Document Detail


Synthesis and biological evaluation of 6-(alkyn-1-yl)furo[2,3-d]pyrimidin-2(3H)-one base and nucleoside derivatives.
MedLine Citation:
PMID:  16392824     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Derivatives of the 2'-deoxynucleoside of furo[2,3-d]pyrimidin-2(3H)-one with long-chain alkyl (or 4-alkylphenyl) substituents at C6 exhibit remarkable anti-VZV (varicella-zoster virus) potency and selectivity, and analogous 2',3'-dideoxynucleoside derivatives show anti-HCMV (human cytomegalovirus) activity. We now report a synthetic approach that enables the preparation of long-chain 6-(alkyn-1-yl)furo[2,3-d]pyrimidin-2(3H)-ones in which the rodlike acetylene spacer replaces the 4-substituted-phenyl ring at C6. Analogues with methyl, beta-d-ribofuranosyl, beta-d-arabinofuranosyl, and 2-deoxy-beta-d-erythro-pentofuranosyl substituents at N3 have been prepared. Long-chain derivatives at C6 in the 2'-deoxynucleoside series showed virus-encoded nucleoside kinase-sensitive anti-VZV activity. Surprisingly, 3-methyl-6-(octyn-1-yl)furo[2,3-d]pyrimidin-2(3H)-one (prepared as a negative anti-VZV test control) exhibited anti-HCMV activity, which supports the possibility of development of non-nucleoside anti-HCMV agents originating from uncomplicated derivatives of such bicyclic ring systems.
Authors:
Morris J Robins; Karl Miranda; Vivek K Rajwanshi; Matt A Peterson; Graciela Andrei; Robert Snoeck; Erik De Clercq; Jan Balzarini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  49     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-05     Completed Date:  2006-02-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  391-8     Citation Subset:  IM    
Affiliation:
Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602-5700, USA. morris_robins@byu.edu
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MeSH Terms
Descriptor/Qualifier:
Antiviral Agents / chemical synthesis*,  chemistry,  pharmacology*
Cell Line
Cell Proliferation / drug effects
Cytomegalovirus / drug effects
Herpesvirus 3, Human / drug effects
Humans
Microbial Sensitivity Tests
Molecular Structure
Pyrimidine Nucleosides / chemical synthesis*,  chemistry,  pharmacology*
Stereoisomerism
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Antiviral Agents; 0/Pyrimidine Nucleosides

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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