Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides
Open Access
- 23 August 2017
- journal article
- review article
- Published by Wiley in Medicinal Research Reviews
- Vol. 37 (6), 1429-1460
- https://doi.org/10.1002/med.21465
Abstract
7‐Deazapurine (pyrrolo[2,3‐d]pyrimidine) nucleosides are important analogues of biogenic purine nucleosides with diverse biological activities. Replacement of the N7 atom with a carbon atom makes the five‐membered ring more electron rich and brings a possibility of attaching additional substituents at the C7 position. This often leads to derivatives with increased base‐pairing in DNA or RNA or better binding to enzymes. Several types of 7‐deazapurine nucleosides with potent cytostatic or cytotoxic effects have been identified. The most promising are 7‐hetaryl‐7‐deazaadenosines, which are activated in cancer cells by phosphorylation and get incorporated both to RNA (causing inhibition of proteosynthesis) and to DNA (causing DNA damage). Mechanism of action of other types of cytostatic nucleosides, 6‐hetaryl‐7‐deazapurine and thieno‐fused deazapurine ribonucleosides, is not yet known. Many 7‐deazaadenosine derivatives are potent inhibitors of adenosine kinases. Many types of sugar‐modified derivatives of 7‐deazapurine nucleosides are also strong antivirals. Most important are 2′‐C‐methylribo‐ or 2′‐C‐methyl‐2′‐fluororibonucleosides with anti‐HCV activities (several compounds underwent clinical trials). Some underexplored areas of potential interest are also outlined.Keywords
Funding Information
- Grantová Agentura České Republiky (16-0011785)
- Akademie Věd České Republiky (Praemium Academiae)
This publication has 163 references indexed in Scilit:
- Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicingBlood Cancer Journal, 2012
- Synthesis and antiviral activity of 2′-deoxy-2′-fluoro-2′-C-methyl-7-deazapurine nucleosides, their phosphoramidate prodrugs and 5′-triphosphatesBioorganic & Medicinal Chemistry Letters, 2011
- Ibulocydine Is a Novel Prodrug Cdk Inhibitor That Effectively Induces Apoptosis in Hepatocellular Carcinoma CellsJournal of Biological Chemistry, 2011
- Sustained Viral Response in a Hepatitis C Virus-Infected Chimpanzee via a Combination of Direct-Acting Antiviral AgentsAntimicrobial Agents and Chemotherapy, 2011
- Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue VirusesJournal of Medicinal Chemistry, 2010
- Inhibition of Dengue Virus by an Ester Prodrug of an Adenosine AnalogAntimicrobial Agents and Chemotherapy, 2010
- Inhibition of Dengue Virus RNA Synthesis by an Adenosine NucleosideAntimicrobial Agents and Chemotherapy, 2010
- An adenosine nucleoside inhibitor of dengue virusProceedings of the National Academy of Sciences, 2009
- Robust Antiviral Efficacy upon Administration of a Nucleoside Analog to Hepatitis C Virus-Infected ChimpanzeesAntimicrobial Agents and Chemotherapy, 2009
- Synthesis and Anti-Hepatitis B Virus and Anti-Hepatitis C Virus Activities of 7-Deazaneplanocin A Analogues in VitroJournal of Medicinal Chemistry, 2008