Does the anti-hepatitis B virus activity of (+)-5'-noraristeromycin exist in its 4'-epimer and 4'-deoxygenated derivatives?
To begin an exploration of the structural parameters responsible for the activity of (+)-5'-noraristeromycin toward hepatitis B virus (HBV), three derivatives varied at the C-4' position have been prepared and evaluated. The syntheses began with a Mitsunobu coupling reaction of an appropriate cyclopentanol with 6-chloropurine. The products of these reactions were synthetically altered by standard ammonolysis and deprotection procedures to give the desired products. Evaluation of the new derivatives indicated that removal of the C-4' hydroxyl of (+)-5'-noraristeromycin increased its potency toward HBV by approximately 10-fold.
Seley
K L
KL
Georgetown University Medical Center, Division of Molecular Virology and Immunology, Rockville, Maryland 20852, USA.
Schneller
S W
SW
Korba
B
B
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; C076829:5'-noraristeromycin; D000241:Adenosine