Kinase array design, back to front: biaryl amides.

New kinase inhibitors can be found by synthesis of targeted arrays of compounds designed using system-based knowledge as well as through screening focused or diverse compounds. Most array strategies aim to add functionality to a fragment that binds in the purine subpocket of the ATP-site. Here, an alternative pharmacophore-guided array approach is described which set out to discover novel purine subpocket-binding groups.

Is continuous infusion ceftriaxone better than once-a-day dosing in intensive care? A randomized controlled pilot study.

Objectives: To compare the clinical and bacteriological outcome of critically ill patients with sepsis treated by ceftriaxone administered as a once-a-day intermittent bolus dose or by 24 h continuous infusion.

Patients And Methods: We conducted an open-label, randomized controlled pilot study in 57 patients clinically diagnosed with sepsis (suspected/proven infection and systemic inflammatory response syndrome) in a tertiary level intensive care unit. Patients were randomized to receive 2 g of ceftriaxone administered by once-daily intermittent bolus dosing or by 24 h continuous infusion.