Synthesis and antiherpetic activity of ( plus or minus )-9-(((Z)-2-(hydroxymethyl)-cyclopropyl)-methyl)guanine and related compounds

A series of analogues of acyclovir and ganciclovir were prepared in which conformational constraints were imposed by incorporation of a cyclopropane ring or unsaturation into the side chain. In addition, several related based-modified compounds were synthesized. These acyclonucleosides were evaluate...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1988-01, Vol.31 (12), p.2304-2315
Main Authors: Ashton, W T, Meurer, L C, Cantone, CL, Field, A K, Hannah, J, Karkas, J D, Liou, R, Patel, G F, Perry, H C
Format: Article
Language:English
Subjects:
herpes simplex virus 2
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Summary:A series of analogues of acyclovir and ganciclovir were prepared in which conformational constraints were imposed by incorporation of a cyclopropane ring or unsaturation into the side chain. In addition, several related based-modified compounds were synthesized. These acyclonucleosides were evaluated for enzymatic phosphorylation and DNA polymerase inhibition in a staggered assay and for inhibitory activity against herpes simplex virus types 1 and 2 in vitro. Certain of the guanine or 8-azaguanine derivatives were good substrates for the viral thymidine kinase and were further converted to triphosphate, but none was a potent inhibitor of the viral DNA polymerase. Nevertheless, one member of this group, ( plus or minus )-9-(((Z)-2-(hydroxymethyl)-cyclopropyl)-methyl)guanine (3a), displayed significant antiherpetic activity in vitro, superior to that of the corresponding cis olefin 4a.
ISSN:0022-2623