| pubmed-article:12852759 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12852759 | lifeskim:mentions | umls-concept:C0164662 | lld:lifeskim |
| pubmed-article:12852759 | lifeskim:mentions | umls-concept:C0376565 | lld:lifeskim |
| pubmed-article:12852759 | lifeskim:mentions | umls-concept:C0806909 | lld:lifeskim |
| pubmed-article:12852759 | lifeskim:mentions | umls-concept:C2346753 | lld:lifeskim |
| pubmed-article:12852759 | lifeskim:mentions | umls-concept:C1707520 | lld:lifeskim |
| pubmed-article:12852759 | lifeskim:mentions | umls-concept:C0243071 | lld:lifeskim |
| pubmed-article:12852759 | pubmed:issue | 15 | lld:pubmed |
| pubmed-article:12852759 | pubmed:dateCreated | 2003-7-10 | lld:pubmed |
| pubmed-article:12852759 | pubmed:abstractText | The synthesis and biological evaluation of a bicyclo[3.1.0]hexene nucleoside designed as a conformational mimic of the anti-HIV agent stavudine (1, D4T) is described. The unsaturated methanocarbocyclic pseudosugar of N-MCD4T (2) was constructed from an iodo-substituted precursor by a DBU-catalyzed olefination reaction. Mitsunobu coupling with N(3)-benzoylthymine afforded the desired target after deprotection. Both D4T and N-MCD4T are in the North (N) hemisphere of the pseudorotational cycle but 70 degrees away from a perfect N (P = 0 degrees ) conformation toward the East and West hemispheres, respectively. Despite this large difference, the double bond reduces the puckering amplitude (nu(max)) of N-MCD4T to 6.81 degrees, and the superposition of both structures showed a RMS deviation of only 0.039 A. The combined structural analysis of P and nu(max) shows that while the value of P may differ substantially, the low nu(max) resolves the differences and becomes the dominant pseudorotational parameter. N-MCD4T is active against HIV-1 and HIV-2 in CEM, MT-2, and MT-4 cells, and while it is somewhat less potent than D4T, it also appears to be less toxic. The triphosphate (N-MCD4TTP) inhibits HIV reverse transcriptase with a 10-fold higher IC(50) than D4TTP. By virtue of its carbocyclic nature, N-MCD4T (2) is a more robust molecule stable to conditions that would cleave D4T. | lld:pubmed |
| pubmed-article:12852759 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12852759 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12852759 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12852759 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12852759 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12852759 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12852759 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12852759 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12852759 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12852759 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12852759 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:12852759 | pubmed:issn | 0022-2623 | lld:pubmed |
| pubmed-article:12852759 | pubmed:author | pubmed-author:MarquezVictor... | lld:pubmed |
| pubmed-article:12852759 | pubmed:author | pubmed-author:MitsuyaHiroak... | lld:pubmed |
| pubmed-article:12852759 | pubmed:author | pubmed-author:BalzariniJanJ | lld:pubmed |
| pubmed-article:12852759 | pubmed:author | pubmed-author:KimHak SungHS | lld:pubmed |
| pubmed-article:12852759 | pubmed:author | pubmed-author:JacobsonKenne... | lld:pubmed |
| pubmed-article:12852759 | pubmed:author | pubmed-author:ChoiYongseokY | lld:pubmed |
| pubmed-article:12852759 | pubmed:author | pubmed-author:HughesStephen... | lld:pubmed |
| pubmed-article:12852759 | pubmed:author | pubmed-author:GeorgeCliffor... | lld:pubmed |
| pubmed-article:12852759 | pubmed:author | pubmed-author:BoyerPaul LPL | lld:pubmed |
| pubmed-article:12852759 | pubmed:author | pubmed-author:BarchiJoseph... | lld:pubmed |
| pubmed-article:12852759 | pubmed:author | pubmed-author:CominMaria... | lld:pubmed |
| pubmed-article:12852759 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12852759 | pubmed:day | 17 | lld:pubmed |
| pubmed-article:12852759 | pubmed:volume | 46 | lld:pubmed |
| pubmed-article:12852759 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12852759 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12852759 | pubmed:pagination | 3292-9 | lld:pubmed |
| pubmed-article:12852759 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
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| pubmed-article:12852759 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:12852759 | pubmed:articleTitle | A conformationally locked analogue of the anti-HIV agent stavudine. An important correlation between pseudorotation and maximum amplitude. | lld:pubmed |
| pubmed-article:12852759 | pubmed:affiliation | Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA. | lld:pubmed |
| pubmed-article:12852759 | pubmed:publicationType | Journal Article | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:12852759 | lld:chembl |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:12852759 | lld:pubmed |
