1711-02-0Relevant articles and documents
β-sheet-like hydrogen bonds interlock the helical turns of a photoswitchable foldamer to enhance the binding and release of chloride
Lee, Semin,Hua, Yuran,Flood, Amar H.
, p. 8383 - 8396 (2014)
Inspired by halorhodopsins use of photoisomerization to regulate chloride, aryltriazole-based foldamers have been created to "catch and release" chloride ions upon light irradiation of end-appended azobenzenes. The proposed mode of stabilization exploits a β-sheet-like hydrogen-bonding array to cooperatively interlock the ends of a foldamer together with its helical core. We find that the hydrogen-bonding array has a greater influence on stabilizing the helix than the π-stacked seam under the conditions examined (50:50 MeCN/THF). Thus, we show how it is possible to enhance the difference between Cl- binding and release using light-dependent control over the foldamers degree of helix stabilization. Making and breaking three π-π contacts with light caused an 8-fold change in chloride affinity (40 300 M-1 ? 5000 M-1), five π-π contacts produced a 17-fold change (126 000 M-1 ? 7400 M-1), and strategically located hydrogen-bonding units enabled a greater 84-fold differential (970 000 M-1 ? 11 600 M-1). The improved performances were attributed to stepwise increases in the preorganization of the binding pocket that catches chloride while leaving the cis states with just one π-π contact relatively unchanged.
Facile synthesis of para-[18F]fluorohippurate via iodonium ylide-mediated radiofluorination for PET renography
Nkepang, Gregory N.,Hedrick, Andria F.,Awasthi, Vibhudutta,Gali, Hariprasad
, p. 479 - 483 (2016)
para-[18F]fluorohippurate ([18F]PFH) is a renal tubular agent suitable for conducting positron emission tomography (PET) renography. [18F]PFH is currently synthesized by a four-step two-pot procedure utilizing a classical
Benzoylsalicylic acid derivatives as defense activators in tobacco and Arabidopsis
Kamatham, Samuel,Pallu, Reddanna,Pasupulati, Anil Kumar,Singh, Surya Satyanarayana,Gudipalli, Padmaja
, p. 160 - 169 (2017)
Systemic acquired resistance (SAR) is a long lasting inducible whole plant immunity often induced by either pathogens or chemical elicitors. Salicylic acid (SA) is a known SAR signal against a broad spectrum of pathogens in plants. In a recent study, we have reported that benzoylsalicylic acid (BzSA) is a SAR inducer in tobacco and Arabidopsis plants. Here, we have synthesized BzSA derivatives using SA and benzoyl chlorides of various moieties as substrates. The chemical structures of BzSA derivatives were elucidated using Infrared spectroscopy (IR), Nuclear magnetic spectroscopy (NMR) and High-resolution mass spectrometer (HRMS) analysis. The bioefficacy of BzSA derivatives in inducing defense response against tobacco mosaic virus (TMV) was investigated in tobacco and SA abolished transgenic NahG Arabidopsis plants. Interestingly, pre-treatment of local leaves of tobacco with BzSA derivatives enhanced the expression of SAR genes such as NPR1 [Non-expressor of pathogenesis-related (PR) genes 1], PR and other defense marker genes (HSR203, SIPK, WIPK) in systemic leaves. Pre-treatment of BzSA derivatives reduced the spread of TMV infection to uninfected areas by restricting lesion number and diameter both in local and systemic leaves of tobacco in a dose-dependent manner. Furthermore, pre-treatment of BzSA derivatives in local leaves of SA deficient Arabidopsis NahG plants induced SAR through AtPR1 and AtPR5 gene expression and reduced leaf necrosis and curling symptoms in systemic leaves as compared to BzSA. These results suggest that BzSA derivatives are potent SAR inducers against TMV in tobacco and Arabidopsis.
Unifying the Aminohexopyranose- and Peptidyl-Nucleoside Antibiotics: Implications for Antibiotic Design
Barrows, Louis R.,Eiler, Daniel,Kanna Reddy, Hariprasada Reddy,Koch, Michael,Looper, Ryan E.,Sebahar, Paul R.,Serrano, Catherine M.,Testa, Charles A.,Tresco, Ben I. C.,VanderLinden, Ryan T.
, p. 11330 - 11333 (2020)
In search of new anti-tuberculars compatible with anti-retroviral therapy we re-identified amicetin as a lead compound. Amicetin's binding to the 70S ribosomal subunit of Thermus thermophilus (Tth) has been unambiguously determined by crystallography and
Supramolecular bidentate phosphine ligand scaffolds from deconstructed Hamilton receptors
Seidenkranz, Daniel T.,McGrath, Jacqueline M.,Zakharov, Lev N.,Pluth, Michael D.
, p. 561 - 564 (2017)
There is constant demand for new ligand archictectures on which inorganic and organometallic structures can be leveraged. An important, but often synthetically challenging, class of ligands is bidentate phosphines. Here we report self-assembling, supramolecular bidentate ligand scaffolds based on deconstructed Hamilton receptors with binding affinities up to 800 ± 100 M-1
Chemical Proteomics and Phenotypic Profiling Identifies the Aryl Hydrocarbon Receptor as a Molecular Target of the Utrophin Modulator Ezutromid
Wilkinson, Isabel V. L.,Perkins, Kelly J.,Dugdale, Hannah,Moir, Lee,Vuorinen, Aini,Chatzopoulou, Maria,Squire, Sarah E.,Monecke, Sebastian,Lomow, Alexander,Geese, Marcus,Charles, Philip D.,Burch, Peter,Tinsley, Jonathan M.,Wynne, Graham M.,Davies, Stephen G.,Wilson, Francis X.,Rastinejad, Fraydoon,Mohammed, Shabaz,Davies, Kay E.,Russell, Angela J.
, p. 2420 - 2428 (2020)
Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first-in-class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent KD of 50 nm and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies.
Immobilization of (l)-valine and (l)-valinol on SBA-15 nanoporous silica and their application as chiral heterogeneous ligands in the Cu-catalyzed asymmetric allylic oxidation of alkenes
Ashouri, Akram,Mahramasrar, Mahsa,Majidian, Shiva,Rashid, Hersh I,Samadi, Saadi
supporting information, p. 17630 - 17641 (2021/10/04)
SBA-15 nanoporous silica was synthesized by hydrothermal method using P123 surfactant and tetraethoxyortosilicate in acidic condition and then functionalized by 3-chloropropyltrimethoxysilane. Next, by immobilization of chiral amino acid (S)-2-amino-3-methyl butanoic acid (l-valine) and chiral amino alcohol (S)-2-amino-3-methylbutane-1-ol (l-valinol), preparedviathe reduction ofl-valine by NaBH4/I2in THF, on functionalized-SBA-15, chiral heterogeneous ligands AL*-i-Pr-SBA-15 and AA*-i-Pr-SBA-15 were prepared and characterized by FT-IR, XRD, TGA, EDX, SEM, BET-BJH techniques. The asymmetric allylic oxidation of alkenes was done using copper-complexes of these ligands and the as-synthesized peresters. The reactions were optimized by varying various parameters such as temperature, solvent, amount of chiral heterogeneous ligand, as well as the type and amount of copper salt. Under optimized conditions, 6 mg of AL*-i-Pr-SBA-15 and 3.2 mol% of Cu(CH3CN)4PF6in acetonitrile at 50 °C, the chiral allylic ester was obtained with 80% yield and 39% enantiomeric excess in 24 h. The recyclability of the chiral heterogeneous catalysts was also evaluated without significant reduction in the reaction results up to three runs.
Synthesis of new alkenyl iodobenzoate derivatives via Kharasch-Sosnovsky reaction using tert-butyl iodo benzoperoxoate and copper (I) iodide
Samadi, Saadi,Ashouri, Akram,Majidian, Shiva,I Rashid, Hersh
, (2020/11/05)
Abstract: The synthesis of new alkenyl iodobenzoate derivatives as allylic esters was investigated via the reaction of tert-butyl iodobenzoperoxoate with alkenes in the presence of copper salts. The best result was obtained using tert-butyl-iodobenzoperoxoate in the presence of copper (I) iodide (5?mol%) in refluxing acetonitrile with good yield (92%) in 32?h. The structure of peresters and alkenyl iodobenzoate derivatives were characterized on the basis of their FT-IR, 1HNMR, 13CNMR, and Mass spectra. Graphic abstract: The preparation of new iodo-allylic esters from alkenes in the presence of copper salts in good to excellent yields is reported in this article.[Figure not available: see fulltext.]
Using in vitro lipolysis and SPECT/CT in vivo imaging to understand oral absorption of fenofibrate from lipid-based drug delivery systems
Tran, Thuy,B?nl?kke, Peter,Rodríguez-Rodríguez, Cristina,Nosrati, Zeynab,Esquinas, Pedro Luis,Borkar, Nrupa,Plum, Jakob,Strindberg, Sophie,Karagiozov, Stoyan,Rades, Thomas,Müllertz, Anette,Saatchi, Katayoun,H?feli, Urs O.
, p. 375 - 384 (2019/12/25)
Using lipid-based drug delivery systems (LbDDS) is an efficient strategy to enhance the low oral bioavailability of poorly water-soluble drugs. Here the oral absorption of fenofibrate (FF) from LbDDS in rats was investigated in pharmacokinetic, in vitro l
Electrochemical intramolecular C-H/N-H functionalization for the synthesis of isoxazolidine-fused isoquinolin-1(2: H)-ones
Zhang, Lin-Bao,Geng, Rui-Sen,Wang, Zi-Chen,Ren, Guang-Yi,Wen, Li-Rong,Li, Ming
supporting information, p. 16 - 21 (2020/01/13)
A general and practical protocol for the construction of isoxazolidine-fused isoquinolin-1(2H)-ones has been described by electrochemical-oxidation-induced intramolecular annulation via amidyl radicals. In an undivided cell, isoquinolinones could be easily generated from various available amides bearing CONHOR groups under metal-free, additive-free and external oxidant-free conditions. Moreover, this transformation proceeded smoothly by using cheap 95% ethanol as the green solvent and could be extended to the gram scale.
