Synthesis and antiviral activity of the enantiomeric forms of carba-5-iodo-2'-deoxyuridine and carba-(E)-5-(2-bromovinyl)-2'-deoxyuridine.
Both enantiomers of the carbocyclic analogues of 5-iodo-2'-deoxyuridine (14 and ent-14) and of (E)-5-(2-bromo-vinyl)-2'-deoxyuridine (16 and ent-16) were synthesized by using (+)- or (-)-endo-norborn-5-en-2-yl acetate or butyrate, respectively, as starting materials. Against herpes simplex virus type 1 (+)-C-BVDU (16) was only slightly less active than BVDU itself, whereas (-)-C-BVDU (ent-16) proved to be 10-400-fold less effective, depending on the strain investigated. Against HSV-2 both (+)- and (-)-C-BVDU as well as (+)- and (-)-C-IDU showed minor activity. All carbocyclic analogues were inactive against TK-HSV-1 strains, pointing to the prerequisite of phosphorylation (activation) by the viral thymidine kinase (TK).
Balzarini
J
J
Institute of Organic Chemistry, Graz University of Technology, Austria.
Baumgartner
H
H
Bodenteich
M
M
De Clercq
E
E
Griengl
H
H
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000494:pharmacology; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D018139:Simplexvirus / Q000187:drug effects; D013237:Stereoisomerism
D000998:Antiviral Agents; D003517:Cyclopentanes; C045200:1-(3-hydroxy-4-(hydroxymethyl)-cyclopentyl)-5-(2-bromovinyl)-2,4-(1H,3H)-pyrimidinedione; C045201:1-(3-hydroxy-4-(hydroxymethyl)cyclopentyl)-5-(2-iodovinyl)-2,4-(1H,3H)-pyrimidinedione; D001973:Bromodeoxyuridine; D003857:Deoxyuridine