Synthesis of 9-(substituted phenoxycarbonyl)-10-methylacridinium trifluoromethanesulfonates: Effects of the leaving group on chemiluminescent properties.

Various 9-(substituted phenoxycarbonyl)-10-methylacridinium trifluoromethanesulfonates possessing electron-withdrawing substituents have been synthesized. The effect of substituents on the stability of the acridinium esters (AEs) at various temperatures in different buffers and the chemiluminescent properties have been examined. There was little correlation between the chemiluminescent properties of AEs and the pKa values of their associated phenols, but the steric effects of the ortho-substituents in the phenoxy group, as well as their electron-withdrawing natures, seem to play an important role in determining the properties.

Prediction of the liver safety profile of a first-in-class myeloperoxidase inhibitor using quantitative systems toxicology modeling.

The novel myeloperoxidase inhibitor verdiperstat was developed as a treatment for neuroinflammatory and neurodegenerative diseases. During development, a computational prediction of verdiperstat liver safety was performed using DILIsym v8A, a quantitative systems toxicology (QST) model of liver safety.A physiologically-based pharmacokinetic (PBPK) model of verdiperstat was constructed in GastroPlus 9.

Elevated Southern Hemisphere moisture availability during glacial periods.

Late Pleistocene ice-age climates are routinely characterized as having imposed moisture stress on low- to mid-latitude ecosystems. This idea is largely based on fossil pollen evidence for widespread, low-biomass glacial vegetation, interpreted as indicating climatic dryness. However, woody plant growth is inhibited under low atmospheric CO (refs.

Synthesis and chemiluminescent characteristics of two new acridinium esters.

Two new acridinium esters with a 2-(succinimidyloxycarbonyl)ethyl side arm, namely, 9-(2,6-dibromophenoxycarbonyl)-10-methyl-2-(2-(succinimidyloxycarbonyl)ethyl)acridinium trifluoromethanesulfonate and 9-(4-(2-(succinimidyloxycarbonyl)ethyl)phenoxycarbonyl)-2,7-dimethoxy-10-methylacridinium triflate, have been produced and characterized. The chemiluminescent properties and hydrolytic stabilities of the new acridinium esters have been investigated.