Overview of Synthesis and Pharmacological Importance of Imidazole‐Based Polyheterocycles

Abstract Imidazole, a privileged heterocyclic scaffold, is widely incorporated into clinically used drugs and natural products due to its ability to engage in hydrogen bonding, π–π stacking, and coordination with metal ions. This review provides a comprehensive overview of imidazole‐based polyheterocycles, emphasizing their synthesis and diverse pharmacological potential. The article also discusses numerous clinically approved imidazole‐containing polyheterocycles such as quazinone, anagrelide, epinastine, midazolam, and flumazenil, highlighting their therapeutic roles. It further delves into naturally occurring fused imidazole derivatives like ageladine A, phakellins, grossularines, and cribrostatin 6, describing their isolation and total synthesis strategies. Additionally, recent advances in synthetic methodologies for constructing polyheterocyclic frameworks, such as imidazoquinazolines, imidazoquinoxalines, and imidazopyrimidines, are outlined. The review underscores the ongoing relevance of imidazole‐fused polyheterocycles in drug discovery and their potential for future therapeutic developments.