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Synthesis of Water Soluble Bis‐triazenoquinazolines: An Unusual Predicted Mode of Binding to the Epidermal Growth Factor Receptor Tyrosine Kinase
Author(s) -
Larroque AnneLaure,
Peori Brad,
Williams Christopher,
Fang You Qiang,
Qiu Qiyu,
Rachid Zakaria,
JeanClaude Bertrand J.
Publication year - 2008
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2008.00638.x
Subject(s) - moiety , linker , tyrosine kinase , epidermal growth factor receptor , chemistry , tyrosine , stereochemistry , receptor tyrosine kinase , ring (chemistry) , binding site , molecular model , growth factor receptor , molecule , biophysics , epidermal growth factor , autophosphorylation , receptor , biochemistry , kinase , biology , protein kinase a , organic chemistry , computer science , operating system
A novel type of 3,3‐disubstituted bis‐triazenes containing an ethylaminoethyl linker flanked by two identical anilinoquinazoline ring was synthesized. These model molecules contained an N ‐ethylaminomorpholine moiety designed to enhance water solubility. Despite their significant bulkiness, they blocked epidermal growth factor receptor (EGFR) tyrosine kinase in a dose‐dependent manner with IC 50 values in low micromolar range. Molecular modeling to predict the interactions of the molecule with the ATP binding site of EGFR suggests that the N ‐ethylaminomorpholine side chain plays a binding role.