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

Autor:	Ye Cheng, Xiangui Huang, Chen Lei, Lichen Meng, Daiwang Xu, Liao Weiwei, Guo Yanghui, Hu Taishan
Rok vydání:	2021
Předmět:	business.industry General Chemical Engineering Analgesic General Chemistry Pharmacology Peripheral neuropathic pain Article Bioavailability Chemistry Constriction injury Neuropathic pain Medicine Angiotensin II Type-2 Receptor business QD1-999
Zdroj:	ACS Omega ACS Omega, Vol 6, Iss 23, Pp 15412-15420 (2021)
ISSN:	2470-1343
DOI:	10.1021/acsomega.1c01866
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::95908826daf14b67240cdf14ef8fd1c6 https://doi.org/10.1021/acsomega.1c01866 Zobrazit plný text záznamu