报告题目：Design and Synthesis of Nicotinic Ligands for Use in Depression
报告人：章涵堃🐸，天美娱乐副教授
时 间：11月27日 11:45-12:45（周三）
地 点：闵行校区天美娱乐大楼159报告厅
报告人简介：
章涵堃💆🏿♂️，2002年本科毕业于中国药科大学化学制药专业，2009年获得中科院上海药物研究所药物化学博士学位🤍，之后在美国伊利诺伊大学芝加哥分校进行博士后研究。2013年7月进入天美娱乐工作。
报告内容简介：
Despite their discovery in the early 20th century and intensive study over the last twenty years, nicotinic acetylcholine receptors (nAChRs) are still far from being well understood. Only a few chemical entities targeting nAChRs are currently undergoing clinical trials, and even fewer have reached the marketplace. In our efforts to discover novel and truly selective nAChR ligands, we designed and synthesized a series of chiral cyclopropane-containing 42-specific ligands that display low nanomolar binding affinities and excellent subtype selectivity, while acting as partial agonists at 42-nAChRs. Their favorable antidepressant-like properties were demonstrated in the classical mouse forced swim test. Preliminary ADMET studies and broad screening towards other common neurotransmitter receptors were also carried out to further evaluate their safety profile and eliminate their potential off-target activity. These highly potent cyclopropane ligands possess superior subtype selectivity compared to other 42-nAChR agonists reported to date, including the marketed drug varenicline, and therefore may fully satisfy the crucial prerequisite for avoiding adverse side effects. These novel chemical entities could potentially be advanced to the clinic as new drug candidates for treating depression.
