Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
1982-4-20
|
| pubmed:abstractText |
The pyrimidine acyclonucleoside 5-fluoro-1-[(2-hydroxyethoxy)methyl]uracil (3) was synthesized as part of a program aimed at the development of new 5-fluorouracil derivatives with fewer side effects and a broader margin of safety. Condensation of 5-fluoro-2,4-bis[(trimethylsilyl)oxy]pyrimidine with 2-acetoxyethyl acetoxymethyl ether (6) in the presence of SnCl4 afforded the acetate ester 7, which on deprotection with NaOMe gave 3 in 50-60% overall yield. The 5-bromo and 5-iodo analogues 10 and 11, respectively, were obtained similarly. Reaction of 5-fluoro-4-(methylthio)-2-[(trimethylsilyl)oxy]pyrimidine with 2-acetoxyethyl acetoxymethyl ether and SnCl4, followed by ammonolysis, yielded 5-fluoro-1-[(2-hydroxyethoxy)methyl]cytosine (12). Deamination of 12 with nitrous acid produced 3, thereby confirming that alkylation of 5-fluoro-2,4-bis[(trimethylsilyl)oxy]pyrimidine had occurred at N1. The ID50 of 3 against L1210 mouse leukemia cells in culture was 1.7 x 10(-5) M, as compared with 1 x 10(-6) M for FU. The 5-fluorocytosine analogue 12 was inactive at up to 1 x 10(-4) M, and the other halogenated derivatives 10 and 11 had no effect even at 1 x 10(-3) M. When 3 was given ip in water to P388 leukemic mice at 400 mg/kg (b.i.d. x 4) or 240 mg/kg (q.d. 1-9), a 75% increase in survival was observed relative to untreated controls, and there was no evidence of any host toxicity.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
24
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1177-81
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading | |
| pubmed:year |
1981
|
| pubmed:articleTitle |
Synthesis and antitumor activity of an acyclonucleoside derivative of 5-fluorouracil.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|