先导化合物设计与开发

	先导化合物设计与开发
	Munikishore Rachakunta
导师	左之利
关键词	Buxus alkaloids Buxus alkaloids Cyclovirobuxine-D Cyclovirobuxine-D Synthesis, Calcium channel inhibitors Synthesis, Calcium channel inhibitors SAR studies SAR studies Anti-cardiovascular agents. Anti-cardiovascular agents.
摘要	ABSTRACT: Cyclovirobuxine D is a naturally occurring steroidal alkaloid and an active pharmaceutical ingredient of the CFDA-approved medication Huangyangning, which is used for treating multiple cardio and cerebrovascular indications. To develop further potent anti-cardiovascular derivatives, we synthesized five key fragments and two simplified analogues of the title compound using selective cleavage and structural modification strategies. Their structures were determined using spectroscopic methods. Compounds 2-5 and 7-8 were evaluated for their voltage-gated calcium channel inhibitory activities, and compound 2 was identified as the potent inhibitor of Cav3.1 current. Structure-activity relationship studies have suggested that the presence of an olefinic bond between C-9(11) positions is the most important factor influencing activity. This study identified compound 2 as a promising Cav3.1 inhibitor, a step in the exploration of powerful anti-cardiovascular agents.; ABSTRACT: Cyclovirobuxine D is a naturally occurring steroidal alkaloid and an active pharmaceutical ingredient of the CFDA-approved medication Huangyangning, which is used for treating multiple cardio and cerebrovascular indications. To develop further potent anti-cardiovascular derivatives, we synthesized five key fragments and two simplified analogues of the title compound using selective cleavage and structural modification strategies. Their structures were determined using spectroscopic methods. Compounds 2-5 and 7-8 were evaluated for their voltage-gated calcium channel inhibitory activities, and compound 2 was identified as the potent inhibitor of Cav3.1 current. Structure-activity relationship studies have suggested that the presence of an olefinic bond between C-9(11) positions is the most important factor influencing activity. This study identified compound 2 as a promising Cav3.1 inhibitor, a step in the exploration of powerful anti-cardiovascular agents.
语种	中文
	2022-06
学位授予单位	中国科学院大学
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75153
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	Munikishore Rachakunta. 先导化合物设计与开发[D]. 中国科学院大学,2022.

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