公开(公告)号：US20240051975A1

公开(公告)日：2024-02-15

申请号：US18258346

申请日：2022-02-14

申请人： TSINGHUA UNIVERSITY

发明人： Gelin WANG ,  Yefeng TANG ,  Hong YAO ,  Minghui LIU ,  Leibo WANG ,  Chenyu LI ,  Ruoxi ZHANG ,  Yumeng ZU ,  Chuo WU ,  Feifei LI ,  Shuangquan CHEN

IPC分类号： C07F5/02 ,  C07C235/24 ,  C07D213/65 ,  C07C255/50 ,  C07C311/16 ,  C07C279/04 ,  A61P25/28

CPC分类号： C07F5/025 ,  C07C235/24 ,  C07D213/65 ,  C07C255/50 ,  C07C311/16 ,  C07C279/04 ,  A61P25/28 ,  C07C2601/16

摘要： The present invention provides a class of novel NAMPT enzyme agonist and preparation and use thereof, which has a structural formula as shown in formula I or formula II. The present invention screens the NAMPT agonist NAT from the chemical small molecule library, and the NAT exhibits a good cytoprotective effect and a good anti-neurodegeneration effect in animal models of neurodegeneration. We studied the binding of NAT to enzymes, and then carried out multiple rounds of structure optimization based on the chemical structure characteristics of NAT and its enzyme activity properties, and obtained a relatively defined structure-activity relationship. The present patent not only lays the foundation for developing innovative drugs for anti-aging and neurodegenerative diseases, but also theoretically provides a proof-of-concept that enhancing NAMPT enzyme activity plays an important role in neuroprotection.