公开(公告)号：US20250122148A1

公开(公告)日：2025-04-17

申请号：US18728641

申请日：2023-01-10

Applicant: SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

Inventor： Fajun NAN ,  Zhaobing GAO ,  Wuheng DONG ,  Yueming ZHENG ,  Jintao WANG ,  Xiaoyu ZHOU ,  Huanan LIU ,  Haiyan XU

IPC: C07C269/04 ,  A61K31/27 ,  A61P21/00

Abstract: Disclosed are a high-selectivity KCNQ4 potassium channel agonist of formula I, a preparation method therefor and the use thereof. The compound further improves the KCNQ4 agonistic activity, and is still free of KCNQ2 agonistic activity, thus having excellent KCNQ4/KCNQ2 selectivity. The high-selectivity KCNQ4 agonist overcomes the defect of poor selectivity of existing potassium channel agonists, the activity is relatively increased, and the toxicity is remarkably reduced. The agonist also has a simpler structure and lower product cost, thereby having a better development prospect.

公开(公告)号：US20240270745A1

公开(公告)日：2024-08-15

申请号：US18569434

申请日：2022-06-15

Applicant: SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES ,  LANZHOU INSTITUTE OF CHEMICAL PHYSICS, CHINESE ACADEMY OF SCIENCES

Inventor： Zhaobing GAO ,  Junli YANG ,  Xianhua MENG ,  Yueming ZHENG ,  Tian CHAI ,  Yin ZHANG

IPC: C07D471/14 ,  A61K31/519 ,  A61P29/00

CPC classification number: C07D471/14 ,  A61K31/519 ,  A61P29/00

Abstract: Provided in the present invention are an isoquinoline alkaloid compound selected from the group consisting of the compounds represented by the following structural formulas, and a preparation method therefor and the use thereof. The present invention proves for the first time that the isoquinoline alkaloid compound is an inhibitor of the IK potassium current and the background potassium current in the nervous system, the cardiovascular system and the pancreas, especially an inhibitor of the Kv2.1 channel and the TRESK channel, and can be used for treating a disease such as stroke, arrhythmia, atrial fibrillation, diabetes, pain, hypoventilation, and depression.