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

Abstract

Pyrazole and its derivatives remain popular heterocycles in drug design, and development. Pyrazole derivatives been extensively studied by the scientific community and as they possess a wide range of biological activity, especially anti‐EGFR properies. Overexpression of EGFR signaling promotes tumor growth by inhibiting apoptosis. EGFR dysfunction has been described in several cancer. Therefore, EGFR represents a prospective target for cancer treatment. Several anti‐EGFR drugs are thriving the market, notably dacomitinib, afatinib, erlotinib etc. However, almost all drugs have limited therapeutic effectiveness due to a lack of selectivity as well as substantial side effects. To address this, innovative therapeutic anti‐EGFR drugs with high effectiveness and low toxicity are needed. To combat therapeutic resistance to EGFR inhibitors, pyrazole, and pyrazole‐based derivatives have been explored as a promising pharmacophore for developing novel compounds with higher potency, lower toxicity, and desirable pharmacokinetic profiles. The current review outlines the investigation of advancements towards anti‐ EGFR via pyrazole, pyrazoline, and fused pyrazole‐based compounds and represents inclusive data on pyrazole‐based marketed drugs as well as therapeutic candidates undergoing preclinical and clinical development. We have also summarised structure‐activity relationship (SAR), mechanistic studies to afford ideas for the design and development of new anti‐EGFR derivatives.