In vitro antiviral activity of 6-substituted 9-beta-D-ribofuranosylpurine 3', 5'-cyclic phosphates.
A series of twelve recently synthesized 6-substituted derivatives of 9-beta-d-ribofuranosylpurine 3',5'-cyclic phosphate (RPcMP) were evaluated for in vitro antiviral activity, using inhibition of viral cytopathogenic effect as the primary parameter for evaluation. Inhibition of the development of intra- and extracellular virus titer was used as a secondary criterion with certain viruses. Five derivatives were considered to have significant antiviral activity. 6-Hydroxylamino-RPcMP was active against type 1 herpes simplex, cytomegalo-, and vaccinia viruses. 6-Thio-RPcMP was inhibitory to types 1 and 2 herpes simplex, cytomegalo-, vaccinia, and type 3 parainfluenza viruses. The 6-methylthio derivative was active against types 1 and 2 herpes simplex, cytomegalo-, and vaccinia viruses, and types 1A, 2, 8, and 13 rhinoviruses; alteration of this 6-substitution to 6-ethylthio or to 6-benzylthio weakened the herpes- and vaccinia virus activity of the compound, but each continued to have significant antirhinovirus activity. The effect of time of addition of 6-methylthio-RPcMP to type 1 herpes simplex virus-infected cells was determined; the compound was most active when added prior to the virus. Early removal of the compound from the infected cells markedly reduced its antiviral effectiveness.
Sidwell
R W
RW
Huffman
J H
JH
Allen
L B
LB
Meyer
R B
RB
Shuman
D A
DA
Simon
L N
LN
Robins
R K
RK
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy; D006561:Herpes Simplex / Q000188:drug therapy*; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human; D066298:In Vitro Techniques; D007668:Kidney / Q000166:cytology; D011817:Rabbits; D014615:Vaccinia / Q000188:drug therapy; D014709:Vero Cells
D000998:Antiviral Agents; C028539:9 beta-D-ribofuranosylpurine cyclic 3',5'-phosphate; D000242:Cyclic AMP