Identification of 2-oxo-N-(phenylmethyl)-4-imidazolidinecarboxamide antagonists of the P2X(7) receptor.

Abstract A backup molecule to compound 2 was sought by targeting the most likely metabolically vulnerable site in this molecule. Compound 18 was subsequently identified as a potent P2X 7 antagonist with very low in vivo clearance and high oral bioavailability in all species examined. Some evidence to support the role of P2X 7 in the etiology of pain is also presented.