Synthesis, in vitro, and in vivo biological evaluation and molecular docking simulations of chiral alcohol and ether derivatives of the 1,5-diarylpyrrole scaffold as novel anti-inflammatory and analgesic agents.

Following our previous research on anti-inflammatory drugs (NSAIDs), we report here the synthesis of chiral 1,5-diarylpyrroles derivatives that were characterized for their in vitro inhibitory effects toward cyclooxygenase (COX) isozymes. Analysis of enzymatic affinity and COX-2 selectivity led us to the selection of one compound (+/-)-10b that was further tested in vitro in the human whole blood (HWB) and in vivo for its anti-inflammatory activity in mice. The affinity data have been rationalized through docking simulations

Production of the h_c and h_b and Implications for Quarkonium Spectroscopy

The recent observation of the h_c is an important test of QCD calculations and provides constraints on models of quarkonium spectroscopy. In this contribution I discuss some of these implications and describe methods to search for the h_c and h_b via radiative transitions and other means.Comment: Talk presented at the 1st Meeting of the APS Topical Group on Hadronic Physics (Fermilab, Oct 24-26, 2004), 4 pages, 1 figure, uses jpconf. References adde

Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/cyclooxygenase-1 selectivity.

he important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3- acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain

Minimal Obstructions for Partial Representations of Interval Graphs

Interval graphs are intersection graphs of closed intervals. A generalization of recognition called partial representation extension was introduced recently. The input gives an interval graph with a partial representation specifying some pre-drawn intervals. We ask whether the remaining intervals can be added to create an extending representation. Two linear-time algorithms are known for solving this problem. In this paper, we characterize the minimal obstructions which make partial representations non-extendible. This generalizes Lekkerkerker and Boland's characterization of the minimal forbidden induced subgraphs of interval graphs. Each minimal obstruction consists of a forbidden induced subgraph together with at most four pre-drawn intervals. A Helly-type result follows: A partial representation is extendible if and only if every quadruple of pre-drawn intervals is extendible by itself. Our characterization leads to a linear-time certifying algorithm for partial representation extension

The gluonic condensate from the hyperfine splitting Mcog(χcJ)−M(hc)M_{\rm cog}(\chi_{cJ})-M(h_c) in charmonium

The precision measurement of the hyperfine splitting $\Delta_{\rm HF} (1P, c\bar c)=M_{\rm cog} (\chi_{cJ}) - M(h_c) = -0.5 \pm 0.4$ MeV in the Fermilab--E835 experiment allows to determine the gluonic condensate $G_2$ with high accuracy if the gluonic correlation length $T_g$ is fixed. In our calculations the negative value of $\Delta_{\rm HF} = -0.3 \pm 0.4$ MeV is obtained only if the relatively small $T_g = 0.16$ fm and $G_2 = 0.065 (3)$ GeV${}^4$ are taken. These values correspond to the ``physical'' string tension $(\sigma \approx 0.18$ GeV$^2$). For $T_g \ge 0.2$ fm the hyperfine splitting is positive and grows for increasing $T_g$. In particular for $T_g = 0.2$ fm and $G_2 = 0.041 (2)$ GeV${}^4$ the splitting $\Delta_{\rm HF} = 1.4 (2)$ MeV is obtained, which is in accord with the recent CLEO result.Comment: 9 pages revtex 4, no figure

On the Particle Data Group evaluation of Psi' and chi_c Branching Ratios

I propose a new evaluation of $\psi'(2S)$ and $\chi_c(1P)$ branching ratios which avoids the correlations affecting the current Particle Data Group evaluation. These correlations explain the apparent technique-dependent discrepancies between the available determinations of the ${\cal B}(\chi_c(1P)\to p\bar p)$ and $\Gamma(\chi_c(1P)\to \gamma\gamma)$ under the hypotesis that the current values of the $\psi'(2S)\to\chi_c(1P)\gamma$ branching ratios are overestimated. In the process I also noticed that Particle Data Group has not restated many of the older measurements, when necessary, for the new value of ${\cal B}(J/\psi\to l^+l^-)$, which significantly affects the evaluation of some relevant $\psi'(2S)$ and $\chi_c(1P)$ exclusive branching ratios.Comment: 13 pages. Revised version. Submitted to Phys. Rev.

新収作品 : ジョルジュ・ド・ラ・トゥール《聖トマス》

We present a tomographic technique making use of a gigaelectronvolt electron beam for the determination of the material budget distribution of centimeter-sized objects by means of simulations and measurements. In both cases, the trajectory of electrons traversing a sample under test is reconstructed using a pixel beam-telescope. The width of the deflection angle distribution of electrons undergoing multiple Coulomb scattering at the sample is estimated. Basing the sinogram on position-resolved estimators enables the reconstruction of the original sample using an inverse radon transform. We exemplify the feasibility of this tomographic technique via simulations of two structured cubes—made of aluminium and lead—and via an in-beam measured coaxial adapter. The simulations yield images with FWHM edge resolutions of (177 ± 13) μm and a contrast-to-noise ratio of 5.6 ± 0.2 (7.8 ± 0.3) for aluminium (lead) compared to air. The tomographic reconstruction of a coaxial adapter serves as experimental evidence of the technique and yields a contrast-to-noise ratio of 15.3 ± 1.0 and a FWHM edge resolution of (117 ± 4) μm

A class of pyrrole derivatives endowed with analgesic/anti-inflammatory activity

We report the synthesis and bio-pharmacological evaluation of a class of pyrrole derivatives featuring a small appendage fragment (carbaldehyde, oxime, nitrile) on the central core. Compound 1c proved to be extremely effective in vivo, showing an interesting anti-nociceptic profile that is comparable to reference compounds already marketed, hence representing a great stimulus for a further improvement of this class of molecules

Improving the solubility of a new class of antiinflammatory pharmacodynamic hybrids, that release nitric oxide and inhibit cycloxygenase-2 isoenzyme

The development of a novel class of pharmacodynamic hybrids that inhibits COX-2 isoform is reported. These molecules display enhanced nitric oxide releasing properties due to the presence of an ionisable moiety. The in vivo analgesic/anti-inflammatory activity was maintained in relation to the parent compounds