Application of Pyrrolidine in FDA-Approved Drugs.

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 sp3 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.