Synthetic Strategies and Therapeutic Profile of Some 1,4-benzoxazine Derivatives: A Review

Abstract: Heterocyclic rings containing heteroatoms at the 1,4-position and fused to a benzene ring are essential in medicinal chemistry due to their wide range of therapeutic and biological properties. Among them, 1,4-benzoxazine derivatives are distinguished by their heterocyclic structure, characterized by the fusion of a benzene ring with an oxazine ring with oxygen and nitrogen atoms in 1,4-positions. The latter heterocyclic motif gives these compounds great versatility, improving their chemical stability and promoting specific interactions with various biological targets. These compounds possess various pharmacological properties, including antifungal, antistrophic, antihypertensive, anti-Parkinson, anti- Alzheimer, anti-Huntington, antibacterial, and antirheumatic activities. Various synthetic methods have been developed to obtain 1,4-benzoxazine derivatives. These methods typically involve the condensation of 2-aminophenol with α(β)-dicarbonyl and α-halocarbonyl compounds, alkyl 2- halomalonates, and diethyl fumarate. This review focuses on synthetic approaches and methods used to synthesize 1,4-benzoxazine derivatives. It examines a range of proven pharmacological applications of these derivatives described in the literature from 1960 to 2024. The aim is to provide valuable insights for medicinal and organic chemistry researchers, offering guidance on developing and designing novel 1,4-benzoxazine derivatives.