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

ABSTRACT: The angiotensin II type 2 receptor (AT₂R) 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 AT₂R antagonists. Rational optimization resulted in compound 15, which demonstrated both excellent antagonistic activity against AT₂R 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.

SUBMITTER: Guo Y

PROVIDER: S-EPMC8210434 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Guo Yanghui Y Huang Xiangui X Liao Weiwei W Meng Lichen L Xu Daiwang D Ye Cheng C Chen Lei L Hu Taishan T

ACS omega 20210528 23

The angiotensin II type 2 receptor (AT2R) 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 AT2R antagonists. Rational optimization resulted in compound 15, which demonstrated both excellent antagonistic activity against AT2R in vitro and analgesic efficacy in a rat ...[more]

PMID: 34151119

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