2,5-Diazabicyclo[2.2.1]heptane in Medicinal Chemistry: A Treasure Trove of Therapeutic Opportunities

Abstract

2,5-Diazabicyclo[2.2.1]heptane (2,5-DBH) has emerged as a valuable scaffold in medicinal chemistry owing to its conformational rigidity and favorable three-dimensional architecture. In recent years, 2,5-DBH has been increasingly incorporated into biologically active molecules, functioning as a core unit or structural modulator to improve target engagement and pharmacological profiles. Despite growing interest and scattered reports describing its synthesis and biological evaluation, a unified and systematic assessment of this framework has been lacking. This review critically summarizes recent advances in the synthesis of 2,5-DBH and its derivatives, with particular emphasis on efficient construction strategies, functionalization patterns, and derivatization approaches developed over the past decade. In parallel, the biological applications of 2,5-DBH-based compounds are comprehensively discussed across major therapeutic areas, including oncology, neurological disorders, and antimicrobial research. By integrating synthetic progress with biological insights, this review delineates current trends, identifies key structure–activity relationships, and highlights existing challenges and opportunities. Collectively, this work aims to guide future scaffold design and stimulate further exploration of 2,5-DBH as a versatile platform in drug discovery.