From Lab to Target: Pyrazole, Pyrazoline and Fused Pyrazole Derivatives as Receptor Tyrosine Kinase Inhibitors in Cancer Therapy

ABSTRACT Pyrazole derivatives have emerged as versatile scaffolds in the development of receptor tyrosine kinase inhibitors, offering promising avenues for targeted cancer therapy. Their therapeutic potential in cancer therapy is notable in many FDA‐approved anticancer drugs. This review provides a comprehensive overview of the latest research from 2021 regarding novel pyrazole, pyrazoline, and fused pyrazole derivatives targeting receptor tyrosine kinases, namely: AXL, DDR, EGFR, FGFR, MET, CSF1R, RET, and VEGFR‐2. This study focuses on the most active and promising candidates within each series of compounds. Key aspects covered include their cytotoxicity and enzyme inhibition results, with comparisons to reference drugs. The review also covers the molecular docking studies, highlighting critical binding interactions between the compounds and the protein kinase residues, and unveiling their molecular mechanisms of action. Structure–activity relationship analyses are also discussed, revealing the influence of structural modifications on biological activities. Furthermore, synthetic pathways for each series or key compounds are presented, offering a practical guide for researchers in the field. By integrating these elements, this review provides a solid foundation and rationale for the design, synthesis, and optimization of new pyrazole‐based anticancer agents targeting receptor tyrosine kinases.