Synthesis, cytostatic and anti-HCV activity of 6-(N-substituted aminomethyl)-, 6-(O-substituted hydroxymethyl)- and 6-(S-substituted sulfanylmethyl)purine nucleosides.
An efficient and facile synthesis of a large series of diverse 6-(N-substituted aminomethyl)-, 6-(O-substituted hydroxymethyl)- and 6-(S-substituted sulfanylmethyl)purine nucleosides (55 examples of both ribo- and 2'-deoxyribonucleosides), aimed at identifying novel homologues of natural nucleosides, was developed. The key transformation involved nucleophilic substitutions of Tol-protected 6-(mesyloxymethyl)purine nucleosides by primary or secondary amines, alcoholates or thiolates. While the 2'-deoxyribonucleosides were inactive, the ribonucleosides exerted considerable cytostatic effects and some anti-HCV activity with low selectivity.
Silhár
Peter
P
Institute of Organic Chemistry and Biochemistry, v.v.i., Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
Hocek
Michal
M
Pohl
Radek
R
Votruba
Ivan
I
Shih
I-Hung
IH
Mabery
Eric
E
Mackman
Richard
R
D000586:Amination; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D006900:Hydroxylation; D008698:Mesylates / Q000737:chemistry; D008745:Methylation; D051379:Mice; D015394:Molecular Structure; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013457:Sulfur Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000998:Antiviral Agents; D054697:Cytostatic Agents; D008698:Mesylates; D011684:Purine Nucleosides; D013457:Sulfur Compounds