학술논문
4-Substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine Derivatives: Design, Synthesis, Antitumor and EGFR Tyrosine Kinase Inhibitory Activity
Document Type
Academic Journal
Source
Chemical Biology and Drug Design. May 01, 2015 85(5):608-622
Subject
Language
English
ISSN
1747-0277
Abstract
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 N of pyrimidine or N of pyrazole was observed. : Four series of compounds comprising the pyrazolo[3,4-d]pyrimidine core substituted at position 4 with various heterocyclic substitutions were synthesized. Antitumor activity and EGFR-TK inhibition were evaluated.(Figure is included in full-text article.)