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The angiotensin II type 2 receptor (AT 2 R) has attracted much attention as a potential target for the relief of neuropathic pain, which represents an area of unmet clinical need. A series of 1,2,3,4-tetrahydroisoquinolines with a benzoxazole side-chain were discovered as potent AT 2 R antagonists. Rational optimization resulted in compound 15 , which demonstrated both excellent antagonistic activity against AT 2 R in vitro and analgesic efficacy in a rat chronic constriction injury model. Its favorable physicochemical properties and oral bioavailability make it a promising therapeutic candidate for neuropathic pain.

Discovery and Optimization of Highly Potent and Selective AT2R Antagonists to Relieve Peripheral Neuropathic Pain

Discovery and Optimization of Highly Potent and Selective AT₂R Antagonists to Relieve Peripheral Neuropathic Pain