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

Four series of some 4-substituted-1-phenyl-1H-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 N1 of pyrimidine or N2 of pyrazole was observed.