Herein we describe our recent attempts to target the P2X₇ receptor for potential treatment of neurological disorders. This work focusses on different polycycles including carborane, adamantane or cubane, joined by either a cyanoguanidine or an amide linker to phenyl or isoquinoline moieties. We have demonstrated the superiority of the adamantyl moiety over other polycycles in terms of synthetic accessibility and biological (cellular) activity. We have also shown that an amide or cyanoguanidine linker can greatly alter the biological activity of compounds. This SAR study provides important insights into the types of functionality required to target the P2X₇ receptor.

本文中，我们描述了我们最近针对P2X ₇受体进行神经疾病潜在治疗的尝试。这项工作着眼于不同的多环化合物，包括碳硼烷，金刚烷或古巴，并通过氰基胍或酰胺连接基与苯基或异喹啉部分连接。我们已经证明了金刚烷基部分在合成可及性和生物（细胞）活性方面优于其他多环化合物。我们还表明，酰胺或氰基胍连接基可以大大改变化合物的生物活性。这项SAR研究为靶向P2X ₇受体所需的功能类型提供了重要的见识。