Discovery and Optimization of Highly Potent and Selective AT 2 R Antagonists to Relieve Peripheral Neuropathic Pain

The angiotensin II type 2 receptor (AT 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 R antagonists. Rati...

Full description

Saved in:
Bibliographic Details
Published in:ACS omega 2021-06, Vol.6 (23), p.15412-15420
Main Authors: Guo, Yanghui, Huang, Xiangui, Liao, Weiwei, Meng, Lichen, Xu, Daiwang, Ye, Cheng, Chen, Lei, Hu, Taishan
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The angiotensin II type 2 receptor (AT 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 R antagonists. Rational optimization resulted in compound , which demonstrated both excellent antagonistic activity against AT R 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.
ISSN:2470-1343
2470-1343
DOI:10.1021/acsomega.1c01866