先导化合物设计与开发
文献类型：学位论文
| 作者 | Munikishore Rachakunta |
| 答辩日期 | 2022-06 |
| 授予单位 | 中国科学院大学 |
| 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. |
| 英文摘要 | 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 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/75153]  |
| 专题 | 昆明植物研究所_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. |
入库方式： OAI收割
来源：昆明植物研究所
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