Pyrazinone Derivatives in Medicinal Chemistry: SAR Insights and Emerging Therapeutic Applications. (PubMed, Med Chem) - Sep 22, 2026 - "Clinically relevant examples, including the antiviral drug favipiravir and the clinical-stage candidates RWJ-671818 and BI 730357, nonetheless demonstrate that this bottleneck is surmountable and illustrate the scaffold's translational potential. Recent advances, emerging resistance mechanisms, and future directions, including multi-target-directed ligand design, structure-based optimization, and AI-assisted drug design, are also discussed. By consolidating this fragmented literature into a single cross-scaffold structure-activity framework and by pinpointing where pharmacokinetic and toxicological characterization, rather than potency optimization, most limits clinical translation, this review provides a practical, decisionoriented resource for researchers designing the next generation of pyrazinone-based therapeutics."
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Neetu Agrawal; Priya Kushwah; Shilpi Pathak
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