随着全球人口老龄化加剧,阿尔茨海默病已成为威胁人类健康的重大疾病之一。目前尚无明显改善该病患者认知功能的药物,是未被满足的医疗需求和极具挑战的研发方向。研究表明,增强α7型尼古丁乙酰胆碱受体(n ACh R)功能可改善认知障碍和...随着全球人口老龄化加剧,阿尔茨海默病已成为威胁人类健康的重大疾病之一。目前尚无明显改善该病患者认知功能的药物,是未被满足的医疗需求和极具挑战的研发方向。研究表明,增强α7型尼古丁乙酰胆碱受体(n ACh R)功能可改善认知障碍和神经免疫功能。与激动剂的作用方式不同,α7正向变构调节剂(α7 PAMs)仅增强内源性乙酰胆碱递质激活n ACh R的功能,具有不易产生脱敏和潜在毒副作用较小的特点,是潜在治疗阿尔茨海默病的新策略。结合文献和笔者所在课题组的近期研究工作,重点介绍α7 nAChR及其正向变构调节剂(α7 nAChR PAMs)的结构与生物学评价,以期推动能改善认知功能障碍的α7 nAChR PAMs的研发进程。展开更多
Palladium-catalyzed Suzuki carbonylation with CHCl3 as carbonylative reagent was realized without external ligands. Different substituted benzophenones were explored via the coupling reaction of aryl iodides, arylboro...Palladium-catalyzed Suzuki carbonylation with CHCl3 as carbonylative reagent was realized without external ligands. Different substituted benzophenones were explored via the coupling reaction of aryl iodides, arylboronic acids and CHCl3 as a CO surrogate in moderate to good yields. This method was also successfully applied to the structure modification of α7 nicotinic acetylcholine receptor positive allosteric modulators（α7 nAChR PAMs） based on the preliminary structure-activity relationship.展开更多
基金The National Natural Science Foundation of China(Grant No.21572011 and 21272009)
文摘Palladium-catalyzed Suzuki carbonylation with CHCl3 as carbonylative reagent was realized without external ligands. Different substituted benzophenones were explored via the coupling reaction of aryl iodides, arylboronic acids and CHCl3 as a CO surrogate in moderate to good yields. This method was also successfully applied to the structure modification of α7 nicotinic acetylcholine receptor positive allosteric modulators（α7 nAChR PAMs） based on the preliminary structure-activity relationship.
