120386-11-0Relevant articles and documents
Acyclic pyrrolo ?2,3-d!pyrimidine analogs as antiviral agents
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, (2008/06/13)
This invention relates to the use of acyclic substituted pyrrolo?2,3-d!pyrimidine nucleoside analogs in the treatment of viral infections. Such substituted compounds retain antiviral properties present in their parent compounds, yet exhibit significantly decreased levels of cytotoxicity, thereby having therapeutic potential as antiviral agents.
Synthesis, Cytotoxicity, and Antiviral Activity of Certain 7-pyrrolopyrimidine Nucleosides Related to Toyocamycin and Sangivamycin
Gupta, Pranab K.,Nassiri, M. Reza,Coleman, Lisa A.,Wotring, Linda L.,Drach, John C.,Townsend, Leroy B.
, p. 1420 - 1425 (2007/10/02)
A number of 7-pyrrolopyrimidine derivatives related to the nucleoside antibiotics toyocamycin and sangivamycin were prepared and tested for their biological activity.Treatment of the sodium salt of 4-amino-6-bromo-5-cyanopyrrolopyrimidine (1) with (2-acetoxyethoxy)methyl bromide (2) afforded a mixture of 4-amino-6-bromo-5-cyano-7-pyrrolopyrimidine (3) and the corresponding N1 isomer.Debromination of this mixture gave the corresponding 4-amino-5-cyano-7-pyrrolopyrimidine (4) and 4-amino-5-cyano-1-pyrrolopyrimidine (5).Deacetylation of 4 and 5 furnished 4-amino-5-cyano-7-pyrrolopyrimidine (6) and the corresponding N1 isomer (7), respectively.The sites of attachment for the acyclic moiety for 6 and 7 were assigned on the basis of UV spectral studies as well as (13)C NMR spectroscopy.Conventional functional group transformation of 6 provided a number of novel 5-substituted derivatives (8-10), including the sangivamycin derivative 8.The methyl formimidate derivative 10 was converted to the thioamid derivative 11 and the carbohydrazide derivative 12.Compounds 6 and 8-12 were tested for cytotoxicity to L1210 murine leukemic cells in vitro.None of these compounds caused significant inhibition of cell growth.Evaluation of compounds 4 and 6-12 for activity against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) revealed that only the thioamide (11) was active.It inhibited HCMV but not HSV-1 at concentrations producing only slight cytotoxicity in the human foreskin fibroblasts (HFF cells) and KB cells.