Isoindolin-1-one scaffolds represent a significant class of compounds in medicinal chemistry. This review provides a comprehensive overview of recent advancements in synthetic methodologies for isoindolin-1-one compounds. This review also discusses the pharmacological studies of isoindolin-1-one compounds along with structure–activity relationship studies.

Isoindolin-1-one scaffolds have emerged as privileged structures in medicinal and synthetic chemistry due to their diverse biological activities and synthetic accessibility. This review comprehensively highlights the recent advancements in the development of synthetic methodologies for constructing isoindolin-1-one cores, encompassing both metal-catalyzed and metal-free approaches. Key strategies include the electrochemical method, transition metal-catalyzed synthesis, radical and oxidant-driven metal-free method, acid-catalyzed and multicomponent method, ring opening method, and ultrasound-assisted method of synthesis. The flexibility of these methods arises from the wide range of starting materials, such as benzamides, imidates, nitriles, and aziridines, and the effective use of catalysts and additives, including Rh(III), Pd(II), Ru(II), Ag₂CO₃, CO, and various oxidants. This review also explores the structure–activity relationships of isoindolin-1-one derivatives in diverse therapeutic areas. Specific functional groups and substituents have been shown to enhance anticancer, antiviral, antipsychotic, antimicrobial, cardiovascular, anti-inflammatory, and antidiabetic activities. Modifications including lipophilic, electron-withdrawing, polar, and heterocyclic moieties have significantly improved biological efficacy, target specificity, and pharmacokinetics. The integration of these structural variations underscores the scaffold's versatility and its potential in drug discovery. This review aims to provide a consolidated foundation for future research on isoindolin-1-one based therapeutics and their strategic synthesis.