Evaluations employing DEREK and P450 in silico metabolism indicate that slight alterations or replacements in the pyrrolidine moiety (98%) through drug development may improve the metabolic stability of novel derivatives relative to fedratinib.
Buparlisib exhibited a moderate extraction ratio, with a Clint of 32.24 mL min−1 kg−1 and a t1/2 of 25.15 min. Small changes of the 2-aminopyridine (58%) and morpholine (42%) moieties in buparlisib may increase stability and enhance safety profile.
The in vitro t1/2 (21.07 min) and Clint (38.48 mL min−1 kg−1) of omipalisib show that it exhibits a moderate extraction ratio. Minor changes to methoxy or pyridazine ring could enhance the safety and metabolic stability of omipalisib derivatives.
Metabolic stability research showed crenolanib's moderate extraction ratio. In silico software suggested that small piperidin-4-amine moiety alterations (99%) during drug development may improve metabolic stability.
Metabolic stability studies demonstrated moderate baricitinib extraction ratio. Minor adjustments to the pyrrole (88%) and pyrimidine (5%), during drug design, may increase novel derivatives' safety and metabolic stability compared to baricitinib.