The Most Common Functional Groups in Bioactive Molecules and How Their Popularity Has Evolved over Time

• Published in: Journal of medicinal chemistry Vol. 63; no. 15; pp. 8408 - 8418
• Main Authors: Ertl, Peter, Altmann, Eva, McKenna, Jeffrey M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 13.08.2020
• Subjects: Chemistry, Pharmaceutical - methods; Drug Design; Drug Discovery - methods; Ligands; Molecular Structure; Pharmaceutical Preparations - chemistry; Small Molecule Libraries - chemistry
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.0c00754

The concept of functional groups (FGs), sets of connected atoms that can determine the intrinsic reactivity of the parent molecule and in part are responsible for the overall properties of the molecule, form a foundation within modern medicinal chemistry. In this Article, we analyze the occurrence of various FGs in molecules described in the medicinal chemistry literature over the last 40 years and show how their development and utilization over time has varied. The popularity of various FGs has not evolved randomly, but instead, clear patterns of use are evident. Various factors influencing these patterns, including the introduction of new synthetic methods, novel techniques, and strategies applied in drug discovery and the better knowledge of molecular properties affecting the success of candidate development, are discussed.