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
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
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.
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.]
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.
