Anti-HBV specific beta-L-2'-deoxynucleosides.
A unique series of simple unnatural L-nucleosides that specifically inhibit hepatitis B virus (HBV) replication has been discovered. These molecules have in common a hydroxyl group in the 3'-position (3'-OH) of the beta-L-2'-deoxyribose sugar that confers antiviral activity specifically against hepadnaviruses. Replacement of the 3'-OH broadens activity to other viruses. Substitution in the base decreases antiviral potency and selectivity. Human DNA polymerases and mitochondrial function are not effected. Plasma viremia is reduced up to 8 logs in a woodchuck model of chronic HBV infection. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.
Bryant
M L
ML
Novirio Pharmaceuticals, Inc., 125 Cambridge Park Dr., Cambridge, Massachussetts 02476, USA. bryant.martin@novirio.com
Bridges
E G
EG
Placidi
L
L
Faraj
A
A
Loi
A G
AG
Pierra
C
C
Dukhan
D
D
Gosselin
G
G
Imbach
J L
JL
Hernandez
B
B
Juodawlkis
A
A
Tennant
B
B
Korba
B
B
Cote
P
P
Cretton-Scott
E
E
Schinazi
R F
RF
Sommadossi
J P
JP
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D003839:Deoxyadenosines / Q000737:chemistry / Q000494:pharmacology; D003841:Deoxycytidine / Q000737:chemistry / Q000494:pharmacology; D003853:Deoxyribonucleosides / Q000737:chemistry / Q000494:pharmacology*; D017919:Hepatitis B Virus, Woodchuck / Q000187:drug effects / Q000502:physiology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy; D006801:Humans; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013936:Thymidine / Q000737:chemistry / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D003839:Deoxyadenosines; D003853:Deoxyribonucleosides; D003841:Deoxycytidine; D013936:Thymidine