Cytostatic 6-arylpurine nucleosides. 6. SAR in anti-HCV and cytostatic activity of extended series of 6-hetarylpurine ribonucleosides.
Significant anti-HCV activity of 6-hetarylpurine ribonucleosides has been discovered and is reported here for the first time and compared with cytostatic effect. An extended series of 6-hetarylpurine nucleosides has been prepared by heterocyclizations in position 6 of purine nucleosides or by cross-couplings of 6-chloropurine nucleosides with hetarylboronic acids, -stannanes, or -zinc halides. The most anti-HCV active were purine ribonucleosides bearing pyrrol-3-yl or 2-furyl groups exerting EC(90) = 0.14 and 0.4 microM, respectively.
Hocek
Michal
M
Centre for New Antivirals and Antineoplastics, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, CZ-16610 Prague 6, Czech Republic. hocek@uochb.cas.cz
Naus
Petr
P
Pohl
Radek
R
Votruba
Ivan
I
Furman
Phillip A
PA
Tharnish
Phillip M
PM
Otto
Michael J
MJ
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; D004354:Drug Screening Assays, Antitumor; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D051379:Mice; 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