Pyrazole, Pyrazoline, and Fused Pyrazole Derivatives: New Horizons in EGFR‐Targeted Anticancer Agents

Abstract

AbstractPyrazole and its derivatives remain popular heterocycles in drug research, design, and development. Several drugs include the pyrazole scaffold, such as ramifenazone, ibipinabant, antipyrine, and axitinib, etc. They have been extensively studied by the scientific community and are said to have a wide range of biological activity, especially anticancer agents targeting EGFR. Overexpression of EGFR signalling promotes tumor growth by inhibiting apoptosis. EGFR dysfunction has been described in multiple cancers, including colon, head and neck, NSCLC, colon, liver, breast, and ovarian cancer. As a result, EGFR represents a prospective target for cancer treatment. Several anti‐EGFR drugs are thriving, notably dacomitinib, afatinib, erlotinib, gefitinib, and osimertinib. However, almost all currently available anti‐EGFR drugs have limited therapeutic effectiveness due to a lack of selectivity as well as substantial side effects. Furthermore, aberrant EGFR signalling across numerous human malignancies/carcinomas is impeded by gene amplification, protein overexpression, mutations, or in‐frame deletions, making EGFR‐induced cancer treatment challenging. To overcome such, novel therapeutic anti‐EGFR drugs with high efficacy and minimal toxicity are required. To battle cancer and therapeutic resistance to EGFR inhibitors, pyrazole, pyrazoline, and their derivatives have been investigated as a viable pharmacophore for the development of new drugs with better potency, lesser toxicity, and favourable pharmacokinetic characteristics. The present investigation covers the examination of progress toward anti‐cancer therapies targeting EGFR via pyrazole, pyrazoline, and fused pyrazole‐based compounds. The current study also represents inclusive data on pyrazole‐based marketed drugs as well as therapeutic candidates undergoing preclinical and clinical development. Lastly, we have discussed recent advances in the medicinal chemistry of pyrazole‐based derivatives with their anti‐EGFR significance for the eradication of various cancers and provide the direction toward structure‐activity relationship (SAR), including mechanistic studies.