Search results for " Disc"
showing 10 items of 9209 documents
Pharmacophore-Based Design of New Chemical Scaffolds as Translational Readthrough-Inducing Drugs (TRIDs)
2020
[Image: see text] Translational readthrough-inducing drugs (TRIDs) rescue the functional full-length protein expression in genetic diseases, such as cystic fibrosis, caused by premature termination codons (PTCs). Small molecules have been developed as TRIDs to trick the ribosomal machinery during recognition of the PTC. Herein we report a computational study to identify new TRID scaffolds. A pharmacophore approach was carried out on compounds that showed readthrough activity. The pharmacophore model applied to screen different libraries containing more than 87000 compounds identified four hit-compounds presenting scaffolds with diversity from the oxadiazole lead. These compounds have been s…
Copper(I)-catalysed regioselective synthesis of pyrazolo[5,1-c]-1,2,4-triazoles: A DFT mechanistic study
2017
Abstract Formation of pyrazolo[5,1-c]-1,2,4-triazoles by means of Cu(I)-catalysed [3+2] cycloaddition (32CA) reactions of C,N-cyclic azomethine imines with phenylacetylene, experimentally reported by Katritzky et al. (JOC 2012, 77, 5813), was studied using the density functional theory (DFT) method. Comparison with the uncatalysed 32CA reaction indicates that the Cu(I) catalyst provides new reaction pathways with lower electronic energy barriers in dichloromethane as solvent. The mechanism proposed by Katritzky for the Cu(I) catalysed reaction is compared with that proposed by Sharpless et al. (JACS 127, 2005, 210). The major difference between these two mechanisms lies in the coordination …
Proline-Modified Porphyrin Catalysts for Enantioselective Epoxidations: Design, Synthesis, and Reactivity
2004
International audience; The syntheses of various strapped and −picket-fence× chiral porphyrins are described, and their reactivities towards the enantioselective epoxidation of alkenes are reported. Four L-proline residues provide the chiralityfor the various meso-substituted catalysts, which differ by either the spatial arrangement of the stereogenic centers or the nature and length of the straps. The resulting bridged structures possess four amide linkages ineach strap, leading to highly rigid molecules with well-defined geometries whereas the strapped Fe catalysts gave rise to only moderate enantioselectivities, the C2-symmetrical ones being superior to the D2-symmetrical compounds. The …
Isomerization of perchlorohexatriene in three consecutive rearrangements to perchloro-2-vinylbutadiene
2017
Perchlorohexatriene isomerizes in three subsequent rearrangements to perchloro-2-vinylbutadiene. A radical-induced Z-E-equilibration of linear perchlorohexatrienes is followed by cyclization to a methylenecyclopentene. Under flash-vacuum pyrolysis conditions, a ring contraction to 1,2-dimethylenecyclobutane occurs. In the condensed phase, a radical-induced ring opening generates the branched perchloro-vinylbutadiene. All compounds are converted to hexachlorobenzene, but only at very high temperatures.
Synthesis and in vitro biological evaluation of novel diaminothiophene scaffolds as antitumor and anti-influenza virus agents. Part 2
2017
On the basis of high-throughput screening, fragment-based drug discovery, structure–activity relationships and building block analysis methods, herein we report the synthesis and biological evaluation of a novel series of diethyl 2,5-diaminothiophene-3,4-dicarboxylate derivatives. All of the prepared Schiff bases (with mono-, di- and poly-substituents at the aromatic portion), mono- and bis-amides of diethyl 2,5-diaminothiophene-3,4-dicarboxylate, were evaluated against various human cancer and non-cancerous (only for active compounds) cell lines, as well as influenza A (subtypes FM/1/47/H1N1, hanfang/359/95/H3N2) and B (subtype jifang/13/97) viruses. The obtained results suggest that some …
Synthesis and structural properties of hexaaza[5]helicene containing two [1,2,3]triazolo[1,5-a]pyridine moieties
2013
Abstract We have synthesized a novel hexaaza[5]helicene in a straightforward way from neocuproine. The crystal structure has been elucidated with direct-space strategy TALP which demonstrates the power of the powder X-ray diffraction technique. In this crystal structure it is possible to see an interplanar angle of 33(1)° between the two triazolopyridine rings. The centrosymmetric crystal structure is a racemic mixture, but the resolution was not possible due to a ring-chain isomerization in a solution that produces a dynamic racemization.
A roadmap for amphibious drilling at the Campi Flegrei caldera: insights from a MagellanPlus workshop
2019
Large calderas are among the Earth's major volcanic features. They are associated with large magma reservoirs and elevated geothermal gradients. Caldera-forming eruptions result from the withdrawal and collapse of the magma chambers and produce large-volume pyroclastic deposits and later-stage deformation related to post-caldera resurgence and volcanism. Unrest episodes are not always followed by an eruption; however, every eruption is preceded by unrest. The Campi Flegrei caldera (CFc), located along the eastern Tyrrhenian coastline in southern Italy, is close to the densely populated area of Naples. It is one of the most dangerous volcanoes on Earth and represents a key example of an acti…
Application of entropic approach to estimate the mean flow velocity and Manning roughness coefficient in a high-curvature flume
2016
The entropy-based approach allows the estimation of the mean flow velocity in open channel flow by using the maximum flow velocity. The linear relationship between the mean velocity, umax, and the mean flow velocity, um, through the dimensionless parameter Φ(M), has been verified both in natural rivers and in laboratory channels. Recently, the authors of this study investigated the reliability of the entropy-based formula in a straight channel and under different bed and side-walls' roughness conditions. The present study aims to further validate the entropy-based approach and to explore the effectiveness of entropy-based formula in high curvature channels. Results show that as the effect o…
Stochastic Galerkin method for cloud simulation
2018
AbstractWe develop a stochastic Galerkin method for a coupled Navier-Stokes-cloud system that models dynamics of warm clouds. Our goal is to explicitly describe the evolution of uncertainties that arise due to unknown input data, such as model parameters and initial or boundary conditions. The developed stochastic Galerkin method combines the space-time approximation obtained by a suitable finite volume method with a spectral-type approximation based on the generalized polynomial chaos expansion in the stochastic space. The resulting numerical scheme yields a second-order accurate approximation in both space and time and exponential convergence in the stochastic space. Our numerical results…
Benchmarking numerical models of brittle thrust wedges
2016
International audience; We report quantitative results from three brittle thrust wedge experiments, comparing numerical resultsdirectly with each other and with corresponding analogue results. We first test whether the participatingcodes reproduce predictions from analytical critical taper theory. Eleven codes pass the stable wedgetest, showing negligible internal deformation and maintaining the initial surface slope upon horizontaltranslation over a frictional interface. Eight codes participated in the unstable wedge test that examinesthe evolution of a wedge by thrust formation from a subcritical state to the critical taper geometry. Thecritical taper is recovered, but the models show two…