Thienopyrrolo[2, 3‐d]pyrimidines, New Tricyclic Nucleobase Analogues: Synthesis and Biological Activities.

Abstract: Three isomeric series of 4‐substituted thieno‐fused 7‐deazapurine nucleobases were synthesized by palladium catalyzed couplings or nucleophilic substitutions from protected key‐intermediate 4‐chlorothienopyrrolopyrimidines. Most final nucleobases exerted micromolar activity against hepatitis C virus and respiratory syncytial virus, as well as some in vitro cytostatic activities against several cancer and leukemia cell lines. Three new nucleosides derived from 8H‐thieno[3′, 4′:4,5]pyrrolo[2, 3‐d]pyrimidine were also synthesized and were significantly more cytostatic than corresponding nucleobases, with activities in submicromolar range and low toxicity to normal cycling fibroblasts. [ABSTRACT FROM AUTHOR]