jm500034j_si_001.pdf (739.82 kB)
Discovery of Biarylaminoquinazolines as Novel Tubulin Polymerization Inhibitors
journal contribution
posted on 2014-06-12, 00:00 authored by Giovanni Marzaro, Antonio Coluccia, Alessandro Ferrarese, Paola Brun, Ignazio Castagliuolo, Maria Teresa Conconi, Giuseppe La Regina, Ruoli Bai, Romano Silvestri, Ernest Hamel, Adriana ChilinCell cycle experiments with our previously
reported 4-biphenylaminoquinazoline
(1–3) multityrosine kinase inhibitors
revealed an activity profile resembling that of known tubulin polymerization
inhibitors. Novel 4-biarylaminoquinazoline analogues of compound 2 were synthesized and evaluated as inhibitors of several
tyrosine kinases and of tubulin. Although compounds 1–3 acted as dual inhibitors, the heterobiaryl
analogues possessed only anti-tubulin properties and targeted the
colchicine site. Furthermore, molecular modeling studies allowed the
rationalization of the pharmacodynamic properties of the compounds.