癫痫是常见的中枢神经系统疾病。对癫痫的经典治疗机理集中在经由调节神经递质谷氨酸和γ-氨基丁酸从而抑制中枢神经系统的超兴奋状态。遗憾的是，经由该作用机制的抗癫痫药物对超过30%的患者疗效不佳。另一方面，与受体的变构位点发生特异选择性结合从而调节内源性配体与受体的生物效力的变构调节剂因其安全、高效的特点近年来已受到药物化学家的广泛关注。因此发展经由新靶点和新配体-受体作用机制的安全、高效抗癫痫药物具有非常重要的研究意义。本课题拟在前期研究工作基础上，以非选择性神经多肽Galanin受体激动剂Galnon作为先导化合物，对其进行结构修饰和改造，设计合成一系列新型小分子G蛋白偶联受体GalR1/R2正性变构调节剂；通过测试反馈的体外生物活性数据，建立分析化合物的构效关系（SAR）；在此基础上，进一步优化分子的理化功能；最终拟筛选得到2-3个关键化合物，为下一步开展体内动物模型实验研究提供物质基础。

Affecting over 50 million patients all over the world, epilepsy is a common disease of the central nervous system (CNS) that can cause severe brain damage or even death. Previous efforts in the development of drugs targeting the classic neurotransmitters has only met with limited success. A groundbreaking, new approach for the treatment of epilepsy has been discovered in the applicant's previous research work, which has demonstrated the feasibility to effectively control epilepsy by molecules that allosterically modulate the fundamentally important interactions between neuropeptide Galanin and its receptors in the CNS. Based on this preliminary success, this project will develop molecules bearing novel structural features with improved physicochemical properties as well as higher biological efficacies suitable for in vitro test, eventually leading to the development of novel lead compounds for further in vivo studies.