BOA and 6-MBOA (Coixol) Scaffolds: Synthetic Strategies, Potent Bioactive Derivatives, SAR, and Therapeutic Insights

Benzoxazolinone (BOA) and its methoxy analogue, 6-MBOA (Coixol), are privileged heterocyclic scaffolds with diverse pharmacological potential, including neuroprotective, antidiabetic, anti-inflammatory, antimicrobial, and anticancer effects. BOA is a well-studied natural phytoconstituent with broad biological activity, whereas 6-MBOA has received comparatively less attention, despite its emerging biological relevance. The methoxy substitution at the 6-position of 6- MBOA modifies the electronic configuration, enhances lipophilicity, and improves metabolic stability, resulting in superior biological efficacy relative to its parent compound. Among the reported analogues, a benzoxazolinone-based autotaxin inhibitor (compound 26) demonstrated notable potency (IC₅₀;0.019 μM), and several triazole-linked or halogenated derivatives exhibited submicromolar anti-inflammatory and anticancer activities. This review consolidates current knowledge on BOA and 6-MBOA derivatives, focusing on structure-activity relationships, mechanistic underpinnings of bioactivity, and representative synthetic methodologies. Particular attention is given to patented compounds, emphasizing their therapeutic potential and structural innovation. Collectively, these insights establish BOA as a validated pharmacophoric scaffold and highlight 6-MBOA as a promising molecular framework for next-generation drug design and discovery.