Pyridazine and Pyridazinone in Medicinal Chemistry: Synthesis and Antiinflammatory Pathways Targeting TxA2, TNF-α, and IL-6.

Abstract

Inflammation is a fundamental biological reaction to harmful stimuli, which is crucial in the initiation and advancement of different diseases, including rheumatoid arthritis, cardiovascular conditions, neurological disorders such as Alzheimer's and Parkinson's, and multiple cancer types. Chronic inflammation, in particular, contributes to irreversible tissue damage and the progression of disease. Thus, the suppression of key inflammatory mediators has become a promising therapeutic approach. Thromboxane A2 (TxA2), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) are among the mediators that have been thoroughly investigated for their roles in regulating immune responses and sustaining inflammation; therefore, targeting these mediators offers substantial therapeutic potential. In recent years, significant attention has been focused on heterocyclic compounds, especially pyridazine and pyridazinone derivatives, owing to their structural diversity and extensive biological activity. These scaffolds have shown significant effectiveness in regulating inflammatory pathways by limiting TxA2 production, reducing TNF-α release, and disrupting IL-6 signaling. This review presents a comprehensive overview of pyridazine and pyridazinone-based compounds as potential anti-inflammatory agents. It highlights both traditional and current synthetic strategies used in their development and explores their mechanisms of action with respect to key inflammatory targets. Additionally, the study examines recent pharmacological assessments and preclinical results, offering insights into the medicinal uses of these substances. A brief perspective on future research directions is also included, emphasizing the need for further structural optimization, in vivo validation, and clinical translation. Collectively, these results highlight the potential of pyridazine and pyridazinone derivatives in the development of advanced anti-inflammatory pharmaceuticals.