Discovery of biarylaminoquinazolines as novel tubulin polymerization inhibitors.

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.

SUBMITTER: Marzaro G 

PROVIDER: S-EPMC4086859 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature