Synthesis and Cytostatic and Antiviral Profiling of Thieno-Fused 7-Deazapurine Ribonucleosides

0475217 - ÚOCHB 2018 RIV US eng J - Článek v odborném periodiku
Tichý, Michal - Smolen, Sabina - Tloušťová, Eva - Pohl, Radek - Oždian, T. - Hejtmánková, K. - Lišková, B. - Gurská, S. - Džubák, P. - Hajdúch, M. - Hocek, Michal
Synthesis and Cytostatic and Antiviral Profiling of Thieno-Fused 7-Deazapurine Ribonucleosides.
Journal of Medicinal Chemistry. Roč. 60, č. 6 (2017), s. 2411-2424. ISSN 0022-2623. E-ISSN 1520-4804
Grant CEP: GA ČR(CZ) GA16-00178S; GA TA ČR(CZ) TE01020028; GA MŠMT(CZ) LO1304
Institucionální podpora: RVO:61388963
Klíčová slova: adenosine kinase inhibitors * cross-coupling reactions * cytotoxic nucleoside analogs
Obor OECD: Organic chemistry
Impakt faktor: 6.253, rok: 2017
http://pubs.acs.org/doi/full/10.1021/acs.jmedchem.6b01766

Two isomeric series of new thieno-fused 7-deazapurine ribonucleosides (derived from 4-substituted thieno[2',3':4,5]pyrrolo[2,3-d]pyrimidines and thieno-[3',2':4,5]pyrrolo[2,3-d]pyrimidines) were synthesized by a sequence involving Negishi coupling of 4,6-dichloropyrimidine with iodothiophenes, nucleophilic azidation, and cyclization of tetrazolopyrimidines, followed by glycosylation and cross-couplings or nucleophilic substitutions at position 4. Most nucleosides (from both isomeric series) exerted low micromolar or submicromolar in vitro cytostatic activities against a broad panel of cancer and leukemia cell lines and some antiviral activity against HCV. The most active were the 6-methoxy, 6-methylsulfanyl, and 6-methyl derivatives, which were highly active to cancer cells and less toxic or nontoxic to fibroblasts.
Trvalý link: http://hdl.handle.net/11104/0272060