ABSTRACT
<p><b>OBJECTIVE</b>To build 3D-pharmacophore model of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors using distance comparisons method and design novel EGFR inhibitors.</p><p><b>METHODS</b>Thirteen typical EGFR inhibitors were selected, and their biologically active conformations were obtained by using DOCK5.0 program, then 3D-pharmacophore model of EGFR inhibitors was built using distance comparisons method.</p><p><b>RESULTS</b>Validation of the 3D-pharmacophore model was carried out and novel structures with potential inhibitory activity were selected by means of 3D-searching and docking method.</p><p><b>CONCLUSION</b>This method can improve hit rate of lead compounds discovery and can be used to design novel EGFR inhibitors.</p>
Subject(s)
Drug Design , Enzyme Inhibitors , Epidermal Growth Factor , Metabolism , Models, Chemical , Protein-Tyrosine Kinases , Chemistry , Pharmacology , ErbB Receptors , Chemistry , Structure-Activity RelationshipABSTRACT
<p><b>AIM</b>Design, synthesis and evaluation of a series of 7-imidazolylalkanamido-1-carboxylalkylbenzodiazepine farnesyltransferase (FTase) inhibitors.</p><p><b>METHODS AND RESULTS</b>Coupling of imidazolylalkylcarboxylic acids and 1-substituted 7-aminobenzodiazepines (5a-5c) yielded 10 new compounds (6-12, 16-18) which were biologically tested against FTase using scintillation proximity assay method.</p><p><b>CONCLUSION</b>Five target compounds were found to be potential farnesyltransferase inhibitors.</p>