Simulation-based evaluation of the Pharmpy Automatic Model Development tool for population pharmacokinetic modeling in early clinical drug development.

The Pharmpy Automatic Model Development (AMD) tool automates the building of population pharmacokinetic (popPK) models by utilizing a systematic stepwise process. In this study, the performance of the AMD tool was assessed using simulated datasets. Ten true models mimicking classical popPK models were created.

A Detailed Kinetico-Mechanistic Investigation on the Palladium C-H Bond Activation in Azobenzenes and Their Monopalladated Derivatives.

Palladium C-H bond activation in azobenzenes with R and R at positions of the phenyl rings (R = NMe, R = H (); R = NMe, R = Cl (); R = NMe, R = I (); R = NMe, R = NO (); R = H, R = H ()) and their monopalladated derivatives, using -[PdCl(DMF)], has been studied in detail by H NMR spectroscopy in -dimethylformamide- (DMF-) at room temperature; the same processes have been monitored in parallel via time-resolved UV-vis spectroscopy in DMF at different temperatures and pressures. The final goal was to achieve, from a kinetico-mechanistic perspective, a complete insight into previously reported reactivity results. The results suggest the operation of an electrophilic concerted metalation-deprotonation mechanism for both the mono- and dipalladation reactions, occurring from the coordination compound and the monopalladated intermediates, respectively.