ABSTRACT
A microwave-assisted solid-phase synthesis of heteroannulated 1,3-oxazin-6-ones has been developed. Significant rate enhancement was observed for all steps carried out under microwave irradiation, and the overall reaction time was dramatically shortened when compared to the conventional procedures. A representative set of 20 bi- and tricyclic heteroannulated 1,3-oxazin-6-ones was prepared. Key steps in the synthesis are (i) five-member heterocycle formation, (ii) acylation of amine, and (iii) ring closure to give the heteroannulated 1,3-oxazin-6-one.
Subject(s)
Combinatorial Chemistry Techniques/methods , Oxazines/chemical synthesis , Acylation , Amines/chemical synthesis , Amines/chemistry , Combinatorial Chemistry Techniques/economics , Cyclization , Microwaves , Molecular Structure , Oxazines/chemistry , Time FactorsABSTRACT
The traceless solid-phase syntheses of 6-oxopurines and pyrazolo[3,4-d]pyrimidines are presented. The effects of these compounds on multidrug resistance protein 4 (MRP4/ABCC4) facilitated efflux was examined. Four of the compounds, 7b, 7c, 15a, and 17e, were active in inhibiting MRP4-mediated efflux of the bimane-glutathione conjugate. In addition, all four compounds were also able to reverse MRP4-mediated resistance to the anticancer drug 6-thioguanine. In the presence of 25 microM 15a or 17e, there was complete reversal. The reversal of resistance was achieved without any effects on the uptake and metabolism of 6-thioguanine.
