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Review Article

酪氨酸激酶抑制剂先导物优化结构修饰策略探索新型抗癌药物的研究进展

卷 30, 期 24, 2023

发表于: 02 November, 2022

页: [2734 - 2761] 页: 28

弟呕挨: 10.2174/0929867329666220920092908

价格: $65

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摘要

先导化合物优化作为药物发现过程中的瓶颈，旨在解决与不良药代动力学、耐药性不断出现、不良副作用和已知药物的药物相互作用相关的问题。由于多靶点酪氨酸激酶抑制剂（MTKI）在各种病理条件下的广泛应用，其结构的优化一直是药物化学研究的重点。目前的综述描述了支架跳跃、生物电子等排、基于结构和基于混合的药物设计方法在优化先导化合物中的应用，旨在提高其作为新药的实用性。然后，审查继续进行结构修改的例子，特别是市场上已有的多靶点药物。演示的示例涵盖了过去 20 年中 7 种知名药物的结构修饰。上述策略的应用导致了 52 种新的多靶点酪氨酸激酶抑制剂的产生。与其母体先导化合物相比，大多数优化化合物显示出改进的性能。讨论了应用修改背后的基本原理和取得的成果，以向从事该领域的研究人员提供实际示例。

关键词: 结构修饰、杂交、酪氨酸激酶抑制剂、先导优化、药物发现、抗癌剂。

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