Synthesis of methylene-bridged analogues of biologically active pteridine derivatives

The hepatitis C virus (HCV) is a major cause of liver disease worldwide. The HCV NS5B RNA-dependent RNA polymerase, which is a central enzyme in the replication of the virus, has become a potential target for design and synthesis of small molecule inhibitors useful in the treatment of HCV infection by interfering with viral replication. In this publication we describe the synthesis of cyclic analogues of biologically active pteridine derivatives of type B. The key step in the formation of target compounds 1-8, is the condensation reaction of tricyclic diketones 10 and 11 with commercially available 4,5-diamino-6-hydroxypyrimidine (9). Subsequent chlorination and amination reactions led to the formation of the target molecules 1-8, which were further biologically evaluated. ((c) Wiley-VCH Verlag GmbH & Co.