Hetero-expanded Purine Nucleosides. Design, Synthesis and Preliminary Biological Activity

Abstract

Several thieno-expanded purine nucleoside analogues were synthesized for use as tools in ongoing investigations into nucleic acid structure and function in our laboratories. The inclusion of the thiophene ring system in the nucleoside endows the purine scaffold with advantages not previously available in other reported expanded purines. The synthesis and preliminary biological studies are reported herein.

Antiproliferative activities of halogenated thieno[3,2-d]pyrimidines

“…2). 11,24–27 Notably, several thiophene-expanded purine tricyclic analogues related to those shown in Figure 2, exhibited inhibitory activity against colorectal cancer cell proliferation and trypanosomes. 11,27 As an extension of this early work, the synthesis and biological evaluation of several thiophene ‘extended’ pyrimidine nucleosides was pursued.…”

Synthesis and evaluation of Janus type nucleosides as potential HCV NS5B polymerase inhibitors

“…5,6 IDX-184 1 , RO-5024048/RG-7128 2 , and PSI-7977 (GS-7977) 3 are in advanced clinical trials as effective anti-HCV agents. Interestingly, highly base-modified tricyclic derivatives such as 4 7 and 5 8 have also shown potent anti-HCV activity.…”

Synthesis and biological evaluation of a series of thieno-expanded tricyclic purine 2′-deoxy nucleoside analogues

“…1) has been shown to be a good inhibitor of HCV NS5B polymerase. 27 In the HCV replicon whole cell assay, the ribofuranose thieno-expanded guanosine and adenosine analogues ( 1 and 2 respectively in Fig. 1) possessed moderate inhibitory activity with EC 50 values of 74 and 87 µM, respectively.…”

“…1) possessed moderate inhibitory activity with EC 50 values of 74 and 87 µM, respectively. 27 Another finding was the observation that the nucleoside and nucleobase transporters in Trypanosoma brucei recognized both the ribose analogues in their nucleoside form as well as their corresponding nucleobases. 24 Additionally, the nucleobases of the modified ribonucleosides exhibited interesting cytostatic activity against three cancer cell lines.…”