Cytostatic and antiviral 6-arylpurine ribonucleosides. Part 7: synthesis and evaluation of 6-substituted purine l-ribonucleosides.
A series of purine l-ribonucleosides 2a-2i bearing diverse C-substituents (alkyl, aryl, hetaryl or hydroxymethyl) in the position 6 were prepared by Pd-catalyzed cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-beta-l-ribofuranosyl)purine with the corresponding organometallics followed by deprotection. Unlike their d-ribonucleoside enantiomers that possess strong cytostatic and anti-HCV activity, the l-ribonucleosides were inactive except for 6-benzylpurine nucleoside 2h showing moderate anti-HCV effect in replicon assay. A triphosphate of 2h did not inhibit HCV RNA polymerase.
Hocek
Michal
M
Gilead Sciences & IOCB Research Center, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic. hocek@uochb.cas.cz
Silhár
Peter
P
Shih
I-hung
IH
Mabery
Eric
E
Mackman
Richard
R
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006367:HeLa Cells; D016174:Hepacivirus / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D011684:Purine Nucleosides; D012263:Ribonucleosides