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

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2017-03, Vol.60 (6), p.2411-2424
Main Authors: Tichý, Michal, Smoleń, Sabina, Tloušt’ová, Eva, Pohl, Radek, Oždian, Tomáš, Hejtmánková, Klára, Lišková, Barbora, Gurská, Soňa, Džubák, Petr, Hajdúch, Marián, Hocek, Michal
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antiviral Agents - chemical synthesis
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Cell Line, Tumor
Hepacivirus - drug effects
Hepatitis C - drug therapy
Humans
Neoplasms - drug therapy
Purines - chemical synthesis
Purines - chemistry
Purines - pharmacology
Ribonucleosides - chemical synthesis
Ribonucleosides - chemistry
Ribonucleosides - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.6b01766