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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
1989-9-7
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pubmed:abstractText |
N-Hydroxy-alpha-(2-hydroxyethoxy)-1(2H)-pyrimidineacetamides 1-3 were synthesized as potential antitumor agents whose mechanism of action would involve inhibition of ribonucleoside diphosphate reductase (RDPR, EC 1.17.4.1). Acyclonucleoside esters 6-8 were prepared by the stannic chloride catalyzed reaction of methyl chloro[2-(phenylmethoxy)ethoxy]acetate (5) with various silylated pyrimidines, generated in situ from the bases and bis(trimethylsilyl)acetamide. Catalytic didebenzylation of hydroxamate 11 gave 1, while 2 and 3 were synthesized by the reaction of lactones 14 and 22, respectively, with hydroxylamine. In vitro acyclonucleoside hydroxamic acids 1-3 were 3-10-fold less potent than hydroxyurea against calf thymus cytidine diphosphate reductase. 5-Fluorouracil derivative 2 is nearly equipotent with hydroxyurea in inhibiting the growth of HeLa cells, while 1 is a much weaker inhibitor and cytidine derivative 3 is devoid of activity at 200 micrograms/mL.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CDP reductase,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleosides,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleoside Diphosphate Reductase,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleotide Reductases
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1879-85
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:2666666-Antineoplastic Agents,
pubmed-meshheading:2666666-Chemical Phenomena,
pubmed-meshheading:2666666-Chemistry,
pubmed-meshheading:2666666-HeLa Cells,
pubmed-meshheading:2666666-Humans,
pubmed-meshheading:2666666-Hydroxamic Acids,
pubmed-meshheading:2666666-Nucleosides,
pubmed-meshheading:2666666-Ribonucleoside Diphosphate Reductase,
pubmed-meshheading:2666666-Ribonucleotide Reductases
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pubmed:year |
1989
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pubmed:articleTitle |
Synthesis of acyclonucleoside hydroxamic acids as inhibitors of ribonucleotide reductase.
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pubmed:affiliation |
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
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pubmed:publicationType |
Journal Article
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