Synthesis and activity of N-cyanoguanidine-piperazine P2X7 antagonists

A novel series of cyanoguanidine-piperazine P2X7 antagonists were identified and structure–activity relationship (SAR) studies described. Compounds were assayed for activity at human and rat P2X7 receptors in addition to their ability to inhibit IL-1β release from stimulated human whole blood cultures. Compound 27 possesses potent activity (0.12 μM) in this latter assay and demonstrates moderate clearance in-vivo.

Graphical abstractA novel series of cyanoguanidine-piperazine P2X7 antagonists were identified and structure–activity relationship (SAR) studies described. Compounds were assayed for activity at human and rat P2X7 receptors in addition to their ability to inhibit IL-1β release from stimulated human whole blood cultures. Compound 27 possesses potent activity (0.12 μM) in this latter assay and demonstrates moderate clearance in-vivo.Figure optionsDownload full-size imageDownload as PowerPoint slide