Open AccessDiscovery and Optimization of Highly Potent and Selective AT2R Antagonists to Relieve Peripheral Neuropathic Pain
Author(s) -
Yang-hui Guo,
Xian-gui Huang,
Weiwei Liao,
Lichen Meng,
Dongxin Xu,
Ya Cheng,
Lei Chen,
TaiShan Hu
Publication year - 2021
Publication title -
acs omega
Language(s) - English
Resource type - Journals
ISSN - 2470-1343
DOI - 10.1021/acsomega.1c01866
Subject(s) - neuropathic pain , pharmacology , medicine , analgesic , benzoxazole , chronic pain , bioavailability , anesthesia , chemistry , physical therapy , organic chemistry
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.