Synthesis and in vitro activity of 1-(2,3-dichlorophenyl)-N-(pyridin-3-ylmethyl)-1H-1,2,4-triazol-5-amine and 4-(2,3-dichlorophenyl)-N-(pyridin-3-ylmethyl)-4H-1,2,4-triazol-3-amine P2X7 antagonists

A novel series of aminotriazole-based P2X7 antagonists was synthesized, and their structure–activity relationships (SAR) were investigated for activity at both human and rat P2X7 receptors. Most compounds showed greater potency at the human receptor although several analogs were discovered with potent activity (pIC50 ⩾ 7.5) at both human and rat P2X7.

Graphical abstractA novel series of aminotriazole-based P2X7 antagonists was synthesized. Most compounds showed greater potency at the human receptor although several analogs were discovered with potent activity (pIC50 ⩾ 7.5) at both human and rat P2X7.Figure optionsDownload full-size imageDownload as PowerPoint slide