(+)-and (−)-Lesinurad were isolated as atropisomers from racemic lesinurad for the first time. No interconversion was observed between the two atropisomers under various conditions tested. The two atropisomers showed significant differences in hURAT1 highly expressed HEK293 cell-based inhibition assays, monkey pharmacokinetic studies, and in vitro human recombinant CYP2C9 stability studies. It was speculated that (+)-lesinurad might offer a better hyperuricemia/gout therapy than (−)-lesinurad or the racemate.

No abstract

Introduction of a Michael acceptor on a flexible scaffold derived from pan-FGFR inhibitors has successfully yielded a novel series of highly potent FGFR4 inhibitors with selectivity over FGFR1. Due to reduced lipophilicity and aromatic ring count, this series demonstrated improved solubility and permeability. However, plasma instability and fast metabolism limited its potential for in vivo studies. Efforts have been made to address these problems, which led to the discovery of compound (-)-11 with improved stability, CYP inhibition, and good activity/selectivity for further optimization.

No abstract

Microdeep drawing has great potential in microsystem technologies, electron industries, new energy, etc. Microsquare cups with internal side length of 1 mm were formed in this study. The blank material was pure copper C1100 with a thickness of 50 μm which was annealed in vacuum condition at 573 and 723 K for 1 h, respectively. The experiments were conducted with an electronic universal testing machine. Three kinds of different lubrication conditions and blank holder force (BHF) were used, and the experimental velocity was 0.05 mm/s. The results showed that a microsquare cup with a limiting drawing ratio (LDR) of 1.89 was well formed. Compared to the as-received blank, the annealed blank decreased the drawing force and the earings and increased the LDR. The polyethylene (PE) film, which decreased the drawing force and increased the LDR, was much better than other lubrication conditions. The wrinkles decreased with the increase of the BHF under a specific value.