Filgotinib is a selective JAK1 (Janus kinase) inhibitor, filed in Japan for the treatment of rheumatoid arthritis. In this paper, we report a validated liquid chromatography coupled with tandem mass spectrometry for the quantification of filgotinib in rat plasma using tofacitinib as an internal standard (IS) as per the Food and Drug Administration regulatory guidelines. Filgotinib and the IS were extracted from rat plasma using ethyl acetate as an extraction solvent and chromatographed using an isocratic mobile phase (0.2% formic acid:acetonitrile; 20:80, v/v) at a flow rate of 0.9 mL/min on a Gemini C18 column. Filgotinib and the IS were eluted at ~1.31 and 0.89 min, respectively. The MS/MS ion transitions monitored were m/z 426.3 → 291.3 and m/z 313.2 → 149.2 for filgotinib and the IS, respectively. The calibration range was 0.78–1924 ng/mL. No matrix effect and carryover were observed. Intra- and inter-day accuracies and precisions were within the acceptance range. Filgotinib was stable for three freeze–thaw cycles: on bench-top up to 6 h, in an autosampler up to 21 h, and at −80 ° C for 1 month. This novel method has been applied to a pharmacokinetic study in rats. 相似文献
Functionalization of 2,1,3-benzothiadiazole (BTD) with thiols at C-5 position remains low explored. Moreover, the arylthiol-substitutions at this position are also unexplored and can not be found by a SN2 or SN1 reaction. In this sense, herein we present a new palladium-catalyzed methodology for a wide variety of unpublished 5-arylsulfanyl-benzo-2,1,3-thiadiazole derivatives synthesis with moderate to high yields using a low catalytic loading of Pd(L-Pro)2 as low-coast, and efficient catalyst in low reaction time. Besides, we concluded that the pKa of thiol species has an important role in this catalysis, mainly in the CMD like catalytic cyclo process, which strongly interferes in the reaction yields. Furthermore, arylsulfanyl-benzo-2,1,3-thiadiazoles derivatives have been assessed (in vitro) as potential acetylcholinesterase inhibitors. 相似文献
An agro waste‐derived, ‘water extract of pomegranate ash’ (WEPA), has been utilized for the first time as a renewable medium for Pd(OAc)2‐catalysed Suzuki–Miyaura cross‐coupling at room temperature. This method offers a simple and sustainable synthesis of biaryls from aryl halides and arylboronic acids under ligand‐ and external base‐free aerobic and ambient conditions. This method has been found effective for both activated and unactivated aryl halides in the production of biaryls with moderate to nearly quantitative yields. The protocol shows high chemoselectivity over identical/similar reactive sites in aryl halides (i.e. selectivity over identical halogens or different halogens of aryl halides). This method exhibits high regioselectivity, i.e. the selective reactivity of a halogen over other identical halogens at different positions on the aromatic nucleus. Therefore, we disclose here a clean, benign, substantial chemo‐ and regioselective and highly economic alternative method for the palladium‐assisted synthesis of biaryls using an agro waste‐derived medium. 相似文献
In this work, we investigate the electrical, structural, and thermal properties of composite polymer electrolytes (CPEs). Different mass fractions of antimony trioxide filler, Sb2O3, are added into poly(acrylic acid) (PAA)-based polymer electrolytes with N-lithiotrifluoromethane sulphonamide [LiN(SO2CF3)2] (LiTFSI) as doping salt. Characteristics such as alternating current (AC)–impedance spectroscopy, attenuated total reflectance–Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) are analyzed. The highest ionic conductivity of (2.15?±?0.01)?×?10?4 S cm?1 is achieved at room temperature with addition of 6 wt% of fillers. The ionic transportation is further proven in a transference number study under DC polarization, whereas ATR-FTIR is employed to explore the complexation between PAA, LiTFSI, and Sb2O3. TGA reveals the improved thermal stability of CPEs. The glass transition temperature (Tg) is reduced upon addition of Sb2O3 as shown in DSC analysis. 相似文献
A leading-edge suction parameter (LESP) that is derived from potential flow theory as a measure of suction at the airfoil leading edge is used to study initiation of leading-edge vortex (LEV) formation in this article. The LESP hypothesis is presented, which states that LEV formation in unsteady flows for specified airfoil shape and Reynolds number occurs at a critical constant value of LESP, regardless of motion kinematics. This hypothesis is tested and validated against a large set of data from CFD and experimental studies of flows with LEV formation. The hypothesis is seen to hold except in cases with slow-rate kinematics which evince significant trailing-edge separation (which refers here to separation leading to reversed flow on the aft portion of the upper surface), thereby establishing the envelope of validity. The implication is that the critical LESP value for an airfoil–Reynolds number combination may be calibrated using CFD or experiment for just one motion and then employed to predict LEV initiation for any other (fast-rate) motion. It is also shown that the LESP concept may be used in an inverse mode to generate motion kinematics that would either prevent LEV formation or trigger the same as per aerodynamic requirements. 相似文献
In the pursuit of new antifungal compounds, five coproduced lipopeptide variants (AF1 to AF5) from wild-type Bacillus subtilis RLID 12.1 were identified in our previous study. Out of five, AF4 was identified as a novel lead molecule belonging to the bacillomycin family showing less cytotoxicity at its respective minimum inhibitory concentrations (MIC) evaluated against 81 strains of Candida and Cryptococcus species (including clinical isolates); besides this, AF4 purified in the present study exhibited encouraging MIC values against 10 clinical mycelial fungi. Aiming for a selective production augmentation of AF4 lipopeptide variant, a new fermentation media comprising malt extract (1.01%), dextrose (0.55%), peptone (1.79%), MnSO4 (2 mM), and NaCl (0.5%) was formulated. Maximum production of 954.8?±?10.8 mg/L was achieved with 44% selectivity at 30 °C compared to unoptimized conditions (186.4?±?6.1 mg/L). Use of calcium alginate beads in the formulated media during the onset of lipopeptide production resulted in an augmentation in the selectivity of the most efficacious AF4 variant to about 72% presumably due to attenuation of other coproduced lipopeptide variants AF1 and AF2. Difference in yield of lipopeptides varied with bead size, bead preparation ratios, and sodium alginate concentrations. Use of Ca-alginate beads in the upstream production process of the lead AF4 variant may be considered as a novel strategy to address the potential challenge that may arise during the scale-up and downstream processing steps. Another significant finding derived from the study is that the proportion of bacillomycin variants of B. subtilis RLID 12.1 could be controlled by temperature and metal ions under static and shaking conditions. 相似文献
Nickel oxide (NiO) was synthesized via a one-step facile method. X-ray diffraction analysis confirmed the face-centered cubic structure of NiO. The bonding nature and surface purity were confirmed via Fourier-transform infrared spectroscopy. NiO revealed partial spherical morphology with less particle aggregation. The optical bandgap of NiO was found to be 3.75 eV. Cyclic voltammetry revealed well-defined oxidation and reduction peaks for NiO. The charge–discharge curve exhibited specific capacitance of 184.6 F/g at current density of 0.3 A/g. NiO electrode exhibited longer cyclic stability of 93 % up to 1500 cycles. In addition, NiO + H2O2 revealed efficient photocatalytic degradation of methylene blue (organic pollutant) under visible-light irradiation with degradation efficiency of ~88 %. These results confirm that nanosized NiO is more suitable for dual application.