Discovery of benzamide derivatives containing urea moiety as soluble epoxide hydrolase inhibitors.

The elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) is efficient for the treatment of inflammatory and pain-related diseases. Herein, we reported the discovery of a series of benzamide derivatives containing urea moiety as sEH inhibitors. Intensive structural modifications led to the identification of compound A34 as a potent sEH inhibitor with good physicochemical properties. Molecular docking revealed an additional hydrogen-bonding interaction between the unique amide scaffold and Phe497, contributing to sEH inhibition potency enhancement. Compound A34 exhibited outstanding inhibitory activity against human sEH, with an IC50 value of 0.04 ± 0.01 nM and a Ki value of 0.2 ± 0.1 nM. It also showed moderate systemic drug exposure and oral bioavailability in vivo metabolism studies. In carrageenan-induced inflammatory pain rat model, compound A34 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib. Metabolism studies in vivo together with an inflammatory pain evaluation suggest that A34 may be a viable lead compound for the development of highly potent sEH inhibitors.

Synthesis and biological evaluation of new series of benzamide derivatives containing urea moiety as sEH inhibitors.

The pharmacological inhibition of soluble epoxide hydrolase (sEH) was shown to reduce inflammation and pain. Herein, we described a series of newly synthesized sEH inhibitors with the trident-shaped skeleton. Intensive structural modifications led to the identification of compound B15 as a potent sEH inhibitor with an IC50 value of 0.03 ± 0.01 nM. Furthermore, compound B15 showed satisfactory metabolic stability in human liver microsomes with a half-time of 197 min. In carrageenan-induced inflammatory pain rat model, compound B15 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib, which demonstrated the proof of potential as anti-inflammatory agents for pain relief.

In Situ Electrochemical Transformation Reaction of Ammonium-Anchored Heptavanadate Cathode for Long-Life Aqueous Zinc-Ion Batteries.

Rechargeable aqueous zinc-ion batteries (ZIBs) are promising portable and large-scale grid energy storage devices, as they are safe and economical. However, developing suitable ZIB cathode materials with excellent cycling performance characteristics remains a challenging task. Here, ammonium heptavanadate (NH4)2V7O16·3.2H2O (NHVO) nanosquares with mixed-valence V5+/V4+ as a cathode are developed for high-performance ZIBs. The layered NHVO shows a capacity of 362 mA h g-1 at 0.05 A g-1, with a high energy density of 263.5 W h kg-1. It exhibits an initial specific capacity of 250.7 mA h g-1 at a current density of 4 A g-1 and retains 255 mA h g-1 capacity after 1000 charge/discharge cycles. The V7O16-based cathode was demonstrated with a phase transition to the V2O5-based cathode upon initial cycling. Moreover, the in situ generated V2O5-based cathodes show excellent electrochemical properties, which provide a different perspective on the electrochemical reaction of cathode materials for aqueous ZIBs.

High-Performance Symmetric Supercapacitor Constructed Using Carbon Cloth Boosted by Engineering Oxygen-Containing Functional Groups.

Carbon materials display appealing physical, chemical, and mechanical properties and have been extensively studied as supercapacitor electrodes. The surface engineering further allows us to tune their capability of adsorption/desorption and catalysis. Therefore, a facile and inexpensive chemical-acid-etching approach has been developed to activate the carbon cloth as an electrode for supercapacitor. The capacitance of the acid-etched carbon cloth electrode can approach 5310 mF cm-2 at a current density of 5 mA cm-2 with remarkable recycling stability. The all-solid-state symmetric supercapacitor delivered a high energy density of 4.27 mWh cm-3 at a power density of 1.32 W cm-3. Furthermore, this symmetric supercapacitor exhibited outstanding mechanical flexibility, and the capacity remained nearly unchanged after 1000 bending cycles.

Development and validation an LC-MS/MS method to quantify (+)-borneol in rat plasma: Application to a pharmacokinetic study.

(+)-Borneol, a bicyclic monoterpene, has been shown to possess valuable biological properties and potential as a pharmaceutical agent due to anti-inflammatory, anti-oxidant and GABA receptor-enhancing functions; it also enhances the permeability of the blood brain barrier to improve the efficacy of CNS drugs. In this study, we have developed a simple, selective, and rapid liquid chromatography-tandem mass spectrometry method for the assay of (+)-borneol in rat plasma. Verapamil was used as an internal standard. Plasma samples were deproteinized using methanol. The analyte was detected by a mass spectrometer with positive atmospheric pressure chemical ionization by multiple reaction monitoring mode for transitions at m/z [M + H]+ 137.2 → 81.0 for (+)-borneol and 455.2 → 165.1 for verapamil. The method has been fully validated to ensure good selectivity, a satisfactory lower limit of quantification at 10.0 ng/mL, acceptable intra- and inter-day accuracy, and high precision. The method was used for the pharmacokinetic evaluation of (+)-borneol in Sprague-Dawley rats after intravenous, oral, and sublingual administration. The results indicate that oral bioavailability of (+)-borneol was extremely low but sublingual administration yielded rapid absorption and favorable bioavailability of (+)-borneol.