Shenzhen Borui Pharmaceutical Technology Co., Ltd., Shenzhen 518055, China.
Medi-X Pingshan, Southern University of Science and Technology, Shenzhen 518055, China.
Molecules. 2024 Feb 2;29(3):689. doi: 10.3390/molecules29030689.
Natural bioactive compounds are valuable resources for drug discovery due to their diverse and unique structures. However, these compounds often lack optimal drug-like properties. Therefore, structural optimization is a crucial step in the drug development process. By employing medicinal chemistry principles, targeted molecular operations can be applied to natural products while considering their size and complexity. Various strategies, including structural fragmentation, elimination of redundant atoms or groups, and exploration of structure-activity relationships, are utilized. Furthermore, improvements in physicochemical properties, chemical and metabolic stability, biophysical properties, and pharmacokinetic properties are sought after. This article provides a concise analysis of the process of modifying a few marketed drugs as illustrative examples.
天然生物活性化合物因其多样且独特的结构而成为药物发现的宝贵资源。然而，这些化合物往往缺乏理想的药物样特性。因此，结构优化是药物开发过程中的关键步骤。通过运用药物化学原理，可以针对天然产物进行靶向分子操作，同时考虑其大小和复杂性。各种策略，包括结构碎片化、去除冗余原子或基团，以及探索结构-活性关系，都被应用。此外，还致力于改善物理化学性质、化学和代谢稳定性、生物物理性质以及药代动力学性质。本文通过简要分析几个已上市药物的修饰过程，为您提供示例说明。
