Synthesis and biological activity of a series of tetrasubstituted-imidazoles as P2X(7) antagonists.

@article{Gleave2010SynthesisAB,
  title={Synthesis and biological activity of a series of tetrasubstituted-imidazoles as P2X(7) antagonists.},
  author={Robert J Gleave and Daryl S. Walter and Paul J Beswick and Elena Fonfr{\'i}a and Anton D. Michel and Shilina A Roman and Sac-Pham Tang},
  journal={Bioorganic & medicinal chemistry letters},
  year={2010},
  volume={20 16},
  pages={4951-4}
}
A series of analogues of the pyrazole lead 1 were synthesized in which the heterocyclic core was replaced with an imidazole. A number of potent antagonists were identified and structure-activity relationships (SAR) were investigated both with respect to activity at the P2X(7) receptor and in vitro metabolic stability. Compound 10 was identified as a potent P2X(7) antagonist with reduced in vitro metabolism and high solubility.