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Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

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...

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Autores principales: Perlíková, Pavla, Hocek, Michal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656927/
https://www.ncbi.nlm.nih.gov/pubmed/28834581
http://dx.doi.org/10.1002/med.21465
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author Perlíková, Pavla
Hocek, Michal
author_facet Perlíková, Pavla
Hocek, Michal
author_sort Perlíková, Pavla
collection PubMed
description 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.
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spelling pubmed-56569272017-11-01 Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides Perlíková, Pavla Hocek, Michal Med Res Rev Review Articles 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. John Wiley and Sons Inc. 2017-08-23 2017-11 /pmc/articles/PMC5656927/ /pubmed/28834581 http://dx.doi.org/10.1002/med.21465 Text en © 2017 The Authors Medicinal Research Reviews Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Articles
Perlíková, Pavla
Hocek, Michal
Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides
title Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides
title_full Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides
title_fullStr Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides
title_full_unstemmed Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides
title_short Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides
title_sort pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656927/
https://www.ncbi.nlm.nih.gov/pubmed/28834581
http://dx.doi.org/10.1002/med.21465
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