Synthesis and activity of N-cyanoguanidine-piperazine P2X7 antagonists

A novel series of cyanoguanidine-piperazine P2X(7) antagonists were identified and structure-activity relationship (SAR) studies described. Compounds were assayed for activity at human and rat P2X(7) receptors in addition to their ability to inhibit IL-1 beta release from stimulated human whole blood cultures. Compound 27 possesses potent activity (0.12 mu M) in this latter assay and demonstrates moderate clearance in-vivo. (C) 2008 Elsevier Ltd. All rights reserved.