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Updated: Nov 1, 2025

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Discovery and Optimization of Highly Potent and Selective AT2R Antagonists to Relieve Peripheral Neuropathic Pain
Yanghui Guo1, Xiangui Huang1, Weiwei Liao1
1Shanghai Institute of Drug Discovery, Zhejiang Hisun Pharmaceutical Co., Ltd., Building 25, 301 Minqiang Road, Shanghai 201612, China.
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.
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