An epimer of 5'-noraristeromycin and its antiviral properties.
A derivative of 5'-noraristeromycin epimeric at the 5'-nor center ((-)-3) has been prepared enantiospecifically in three steps from (+)-((1R,4S)-4-hydroxy-2-cyclopenten- 1-yl acetate. Compound (-)-3 was evaluated for antiviral activity against a large number of viruses and found to display marked activity against varicella-zoster virus, vaccinia virus, vesicular stomatitis virus, parainfluenza virus, reovirus, and cytomegalovirus. A similar antiviral activity spectrum was shown by the S-adenosylhomocysteine hydrolase inhibitors neplanocin A and carbocyclic 3-deazaadenosine. While equally potent as neplanocin A against most of the viruses tested, compound (-)-3 was significantly less cytotoxic. The results of this study suggest that (-)-3 should be pursued for the treatment of those virus infections [that is, pox (VV), rhabdo (VSV), paramyxo (parainfluenza), and reo] that appear to be exquisitively sensitive to the compound.
Siddiqi
S M
SM
Department of Chemistry, University of South Florida, Tampa 33620-5250.
Chen
X
X
Schneller
S W
SW
Ikeda
S
S
Snoeck
R
R
Andrei
G
G
Balzarini
J
J
De Clercq
E
E
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D043383:Adenosylhomocysteinase; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D004285:Dogs; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014780:Viruses / Q000187:drug effects
D000998:Antiviral Agents; C076829:5'-noraristeromycin; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine