Application of Pyrrolidine in FDA‐Approved Drugs

ABSTRACT

The saturated five‐membered pyrrolidine ring is a privileged scaffold in medicinal chemistry. There is great interest in the pyrrolidine skeleton due to several key characteristics of this heterocyclic ring: its sp ³ hybridized carbon framework, the contribution of multiple chiral centers, and the inherent planarization of the ring, typically manifested as conformational flexibility or pseudorotation. These characteristics make pyrrolidine‐based structures highly attractive in the drug design for various biological targets. The pyrrolidine moiety also enhances drug‐like properties such as metabolic stability, water solubility, and modulation of basicity, and can interact favorably with a wide range of biological targets through specific stereochemical interactions. This review surveys the synthesis and clinical applications of FDA‐approved pyrrolidine‐containing drugs since 2014, with the aim of informing the rational design of next‐generation pyrrolidine‐based therapeutics.