Cell 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.
Discovery of biarylaminoquinazolines as novel tubulin polymerization inhibitors / Marzaro, G.; Coluccia, Antonio; Ferrarese, A.; Brun, P.; Castagliuolo, I.; Conconi, M. T.; LA REGINA, Giuseppe; Bai, R.; Silvestri, Romano; Hamel, E.; Chilin, A.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 57:(2014), pp. 4598-4605. [10.1021/jm500034j]
Discovery of biarylaminoquinazolines as novel tubulin polymerization inhibitors
COLUCCIA, Antonio;LA REGINA, GIUSEPPE;SILVESTRI, Romano;
2014
Abstract
Cell 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
