ABSTRACT
A series of C-6 or C-3' alkynyl-substituted 4-anilinoquinazoline derivatives was prepared straightforwardly by a Sonogashira reaction of the corresponding bromo-substituted 4-anilinoquinazolines. Bioactive assay of these compounds for in vitro EGFR kinase inhibition demonstrated that the novel 6-hydroxypropynyl-4-anilinoquinazoline 5e was a very potent EGFR kinase inhibitor with an IC(50) of 14 nM.
Subject(s)
Aniline Compounds/chemical synthesis , Aniline Compounds/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , ErbB Receptors/antagonists & inhibitors , Quinazolines/chemical synthesis , Quinazolines/pharmacology , Aniline Compounds/chemistry , Antineoplastic Agents/chemistry , Computer Simulation , Drug Screening Assays, Antitumor , Inhibitory Concentration 50 , Models, Molecular , Molecular Structure , Quinazolines/chemistry , Structure-Activity RelationshipABSTRACT
N-Substituted isatin derivatives were prepared from the reaction of isatin and various bromides via two steps. Bioactivity assay results (in vitro tests) demonstrated that some of these compounds are potent and selective inhibitors against SARS coronavirus 3CL protease with IC50 values ranging from 0.95 to 17.50 microM. Additionally, isatin 4o exhibited more potent inhibition for SARS coronavirus protease than for other proteases including papain, chymotrypsin, and trypsin.
