Linked Life Data

2175356

Source:http://linkedlifedata.com/resource/pubmed/id/2175356

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1991-1-29
pubmed:abstractText
Protection of the 3'- and 5'-hydroxyl groups of the nucleoside antibiotic toyocamycin (1) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane was followed by (trifluoromethyl)sulfonylation of the 2'-hydroxyl group. A displacement of the resulting triflate ester moiety with lithium chloride, lithium bromide, sodium iodide, and lithium azide in hexamethylphosphoramide was followed by a removal of the disilyl moiety with tetra-n-butylammonium fluoride to afford the appropriate (2'-deoxy-2'-substituted-arabinofuranosyl)toyocamycin analogues 6a-d. Hydrolysis of the carbonitrile moieties of 6a-d with hydrogen peroxide gave the corresponding sangivamycin analogues (7a-d). A reduction of the azido moiety of 6a and 7a with 1,3-propanedithiol furnished the corresponding amino derivatives (6e and 7e). The antiproliferative activity of 6a-e and 7a-e was evaluated in L1210 cell cultures. None of these compounds caused significant inhibition of cell growth. Evaluation of these compounds for antiviral activity showed that all the toyocamycin analogues were active against human CMV, but of the sangivamycin analogues, only (2'-deoxy-2'-azidoarabinosyl)sangivamycin (7a) was active against this virus. None of the compounds were active against HSV-1 or HSV-2. (2'-Deoxy-2'-aminoarabinofuranosyl)toyocamycin (6e) was studied more extensively and showed some separation between antiviral activity and cytotoxicity as measured by effects on DNA synthesis, cell growth, and cell-plating efficiency. Although 6e also was active against murine CMV in vitro, it was not active against this virus in infected mice. We conclude that arabinosylpyrrolopyrimidines have potential as antivirals, but no members of the current series are potent enough to show significant activity in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3160-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Arabinofuranosylpyrrolo[2,3-d]pyrimidines as potential agents for human cytomegalovirus infections.
pubmed:affiliation
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't