5,845 research outputs found
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
Novel ester and acid derivatives of the 1,5-diarylpyrrole scaffold as anti-inflammatory and analgesic agents. Synthesis and in vitro and in vivo biological evaluation.
A new generation of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) was developed to circumvent the major side effects of cyclooxygenase-1 (COX-1) and COX-2 inhibitors (stomach ulceration and nephrotoxicity). As a consequence, coxibs are extremely valuable in treating acute and chronic inflammatory conditions. However, the use of coxibs, such as rofecoxib (Vioxx), was discontinued because of the high risk of cardiovascular adverse events. More recent clinical findings highlighted how the cardiovascular toxicity of coxibs could be mitigated by an appropriate COX-1 versus COX-2 selectivity. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, selective for COX-2. Here, we describe the synthesis of new1,5-diarylpyrroles along with their inhibitory effects in vitro, ex vivo, and in vivo toward COX isoenzymes and their analgesic activity. Isopropyl-2-methyl-5-[4- (methylsulfonyl)phenyl]-1-phenyl-1H-pyrrole-3-acetate (10a), a representative member of the series, was selected for pharmacokinetic and metabolic studies
Novel ester and acid derivatives of the 1,5-diarylpyrrole scaffold as anti-inflammatory and analgesic agents. Synthesis and in vitro and in vivo biological evaluation.
A new generation of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) was developed to circumvent the major side effects of cyclooxygenase-1 (COX-1) and COX-2 inhibitors (stomach ulceration and nephrotoxicity). As a consequence, coxibs are extremely valuable in treating acute and chronic inflammatory conditions. However, the use of coxibs, such as rofecoxib (Vioxx), was discontinued because of the high risk of cardiovascular adverse events. More recent clinical findings highlighted how the cardiovascular toxicity of coxibs could be mitigated by an appropriate COX-1 versus COX-2 selectivity. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, selective for COX-2. Here, we describe the synthesis of new 1,5-diarylpyrroles along with their inhibitory effects in vitro, ex vivo, and in vivo toward COX isoenzymes and their analgesic activity. Isopropyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1H-pyrrole-3-acetate (10a), a representative member of the series, was selected for pharmacokinetic and metabolic studies
Operational experience with the GEM detector assembly lines for the CMS forward muon upgrade
The CMS Collaboration has been developing large-area triple-gas electron multiplier (GEM) detectors to be installed in the muon Endcap regions of the CMS experiment in 2019 to maintain forward muon trigger and tracking performance at the High-Luminosity upgrade of the Large Hadron Collider (LHC); 10 preproduction detectors were built at CERN to commission the first assembly line and the quality controls (QCs). These were installed in the CMS detector in early 2017 and participated in the 2017 LHC run. The collaboration has prepared several additional assembly and QC lines for distributed mass production of 160 GEM detectors at various sites worldwide. In 2017, these additional production sites have optimized construction techniques and QC procedures and validated them against common specifications by constructing additional preproduction detectors. Using the specific experience from one production site as an example, we discuss how the QCs make use of independent hardware and trained personnel to ensure fast and reliable production. Preliminary results on the construction status of CMS GEM detectors are presented with details of the assembly sites involvement
Search for R-parity violating supersymmetry via the LLE couplings lambda_{121}, lambda_{122} or lambda_{133} in ppbar collisions at sqrt(s)=1.96 TeV
A search for gaugino pair production with a trilepton signature in the
framework of R-parity violating supersymmetry via the couplings lambda_121,
lambda_122, or lambda_133 is presented. The data, corresponding to an
integrated luminosity of L~360/pb, were collected from April 2002 to August
2004 with the D0 detector at the Fermilab Tevatron Collider, at a
center-of-mass energy of sqrt(s)=1.96 TeV. This analysis considers final states
with three charged leptons with the flavor combinations eel, mumul, and eetau
(l=e or mu). No evidence for supersymmetry is found and limits at the 95%
confidence level are set on the gaugino pair production cross section and lower
bounds on the masses of the lightest neutralino and chargino are derived in two
supersymmetric models.Comment: 9 pages, 4 figures (fig2 includes 3 subfigures
Measurement of the Lifetime Difference in the B_s^0 System
We present a study of the decay B_s^0 -> J/psi phi We obtain the CP-odd
fraction in the final state at time zero, R_perp = 0.16 +/- 0.10 (stat) +/-
0.02 (syst), the average lifetime of the (B_s, B_sbar) system, tau (B_s^0)
=1.39^{+0.13}_{-0.16} (stat) ^{+0.01}_{-0.02} (syst) ps, and the relative width
difference between the heavy and light mass eigenstates, Delta Gamma/Gamma =
(Gamma_L - Gamma_H)/Gamma =0.24^{+0.28}_{-0.38} (stat) ^{+0.03}_{-0.04} (syst).
With the additional constraint from the world average of the B_s^0$lifetime
measurements using semileptonic decays, we find tau (B_s^0)= 1.39 +/- 0.06 ~ps
and Delta Gamma/\Gamma = 0.25^{+0.14}_{-0.15}. For the ratio of the B_s^0 and
B^0 lifetimes we obtain tau(B_s^0)/tau(B^0)} = 0.91 +/- 0.09 (stat) +/- 0.003
(syst).Comment: submitted to Phys. Rev. Lett. FERMILAB-PUB-05-324-
Measurement of Semileptonic Branching Fractions of B Mesons to Narrow D** States
Using the data accumulated in 2002-2004 with the DO detector in
proton-antiproton collisions at the Fermilab Tevatron collider with
centre-of-mass energy 1.96 TeV, the branching fractions of the decays B ->
\bar{D}_1^0(2420) \mu^+ \nu_\mu X and B -> \bar{D}_2^{*0}(2460) \mu^+ \nu_\mu X
and their ratio have been measured: BR(\bar{b}->B) \cdot BR(B-> \bar{D}_1^0
\mu^+ \nu_\mu X) \cdot BR(\bar{D}_1^0 -> D*- pi+) =
(0.087+-0.007(stat)+-0.014(syst))%; BR(\bar{b}->B)\cdot BR(B->D_2^{*0} \mu^+
\nu_\mu X) \cdot BR(\bar{D}_2^{*0} -> D*- \pi^+) =
(0.035+-0.007(stat)+-0.008(syst))%; and (BR(B -> \bar{D}_2^{*0} \mu^+ \nu_\mu
X)BR(D2*0->D*- pi+)) / (BR(B -> \bar{D}_1^{0} \mu^+ \nu_\mu X)\cdot
BR(\bar{D}_1^{0}->D*- \pi^+)) = 0.39+-0.09(stat)+-0.12(syst), where the charge
conjugated states are always implied.Comment: submitted to Phys. Rev. Let
Search for right-handed W bosons in top quark decay
We present a measurement of the fraction f+ of right-handed W bosons produced
in top quark decays, based on a candidate sample of events in the
lepton+jets decay mode. These data correspond to an integrated luminosity of
230pb^-1, collected by the DO detector at the Fermilab Tevatron
Collider at sqrt(s)=1.96 TeV. We use a constrained fit to reconstruct the
kinematics of the and decay products, which allows for the
measurement of the leptonic decay angle for each event. By comparing
the distribution from the data with those for the expected
background and signal for various values of f+, we find
f+=0.00+-0.13(stat)+-0.07(syst). This measurement is consistent with the
standard model prediction of f+=3.6x10^-4.Comment: Submitted to Physical Review D Rapid Communications 7 pages, 3
figure
Measurement of the ppbar to ttbar production cross section at sqrt(s)=1.96 TeV in the fully hadronic decay channel
A measurement of the top quark pair production cross section in proton
anti-proton collisions at an interaction energy of sqrt(s)=1.96 TeV is
presented. This analysis uses 405 pb-1 of data collected with the D0 detector
at the Fermilab Tevatron Collider. Fully hadronic ttbar decays with final
states of six or more jets are separated from the multijet background using
secondary vertex tagging and a neural network. The ttbar cross section is
measured as sigma(ttbar)=4.5 -1.9 +2.0 (stat) -1.1 +1.4 (syst) +/- 0.3 (lumi)
pb for a top quark mass of m(t) = 175 GeV/c^2.Comment: 10 pages, 10 figures, submitted to Phys. Rev.
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