Cell cycle experiments with our previously reported 4-biphenylaminoquinazolines (1-3) multi-tyrosine 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. While 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.

Discovery Of Biarylaminoquinazolines As Novel Tubulin Polymerization Inhibitors

MARZARO, GIOVANNI;FERRARESE, ALESSANDRO;BRUN, PAOLA;CASTAGLIUOLO, IGNAZIO;CONCONI, MARIA TERESA;CHILIN, ADRIANA
2014

Abstract

Cell cycle experiments with our previously reported 4-biphenylaminoquinazolines (1-3) multi-tyrosine 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. While 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/3018505
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