4‐Substituted‐1‐phenyl‐1 H ‐pyrazolo[3,4‐ d ]pyrimidine Derivatives: Design, Synthesis, Antitumor and EGFR Tyrosine Kinase Inhibitory Activity

Four series of some 4‐substituted‐1‐phenyl‐1 H ‐pyrazolo[3,4‐ d ]pyrimidine derivatives 5a – f , 6a – f , 8a – f , and 9a – f were designed to be screened for their antitumor activity. All compounds were evaluated against breast ( MCF ‐7) and lung ( A ‐549) cell lines. Six compounds 5a , 5b , 6b , 6e , 9e , and 9f displaying activity against both cell lines were further estimated for their EGFR ‐ TK inhibitory activity where they revealed 41–91% inhibition and compound 6b elicited the highest activity (91%). A docking study of these compounds into the ATP ‐binding site of EGFR ‐ TK demonstrated their binding mode where H ‐bonding interaction with Met793 through N 1 of pyrimidine or N 2 of pyrazole was observed.