Discovery of 4-arylthiophene-3-carboxylic acid as inhibitor of ANO1 and its effect as analgesic agent.

Author: Yuxi WANG ¹ ; Jian GAO ¹ ; Song ZHAO ² ; Yan SONG ¹ ; Han HUANG ¹ ; Guiwang ZHU ¹ ; Peili JIAO ¹ ; Xiangqing XU ² ; Guisen ZHANG ³ ; Kewei WANG ⁴ ; Liangren ZHANG ¹ ; Zhenming LIU ¹
Author Information

1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
2. Jiangsu Nhwa Pharmaceutical Co., Ltd., Xuzhou 221116, China.
3. College of Life Science and Technology, Jiangsu Ocean University, Lianyungang 222005, China.
4. Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, China.
Publication Type:Journal Article
Keywords: ANO1 (anoctamin 1, TMEM16A); Analgesia; Inhibitor; Structure–activity relationship; Synthesis
From: Acta Pharmaceutica Sinica B 2021;11(7):1947-1964
CountryChina
Language:English
Abstract: Anoctamin 1 (ANO1) is a kind of calcium-activated chloride channel involved in nerve depolarization. ANO1 inhibitors display significant analgesic activity by the local peripheral and intrathecal administration. In this study, several thiophenecarboxylic acid and benzoic acid derivatives were identified as novel ANO1 inhibitors through the shape-based virtual screening, among which the 4-arylthiophene-3-carboxylic acid analogues with the best ANO1 inhibitory activity were designed, synthesized and compound