Chapter I. Synthesis, modification and bioactivity of bicyclic thieno[3,2-D]pyrimidines

Thieno(3,2-d)pyrimidine as a component of the nucleobase scaffold

During the course of the investigation, key intermediates, including the heterocyclic bases, were subjected to broad screen biological testing. Although the original purpose was to explore the biological properties of the nucleosides, the halogenated thieno[3,2-d]pyrimidine intermediates1and2were found to exhibit antiproliferative properties against several cancer cell lines. Furthermore, the cell cycle and apoptosis studies revealed their ability to induce apoptosis independent of cell cycle. In addition, evaluations of their antimicrobial activity lead to selective inhibition of clinical strains of Cryptococcus neoformans. Since A and B are reaction intermediates, their syntheses had been reported previously, however a search of the literature revealed that surprisingly, there were no reports of biological activity, including against cancer. Herein we describe a structure activity relationship study for a series of thieno[3,2-d]pyrimidine analogues that facilitated identification of core functional groups responsible for their biological activity[72].