School of Chemistry and Physics, Pietermaritzburg Campus, University of KwaZulu-Natal, Private Bag X01, Pietermaritzburg, Scottsville, 3209, South Africa.
ChemMedChem. 2021 Apr 20;16(8):1199-1225. doi: 10.1002/cmdc.202000929. Epub 2021 Feb 16.
Modern medicinal chemistry is a complex, multidimensional discipline that operates at the interface of the chemical and biological sciences. The medicinal chemistry contribution to drug discovery is typically described in the context of the well-recited linear progression of the drug discovery pipeline. However, compound optimization is idiosyncratic to each project, and clear definitions of hit and lead molecules and the subsequent progress along the pipeline becomes easily blurred. In addition, this description lacks insight into the entangled relationship between chemical and pharmacological properties, and thus provides limited guidance on how innovative medicinal chemistry strategies can be applied to solve optimization problems, regardless of the stage in the pipeline. Through discussion and illustrative examples, this article seeks to provide insights into the finesse of medicinal chemistry and the subtlety of balancing chemical properties pharmacology. In so doing, it aims to serve as an accessible and simple-to-digest guide for anyone who wishes to learn about the underlying principles of medicinal chemistry, in a context that has been decoupled from the pipeline description.
现代药物化学是一门复杂的、多维的学科，它在化学和生物科学的交界处运作。药物化学对药物发现的贡献通常是在药物发现管道的经典线性进展的背景下描述的。然而，化合物的优化对于每个项目都是特殊的，并且对于命中分子和先导分子的明确定义以及随后在管道中的进展变得容易模糊。此外，这种描述缺乏对化学和药理学性质之间复杂关系的洞察，因此对于如何应用创新的药物化学策略来解决优化问题提供的指导有限，而不管在管道的哪个阶段。通过讨论和举例说明，本文旨在深入了解药物化学的精妙之处，以及平衡化学性质药理学的微妙之处。通过这样做，它旨在为任何希望了解药物化学基本原理的人提供一个可访问且易于理解的指南，其内容与管道描述脱钩。
