Synthesis and antiviral activity of the carbocyclic analogues of (E)-5-(2-halovinyl)-2'-deoxyuridines and (E)-5-(2-halovinyl)-2'-deoxycytidines.
The carbocyclic analogues of the potent and selective antiherpes agents (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU), and (E)-5-(2-bromovinyl)-2'-deoxycytidine (BVDC) were synthesized by conventional methods with use of carbocyclic 2'-deoxyuridine as starting material. C-BVDU, C-IVDU, and C-BVDC were equally selective, albeit slightly less potent, in their antiherpes action than BVDU, IVDU, and BVDC. Although resistant to degradation by pyrimidine nucleoside phosphorylases, C-BVDU did not prove more effective than BVDU in the systemic (oral, intraperitoneal) or topical treatment of HSV-1 infections in mice.
Herdewijn
P
P
De Clercq
E
E
Balzarini
J
J
Vanderhaeghe
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D006561:Herpes Simplex / Q000188:drug therapy; D006801:Humans; D051379:Mice; D008812:Mice, Hairless; D011817:Rabbits; D051381:Rats; D018139:Simplexvirus / Q000187:drug effects; D014616:Vaccinia virus / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects; D014776:Virus Cultivation
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D003517:Cyclopentanes; D003841:Deoxycytidine; C020235:brivudine; 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; C045202:1-((3-hydroxy)-4-(hydroxymethyl)cyclopentyl)-4-amino-5-(2-bromovinyl)-2(1H)-pyrimidinone; D001973:Bromodeoxyuridine; D003857:Deoxyuridine