| pubmed-article:19719239 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C0003392 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C0035647 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C0034289 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C0040085 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C0444626 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C0043309 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C1373048 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C1554184 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C1707689 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C0439858 | lld:lifeskim |
| pubmed-article:19719239 | lifeskim:mentions | umls-concept:C0443177 | lld:lifeskim |
| pubmed-article:19719239 | pubmed:issue | 15 | lld:pubmed |
| pubmed-article:19719239 | pubmed:dateCreated | 2009-9-1 | lld:pubmed |
| pubmed-article:19719239 | pubmed:abstractText | N-{4-[(2-Amino-6-ethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)thio]benzoyl}-L-glutamic acid 2 and 13 nonclassical analogues 2a-2m were synthesized as potential dual thymidylate synthase (TS) and dihydrofolate reductase (DHFR) inhibitors and as antitumor agents. The key intermediate in the synthesis was 2-amino-6-ethyl-5-iodothieno[2,3-d]pyrimidin-4(3H)-one, 7, to which various arylthiols were attached at the 5-position. Coupling 8 with L-glutamic acid diethyl ester and saponification afforded 2. X-ray crystal structures of 2 and 1 (the 6-methyl analogue of 2), DHFR, and NADPH showed for the first time that the thieno[2,3-d]pyrimidine ring binds in a "folate" mode. Compound 2 was an excellent dual inhibitor of human TS (IC50 = 54 nM) and human DHFR (IC50 = 19 nM) and afforded nanomolar GI50 values against tumor cells in culture. The 6-ethyl substitution in 2 increases both the potency (by 2-3 orders of magnitude) as well as the spectrum of tumor inhibition in vitro compared to the 6-methyl analogue 1. Some of the nonclassical analogues were potent and selective inhibitors of DHFR from Toxoplasma gondii. | lld:pubmed |
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| pubmed-article:19719239 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19719239 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19719239 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:19719239 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19719239 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:19719239 | pubmed:issn | 1520-4804 | lld:pubmed |
| pubmed-article:19719239 | pubmed:author | pubmed-author:FuY PYP | lld:pubmed |
| pubmed-article:19719239 | pubmed:author | pubmed-author:GangjeeAleemA | lld:pubmed |
| pubmed-article:19719239 | pubmed:author | pubmed-author:KisliukRoy... | lld:pubmed |
| pubmed-article:19719239 | pubmed:author | pubmed-author:CodyVivianV | lld:pubmed |
| pubmed-article:19719239 | pubmed:author | pubmed-author:PaceJimJ | lld:pubmed |
| pubmed-article:19719239 | pubmed:author | pubmed-author:PirainoJennif... | lld:pubmed |
| pubmed-article:19719239 | pubmed:author | pubmed-author:MakinJennifer... | lld:pubmed |
| pubmed-article:19719239 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19719239 | pubmed:day | 13 | lld:pubmed |
| pubmed-article:19719239 | pubmed:volume | 52 | lld:pubmed |
| pubmed-article:19719239 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19719239 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19719239 | pubmed:pagination | 4892-902 | lld:pubmed |
| pubmed-article:19719239 | pubmed:dateRevised | 2011-9-26 | lld:pubmed |
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| pubmed-article:19719239 | pubmed:meshHeading | pubmed-meshheading:19719239... | lld:pubmed |
| pubmed-article:19719239 | pubmed:meshHeading | pubmed-meshheading:19719239... | lld:pubmed |
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| pubmed-article:19719239 | pubmed:meshHeading | pubmed-meshheading:19719239... | lld:pubmed |
| pubmed-article:19719239 | pubmed:meshHeading | pubmed-meshheading:19719239... | lld:pubmed |
| pubmed-article:19719239 | pubmed:meshHeading | pubmed-meshheading:19719239... | lld:pubmed |
| pubmed-article:19719239 | pubmed:meshHeading | pubmed-meshheading:19719239... | lld:pubmed |
| pubmed-article:19719239 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19719239 | pubmed:articleTitle | Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents. | lld:pubmed |
| pubmed-article:19719239 | pubmed:affiliation | Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, Pennsylvania 15282, USA. gangjee@duq.edu | lld:pubmed |
| pubmed-article:19719239 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:19719239 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:19719239 | lld:chembl |
| entrez-gene:573971 | entrezgene:pubmed | pubmed-article:19719239 | lld:entrezgene |
