Variation of the aryl substituent on the piperazine ring within the 4-(piperazin-1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold unveils potent, non-competitive inhibitors of the inflammatory caspases.

The inflammatory caspases (caspase-1, -4 and -5) are potential therapeutic targets for autoimmune and inflammatory diseases due to their involvement in the immune response upon inflammasome formation. A series of small molecules based on the 4-(piperazin-1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold were synthesized with varying substituents on the piperazine ring. Several compounds were pan-selective inhibitors of the inflammatory caspases, caspase-1, -4 and -5, with the ethylbenzene derivative CK-1-41 displaying low nanomolar K values across this family of caspases.

Incidence, characteristics and management of pain in one operational area of medical emergency teams.

Background: Experience of pain associated with both chronic as well as acute medical conditions is a main cause for call for ambulance. The aim of this study was to establish both frequency and characteristics of pain reported by patients treated in pre-hospital environment in a single operational area. The supplementary goal was an analysis of methods of pain alleviation applied by medical personnel in the above described scenario.