Structure-Activity Relationship Studies Based on Quinazoline Derivatives as EGFR Kinase Inhibitors (2017-Present)

Area of Science:

• Oncology
• Medicinal Chemistry
• Pharmacology

Background:

• Epidermal growth factor receptor (EGFR) is crucial in cancer development.
• Targeting mutant EGFR with inhibitors is a key therapeutic strategy.
• Quinazoline derivatives show high affinity for EGFR kinase active sites.

Purpose of the Study:

• To review structural modifications enhancing EGFR inhibitory activity.
• To cover common (del19, L858R) and resistance (T790M, C797S) EGFR mutants.
• To overview novel quinazoline derivatives as potential EGFR inhibitors.

Main Methods:

• Literature review of quinazoline-based EGFR inhibitors.
• Analysis of structure-activity relationships for EGFR inhibition.
• Survey of newly synthesized quinazoline derivatives.

Main Results:

• Five first-generation and two second-generation quinazoline EGFR inhibitors are approved.
• Specific structural modulations improve affinity for mutant EGFR forms.
• Novel quinazoline derivatives exhibit potential as competitive, covalent, or allosteric inhibitors.

Conclusions:

• Quinazoline scaffolds are highly effective for developing EGFR inhibitors.
• Understanding structural requirements is key to overcoming resistance mutations.
• New quinazoline derivatives offer promising therapeutic avenues for EGFR-driven cancers.