New Quinazoline Derivatives Synthesis And Biological Activity Study

In order to create novel and high antifungal and antiviral agents,two new series of quinazoline derivatives were designed and synthesized.Eleven new 6-bromo-4-alkylthio quinazoline derivatives(â… a～k) and four 4-[4'-(α-aminophosphonates-)]-yloxyphenyl-quinazoline derivatives(â…¡a～d) were synthesized.The structures of the new compounds were verified by IR,¹H NMR,¹³C NMR and elemental analyses.The synthetic condition for the intermediates and target compounds were optimized. 6-Bromo-4-alkylthio-quinazoline derivatives were synthesized using tetrabutylammoni-umbromide (TBAB) as phase transfer catalyst with acetonitrile as solvent and yield was increased more than 20%under the optimized reactant conditions.This condition is far more effective than the conventional method for solid halohydrocarbons.For the second series of compounds,the most important intermediate 4-chloroquinazoline was prepared by phosphorus oxychloride together with triethylamine.And this conditions gave much higher yield(75%) in shorter reaction time(2 h) than the conventional technique(yield 55%and reaction time 18～20 h).The preliminary biological activity test showed that these two series derivatives displayed certain antifungal activity against three kinds of fungi in vitro,however with a degree of variation.At 50μg/mL,the antifungal activity of Ig against Gibberella zeae,Cytospora mandshurica and Fusarium oxysporum are 63.8%,51.9%, 55.1%respectively which are similar to that of the commercial agent Hymexazol.The results showed that most of our designed compounds had moderate antiviral activities at 500 mg/L against TMV in vivo.