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Review Article

2011~2021年批准的GPCR靶向药物的构效关系

卷 30, 期 31, 2023

发表于: 19 December, 2022

页: [3527 - 3549] 页: 23

弟呕挨: 10.2174/1573399819666221102113217

价格: $65

Open Access Journals Promotions 2
摘要

背景：G蛋白偶联受体(GPCR)是最大的膜受体家族，也是研究最深入的药物靶点。鉴于GPCR信号转导在生理上的重要性以及近年来在膜蛋白结构测定方面的进展，GPCR拮抗剂和激动剂的开发有望继续成为药物化学研究的一个重要领域。 方法：构效关系说明了化学结构的改变如何影响药物化合物的吸收、分布、代谢、排泄和其他相关性质。了解临床批准的GPCR靶向药物及其类似物的结构-性质关系可以为候选药物的先导优化策略提供有用的信息。 结果：在过去十年批准的50多种GPCR拮抗剂和激动剂中，从药物化学文献中整理了17种药物的构效关系，其中不仅披露了最终候选药物的详细药代动力学和毒理学性质，还披露了在先导优化过程中产生的关键类似物。 结论：本文总结的构效关系表明，在许多情况下，膜蛋白靶向配体的体外和体内性能可以有效优化，而不需要显著改变分子大小。这一信息有望为加快新的GPCR靶向药物的开发提供有价值的见解。

关键词: 构效关系，GPCR拮抗剂，GPCR激动剂，先导物优化，候选物选择，药物发现。

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