High-selectivity KCNQ4 potassium channel agonist as well as preparation method and application thereof

• Main Authors: ZHENG YUEMING, XU HAIYAN, ZHOU XIAOYU, GAO ZHAOBING, WANG JINTAO, DONG WUHENG, LIU HUANAN, NAN FAJUN
• Format: Patent
• Language: Chinese; English
• Published: 25.07.2023
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The invention provides a high-selectivity KCNQ4 potassium channel agonist as shown in a formula I as well as a preparation method and application of the high-selectivity KCNQ4 potassium channel agonist. The compound provided by the invention not only further improves the KCNQ4 agonist activity, but also enables the KCNQ4 to lose the KCNQ2 agonist activity, and still has very good KCNQ4/KCNQ2 selectivity. The novel selective KCNQ4 agonist provided by the invention overcomes the defect of poor selectivity of the existing potassium channel agonist, and has the advantages of improved activity, obviously reduced toxicity, simpler structure and lower production cost, thereby having better development prospects. 本发明提供了一种式I所述的高选择性KCNQ4钾通道激动剂、其制备方法和用途。本发明的化合物不仅进一步提高KCNQ4激动活性，并且仍然使其丧失KCNQ2激动活性，依然具有很好的KCNQ4/KCNQ2选择性。本发明所提供的该类新型选择性KCNQ4激动剂克服了现有钾通道激动剂所存在的选择性不佳的缺点，活性有所提高，毒性明显降低，并且结构更加简单，生产成本更加低的优点，因此有着更好的发展前景。