cis-trans-isomerization of [E]-5-(2-bromovinyl)-2,2'-anhydrouridine in vivo in rats.
1. [E]-5-(2-bromovinyl)-2,2'-anhydrouridine [( E]BVANUR) has considerable antiviral activity against herpes simplex virus type 1 (HSV-1). 2. [E]BVANUR is not a substrate of pyrimidine nucleoside phosphorylases, but it is an inhibitor of uridine phosphorylase (Ki = 450 nM). 3. [E]BVANUR (trans-isomer, parent compound) undergoes isomerization to [Z]BVANUR (cis-isomer), the only metabolite in rat, which was identified by h.p.l.c., mass spectra and n.m.r. spectroscopy. 4. Absorption of the drug from the gastrointestinal tract after oral administration is minimal. Absorption of [E]BVANUR from the abdominal cavity after i.p. administration was slow.
Szinai
I
I
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
Veres
Z
Z
Szabolcs
A
A
Gács-Baitz
E
E
Ujszászy
K
K
Dénes
G
G
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D001345:Autoradiography; D001711:Biotransformation; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains; D018139:Simplexvirus / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution; D014529:Uridine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D014753:Vinyl Compounds / Q000493:pharmacokinetics / Q000494:pharmacology
D000998:Antiviral Agents; D014753:Vinyl Compounds; C070087:5-(2-bromovinyl)-2,2'-anhydrouridine; C020235:brivudine; D001973:Bromodeoxyuridine; D014529:Uridine