiaoming
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supporting information
p. 4159 - 4163
(2018/07/29)
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- Selective hydrogenation of quinolines into 1,2,3,4-tetrahydroquinolines over a nitrogen-doped carbon-supported Pd catalyst
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In this study, we have developed a sustainable method for the hydrogenation of quinolines to 1,2,3,4-tetrahydroquinolines under mild conditions over a nitrogen-doped carbon-supported Pd catalyst with abundant porous structures (abbreviated as Pd/CN). The mesoporous structure of the nitrogen-doped carbon support was prepared by the pyrolysis of glucose and melamine using eutectic salts of KCl and ZnCl2 as the porogen. Due to the high nitrogen content in the support, Pd nanoparticles were homogeneously dispersed on the surface of nitrogen-doped carbon materials with an ultra-small size of 1.9 nm in a narrow size distribution. The as-prepared Pd/CN catalyst showed high catalytic activity towards the hydrogenation of quinolines at 50 °C and 20 bar H2, affording the corresponding 1,2,3,4-tetrahydroquinolines with yields in the range of 86.6-97.8%. More importantly, the Pd/CN catalyst was highly stable without the loss of its catalytic activity during the recycling experiments. The use of renewable resources to prepare the catalyst makes this method promising for the sustainable 1,2,3,4-tetrahydroquinolines from the hydrogenation of quinolines.
- Ren, Yongshen,Wang, Yanxin,Li, Xun,Zhang, Zehui,Chi, Quan
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p. 16694 - 16702
(2018/10/23)
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- A common diaryl ether intermediate for the gram-scale synthesis of oxazine and xanthene fluorophores
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Common ground: Copper-catalyzed coupling reactions can be used for the high-yielding preparation of widely used oxazine and xanthene fluorophores from a common diaryl ether intermediate on a gram-scale (see scheme). This general approach may facilitate th
- Anzalone, Andrew V.,Wang, Tracy Y.,Chen, Zhixing,Cornish, Virginia W.
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supporting information
p. 650 - 654
(2013/02/23)
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- Rhodamine F: A novel class of fluorous ponytailed dyes for bioconjugation
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Incorporation of fluorous ponytails such as polyfluorinated alkyl residues (CH2)m(CF2)nCF3 leads to a novel class of bright rhodamine-based fluorescence dyes. These dyes combine the excellent photophysical properties of the frequently used rhodamine dyes with the unique features of "light" fluorous molecules. One of those features is the possibility to separate substances utilizing fluorous solid-phase extraction (F-SPE), which is based on the specific intermolecular interaction between fluorous compounds. Thus, molecules, which are labeled with these new dyes, are not only accessible to fluorescence experiments, but can also be easily purified (via so-called FluoroFlash columns) prior to use. The dyes were bound to a cell penetrating peptoid (polycationic oligo(N-substituted) glycine) on solid supports. These conjugates were purified with F-SPE before their photophysical and biological properties were investigated. The Royal Society of Chemistry 2013.
- K?lmel, Dominik K.,Rudat, Birgit,Braun, Delia M.,Bednarek, Christin,Schepers, Ute,Br?se, Stefan
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supporting information
p. 3954 - 3962
(2013/07/05)
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- Synthesis of near-IR fluorescent oxazine dyes with esterase-labile sulfonate esters
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Near-IR oxazine dyes are reported that contain sulfonate esters which are rapidly cleaved by esterase activity to unmask highly polar anionic sulfonates. Strategies for the synthesis of these dyes included the development of milder dye condensation conditions with improved functional compatibility and the use of an alkyl halide that allows for the introduction of esterase-labile sulfonates without the need for sulfonation of the target molecule.
- Pauff, Steven M.,Miller, Stephen C.
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supporting information; experimental part
p. 6196 - 6199
(2012/01/06)
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- ACTIVATIBLE DYES
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Novel, activatable dyes, such as photoactivatable dyes, e.g., oxazine dyes, are described. Some of the dyes are targeting dyes that can, e.g., target biomolecules, such as polypeptides, proteins, or nucleic acids. Upon activation, such as by irradiation, the novel dyes rapidly turn on their fluorescence and emit light, such as near-IR light with spatial and temporal precision.
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Page/Page column 13/24
(2009/04/25)
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- Spectrofluorimetric determination of trace nitrite with a novel fluorescent probe
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A simple, sensitive and selective fluorimetric determination for trace nitrites was developed using an unsymmetrical rhodamine with a high fluorescence quantum yield and large Stokes shift. The method is based on the reaction of the unsymmetrical rhodamine with nitrite in an acidic medium to form a nitroso product, which has much lower fluorescence because the electron-withdrawing effect of the nitroso group influences the system of p-π conjugation between N atom and benzene ring. Under optimum conditions, the fluorescence quenching intensity is linear over a nitrite concentration range of 1.0 × 10-8 to 3.5 × 10-7 M. The detection limit is 2.0 × 10-10 M (S/N = 3). The method was applied to the determination of nitrite in tap water and lake water with satisfactory results. The mechanism for the reaction is also reported.
- Liu, Qing-Hao,Yan, Xi-Long,Guo, Jin-Chun,Wang, Dong-Hua,Li, Lei,Yan, Fan-Yong,Chen, Li-Gong
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scheme or table
p. 789 - 793
(2009/12/01)
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- Photostable, amino reactive and water-soluble fluorescent labels based on sulfonated rhodamine with a rigidized xanthene fragment
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Highly water soluble fluorescent dyes were synthesized and transformed into new amino reactive fluorescent labels for biological microscopy. To this end, rhodamine 8 (prepared from 7-hydroxy-1,2,3,4-tetrahydroquinoline (7) and phthalic anhydride in 85% aq. H3PO4) was sulfonated with 30% SO3 in H2SO4 and afforded the water soluble disulfonic acid 3 a (64%). Amidation of the carboxy group in 3 a with 2-(methylamino)ethanol in the presence of O-(7-azabenzotriazol-1-yl)-N,N,N, N′-tetramethyluronium·PF6- (HATU) led to alcohol 3b (66%), which was transformed into the amino reactive mixed carbonate 3d with di(N-succinimidyl)carbonate and Et3N, Reaction of the carboxy group in 3a with MeNH(CH2)2CO2Me and N,N,N′,N′-tetramethyl-O-(N-succinimidyl)-uronium-BF4 - (TSTU) yielded methyl ester 13. After saponification of the aliphatic carboxy group in 13, the compound was converted into NHS-ester 3e (using HATU and Et3N). Heating of 7 with trimellitic anhydride in H3PO4 gave a mixture of dicarboxylic acids 14 and 15 (1:1). Regioisomer 15 was isolated, sulfonated with 30% SO3 in H 2SO4, and disulfonic acid 3f was used for the synthesis of the mono NHS-ester 3g, in which the sterically unhindered carboxy group was selectively activated (with n-hydroxysuccinimide, HATU, and Et3N). The sulfonated rhodamines 3 b, c and f are soluble in water (up to 0.1 M), have excellent photostabilities and large fluorescence quantum yields. Subdiffraction resolution images of tubulin filaments of mammalian cells stained with these dyes illustrate their applicability as labels for stimulated emission depletion microscopy and other fluorescence techniques.
- Boyarskiy, Vadim P.,Belov, Vladimir N.,Medda, Rebecca,Hein, Birka,Bossi, Mariano,Hell, Stefan W.
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supporting information; experimental part
p. 1784 - 1792
(2009/04/07)
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- Synthesis and SAR of novel histamine H3 receptor antagonists
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The synthesis and biological evaluation of novel tetrahydroisoquinoline, tetrahydroquinoline, and tetrahydroazepine antagonists of the human and rat H3 receptors are described. The substitution around these rings as well as the nature of the substituent on nitrogen is explored. Several compounds with high affinity and selectivity for the human and rat H3 receptors are reported.
- Jesudason, Cynthia D.,Beavers, Lisa S.,Cramer, Jeffrey W.,Dill, Joelle,Finley, Don R.,Lindsley, Craig W.,Stevens, F. Craig,Gadski, Robert A.,Oldham, Samuel W.,Pickard, R. Todd,Siedem, Christopher S.,Sindelar, Dana K.,Singh, Ajay,Watson, Brian M.,Hipskind, Philip A.
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p. 3415 - 3418
(2007/10/03)
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- Nonsteroidal androgen receptor agonists based on 4-(trifluoromethyl)- 2H-pyrano[3,2-g]quinolin-2-one
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A series of 2H-pyrano[3,2-g]quinolin-2-ones was prepared and tested for the ability to modulate the transcriptional activity of the human androgen receptor (hAR). The parent compound, 4-(trifluoromethyl)-2H-pyrano[3,2- g]quinolin-2-one, displayed moderate
- Edwards, James P.,Higuchi, Robert I.,Winn, David T.,Pooley, Charlotte L. F.,Caferro, Thomas R.,Hamann, Lawrence G.,Zhi, Lin,Marschke, Keith B.,Goldman, Mark E.,Jones, Todd K.
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p. 1003 - 1008
(2007/10/03)
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- STEROID RECEPTOR MODULATOR COMPOUNDS AND METHODS
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Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
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- Steroid receptor modulator compounds and methods
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Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
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- STEROID RECEPTOR MODULATOR COMPOUNDS AND METHODS
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Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
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- STEROID RECEPTOR MODULATOR COMPOUNDS AND METHODS
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Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
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- STEROID RECEPTOR MODULATOR COMPOUNDS AND METHODS
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Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
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- Steroid receptor modulator compounds and methods
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Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiting steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
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- Tricyclic steroid receptor modulator compounds and methods
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Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
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- Method for preparation of 7-hydroxy-1,2,3,4-tetrahydroquinoline from 1,2,3,4-tetrahydroquinoline
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Methods for the efficient preparation of 7-hydroxy-1,2,3,4-tetrahydroquinoline include a first method in which the acylation of m-aminophenol obtains a lactam which is reduced to give the desired quinoline and a second method in which tetrahydroquinoline is nitrated and hydrogenated and then hydrolyzed to obtain the desire quinoline. 7-hydroxy-1,2,3,4-tetrahydroquinoline is used in the efficient synthesis of four lasing dyes of the rhodamine class.
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- HYDROXYLATION OF INDOLINES AND INDOLES BY HYDROGEN PEROXIDE IN SUPERACIDS
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In SbF5-HF, indolines and indoles are hydroxylated on the aromatic ring, protonated hydrogen peroxide H3O2+ reacting on the protonated substrates.
- Berrier, Christian,Jacquesy, Jean-Claude,Jouannetaud, Marie-Paule,Renoux, Alain
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p. 4565 - 4568
(2007/10/02)
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