2020/12/31 by Kerstin Hiesinger, Dmitry Dar’in, Ewgenij Proschak +1 · 2 citations
Chemistry · Pharmacology, Toxicology and Pharmaceutics · #Synthesis and Biological Evaluation #Asymmetric Synthesis and Catalysis #Bioactive Compounds and Antitumor Agents
paper · doi:10.1021/acs.jmedchem.0c01473
openalex publication_date 2020/12/31 · openalex created_date 2021/01/05 · openalex updated_date 2026/07/22
Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest in less planar bioactive compounds has given rise to the development of synthetic methodologies for the preparation of spirocyclic scaffolds. In this Perspective, we summarize the diverse synthetic routes to obtain spirocyclic systems. The impact of spirocycles on potency and selectivity, including the aspect of stereochemistry, is discussed. Furthermore, we examine the changes in physicochemical properties as well as in in vitro and in vivo ADME using selected studies that compare spirocyclic compounds to their nonspirocyclic counterparts. In conclusion, the value of spirocyclic scaffolds in medicinal chemistry is discussed.