The 4',4'-difluoro analog of 5'-noraristeromycin: a new structural prototype for possible antiviral drug development toward orthopoxvirus and cytomegalovirus.
As a surrogate for 4'-hydroxy-5'-noraristeromycin and related carbocyclic nucleosides, an efficient, enantiodivergent synthetic route to both enantiomers of 5-(6-amino-9H-purin-9-yl)-3,3-difluorocyclopentane-1,2-diol (6 and ent-6) has been developed from a common starting material ((+)-(1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate, 10). Both compounds were assayed versus a series of viruses. The only response found was for compound 6 toward vaccinia and cowpox (EC50 of 143 and 94 microM, respectively) and human cytomegalovirus (EC50 of 6.2 microM). Both compounds were non-cytotoxic. While not as active as cidofovir toward the orthopox viruses and ganciclovir toward cytomegalovirus, compound 6 offers a new structural prototype upon which to build for uncovering new agents effective against these viral types.
Roy
Atanu
A
Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA.
Schneller
Stewart W
SW
Keith
Kathy A
KA
Hartline
Caroll B
CB
Kern
Earl R
ER
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D018155:Orthopoxvirus / Q000187:drug effects* / Q000254:growth & development; D014709:Vero Cells; D010948:Viral Plaque Assay
D000998:Antiviral Agents; C076829:5'-noraristeromycin; D000241:Adenosine