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

0493609 - ÚOCHB 2019 RIV DE eng J - Journal Article
Tichý, Michal - Smolen, Sabina - Deingruber, Tomáš - Džubák, P. - Pohl, Radek - Poštová Slavětínská, Lenka - Hajdúch, M. - Hocek, Michal
Thienopyrrolo[2, 3-d]pyrimidines, New Tricyclic Nucleobase Analogues: Synthesis and Biological Activities.
ChemistrySelect. Roč. 3, č. 31 (2018), s. 9144-9149. ISSN 2365-6549. E-ISSN 2365-6549
R&D Projects: GA ČR(CZ) GA16-00178S
Grant - others:AV ČR(CZ) AP1501
Program: Akademická prémie - Praemium Academiae
Institutional support: RVO:61388963
Keywords : fused heterocycles * nucleobases * nucleosides * cytostatics * antivirals
OECD category: Organic chemistry
Impact factor: 1.716, year: 2018

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.
Permanent Link: http://hdl.handle.net/11104/0286945